Ian Gotlib

All Publications

• Corrigendum to "Mode of delivery predicts postpartum maternal leukocyte telomere length" [Eur. J. Obstetr. Gynecol. Reprod. Biol. 300 (2024) 224-229]. European journal of obstetrics, gynecology, and reproductive biology Panelli, D. M., Mayo, J. A., Wong, R. J., Becker, M., Feyaerts, D., Marić, I., Wu, E., Gotlib, I. H., Gaudillière, B., Aghaeepour, N., Druzin, M. L., Stevenson, D. K., Shaw, G. M., Bianco, K. 2024; 304: 35

  View details for DOI 10.1016/j.ejogrb.2024.11.017

  View details for PubMedID 39561615

• Exposure to diesel-related particulate matter, cortisol stress responsivity, and depressive symptoms in adolescents. Psychoneuroendocrinology Uy, J. P., Shin, K., Buthmann, J. L., Kircanski, K., LeMoult, J., Berens, A. E., Gotlib, I. H. 2024; 171: 107214

  Abstract

  Exposure to air pollution is associated with higher risk for psychopathology; however, the mechanisms underlying this association are not clear. Dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis in response to stress has been implicated in depression. Here, we estimated annual exposure to particulate matter (PM) from diesel emissions in 170 9- to 15-year-old adolescents (56 % female) using their residential addresses and data from nearby monitoring sites. We obtained salivary cortisol samples from participants while they completed a social stress task and calculated area under the curve with respect to ground (AUCg) and with respect to increase (AUCi) in order to assess cortisol responsivity during stress. Participants also reported on their depressive symptoms and sleep disturbances. Greater exposure to diesel PM was associated with lower cortisol output (AUCg) during stress, which was associated with higher depressive symptoms, particularly for adolescents with more sleep disturbances. Importantly, these effects were independent of household and neighborhood socioeconomic disadvantage and exposure to early adversity. Thus, HPA-axis dysfunction may be one mechanism through which environmental pollutants affect adolescents' mental health.

  View details for DOI 10.1016/j.psyneuen.2024.107214

  View details for PubMedID 39426039

• Predicting Task Activation Maps from Resting-State Functional Connectivity using Deep Learning. bioRxiv : the preprint server for biology Madsen, S. J., Uddin, L. Q., Mumford, J. A., Barch, D. M., Fair, D. A., Gotlib, I. H., Poldrack, R. A., Kuceyeski, A., Saggar, M. 2024

  Abstract

  Recent work has shown that deep learning is a powerful tool for predicting brain activation patterns evoked through various tasks using resting state features. We replicate and improve upon this recent work to introduce two models, BrainSERF and BrainSurfGCN, that perform at least as well as the state-of-the-art while greatly reducing memory and computational footprints. Our performance analysis observed that low predictability was associated with a possible lack of task engagement derived from behavioral performance. Furthermore, a deficiency in model performance was also observed for closely matched task contrasts, likely due to high individual variability confirmed by low test-retest reliability. Overall, we successfully replicate recently developed deep learning architecture and provide scalable models for further research.

  View details for DOI 10.1101/2024.09.10.612309

  View details for PubMedID 39314460

  View details for PubMedCentralID PMC11419026

• Mind-wandering in daily life in depressed individuals: An experience sampling study. Journal of affective disorders Welhaf, M. S., Mata, J., Jaeggi, S. M., Buschkuehl, M., Jonides, J., Gotlib, I. H., Thompson, R. J. 2024

  Abstract

  BACKGROUND: A diagnostic criterion for Major Depressive Disorder (MDD) is difficulty concentrating and increased distractibility. One form of distraction that occurs in everyday life is mind-wandering. The current study aims to test how individuals with MDD and healthy controls differ in their mind-wandering in everyday life.METHODS: Adults diagnosed with MDD (n = 53) and healthy controls (n = 53) completed a week of experience sampling, with prompts administered up to eight times per day. At each prompt, participants reported the occurrence and characteristics of their mind-wandering. They also reported levels of momentary negative affect (NA), positive affect (PA), and rumination.RESULTS: MDD participants reported mind-wandering almost twice as often as healthy control participants. Compared to healthy participants, MDD participants rated their mind-wandering as more negative, but did not differ in terms of temporal orientation. Higher NA and lower PA predicted mind-wandering in the MDD group but not healthy controls, even after controlling for rumination. Time-lagged analyses revealed that current mind-wandering predicted future levels of PA in MDD participants but not in healthy controls; in contrast, current NA and PA did not predict future mind-wandering.LIMITATIONS: Limitations include our examination of specific forms of mind-wandering (i.e., we did not sample the full spectrum of this construct).CONCLUSIONS: Individuals with MDD frequently report engaging in mind-wandering in everyday life, and this appears to be coupled with affect. Mind-wandering may have maladaptive effects in MDD and could serve as a target for intervention.

  View details for DOI 10.1016/j.jad.2024.08.111

  View details for PubMedID 39181165

• Mode of delivery predicts postpartum maternal leukocyte telomere length. European journal of obstetrics, gynecology, and reproductive biology Panelli, D. M., Mayo, J. A., Wong, R. J., Becker, M., Feyaerts, D., Marić, I., Wu, E., Gotlib, I. H., Gaudillière, B., Aghaeepour, N., Druzin, M. L., Stevenson, D. K., Shaw, G. M., Bianco, K. 2024; 300: 224-229

  Abstract

  Recent studies have suggested that pregnancy accelerates biologic aging, yet little is known about how biomarkers of aging are affected by events during the peripartum period. Given that immune shifts are known to occur following surgery, we explored the relation between mode of delivery and postpartum maternal leukocyte telomere length (LTL), a marker of biologic aging.Postpartum maternal blood samples were obtained from a prospective cohort of term, singleton livebirths without hypertensive disorders or peripartum infections between 2012 and 2018. The primary outcome was postpartum LTLs from one blood sample drawn between postpartum week 1 and up to 6 months postpartum, measured from thawed frozen peripheral blood mononuclear cells using quantitative PCR in basepairs (bp). Multivariable linear regression models compared LTLs between vaginal versus cesarean births, adjusting for age, body mass index, and nulliparity as potential confounders. Analyses were conducted in two mutually exclusive groups: those with LTL measured postpartum week 1 and those measured up to 6 months postpartum. Secondarily, we compared multiomics by mode of delivery using machine-learning methods to evaluate whether other biologic changes occurred following cesarean. These included transcriptomics, metabolomics, microbiomics, immunomics, and proteomics (serum and plasma).Of 67 included people, 50 (74.6 %) had vaginal and 17 (25.4 %) had cesarean births. LTLs were significantly shorter after cesarean in postpartum week 1 (5755.2 bp cesarean versus 6267.8 bp vaginal, p = 0.01) as well as in the later draws (5586.6 versus 5945.6 bp, p = 0.04). After adjusting for confounders, these differences persisted in both week 1 (adjusted beta -496.1, 95 % confidence interval [CI] -891.1, -101.1, p = 0.01) and beyond (adjusted beta -396.8; 95 % CI -727.2, -66.4. p = 0.02). Among the 15 participants who also had complete postpartum multiomics data available, there were predictive signatures of vaginal versus cesarean births in transcriptomics (cell-free [cf]RNA), metabolomics, microbiomics, and proteomics that did not persist after false discovery correction.Maternal LTLs in postpartum week 1 were nearly 500 bp shorter following cesarean. This difference persisted several weeks postpartum, even though other markers of inflammation had normalized. Mode of delivery should be considered in any analyses of postpartum LTLs and further investigation into this phenomenon is warranted.

  View details for DOI 10.1016/j.ejogrb.2024.07.026

  View details for PubMedID 39032311

• Effects of Pollution Burden on Neural Function During Implicit Emotion Regulation and Longitudinal Changes in Depressive Symptoms in Adolescents. Biological psychiatry global open science Uy, J. P., Yuan, J. P., Colich, N. L., Gotlib, I. H. 2024; 4 (4): 100322

  Abstract

  Exposure to environmental pollutants early in life has been associated with increased prevalence and severity of depression in adolescents; however, the neurobiological mechanisms underlying this association are not well understood. In the current longitudinal study, we investigated whether pollution burden in early adolescence (9-13 years) was associated with altered brain activation and connectivity during implicit emotion regulation and changes in depressive symptoms across adolescence.One hundred forty-five participants (n = 87 female; 9-13 years) provided residential addresses, from which we determined their relative pollution burden at the census tract level, and performed an implicit affective regulation task in the scanner. Participants also completed questionnaires assessing depressive symptoms at 3 time points, each approximately 2 years apart, from which we calculated within-person slopes of depressive symptoms. We conducted whole-brain activation and connectivity analyses to examine whether pollution burden was associated with alterations in brain function during implicit emotion regulation of positively and negatively valenced stimuli and how these effects were related to slopes of depressive symptoms across adolescence.Greater pollution burden was associated with greater bilateral medial prefrontal cortex activation and stronger bilateral medial prefrontal cortex connectivity with regions within the default mode network (e.g., temporoparietal junction, posterior cingulate cortex, precuneus) during implicit regulation of negative emotions, which was associated with greater increases in depressive symptoms across adolescence in those exposed to higher pollution burden.Adolescents living in communities characterized by greater pollution burden showed altered default mode network functioning during implicit regulation of negative emotions that was associated with increases in depressive symptoms across adolescence.

  View details for DOI 10.1016/j.bpsgos.2024.100322

  View details for PubMedID 38957313

  View details for PubMedCentralID PMC11217611

• Effects of Pollution Burden on Neural Function During Implicit Emotion Regulation and Longitudinal Changes in Depressive Symptoms in Adolescents BIOLOGICAL PSYCHIATRY: GLOBAL OPEN SCIENCE Uy, J. P., Yuan, J. P., Colich, N. L., Gotlib, I. H. 2024; 4 (4)

  View details for DOI 10.1016/j.bpsgos.2024.100322

  View details for Web of Science ID 001251558600001

• Personalized brain circuit scores identify clinically distinct biotypes in depression and anxiety. Nature medicine Tozzi, L., Zhang, X., Pines, A., Olmsted, A. M., Zhai, E. S., Anene, E. T., Chesnut, M., Holt-Gosselin, B., Chang, S., Stetz, P. C., Ramirez, C. A., Hack, L. M., Korgaonkar, M. S., Wintermark, M., Gotlib, I. H., Ma, J., Williams, L. M. 2024

  Abstract

  There is an urgent need to derive quantitative measures based on coherent neurobiological dysfunctions or 'biotypes' to enable stratification of patients with depression and anxiety. We used task-free and task-evoked data from a standardized functional magnetic resonance imaging protocol conducted across multiple studies in patients with depression and anxiety when treatment free (n = 801) and after randomization to pharmacotherapy or behavioral therapy (n = 250). From these patients, we derived personalized and interpretable scores of brain circuit dysfunction grounded in a theoretical taxonomy. Participants were subdivided into six biotypes defined by distinct profiles of intrinsic task-free functional connectivity within the default mode, salience and frontoparietal attention circuits, and of activation and connectivity within frontal and subcortical regions elicited by emotional and cognitive tasks. The six biotypes showed consistency with our theoretical taxonomy and were distinguished by symptoms, behavioral performance on general and emotional cognitive computerized tests, and response to pharmacotherapy as well as behavioral therapy. Our results provide a new, theory-driven, clinically validated and interpretable quantitative method to parse the biological heterogeneity of depression and anxiety. Thus, they represent a promising approach to advance precision clinical care in psychiatry.

  View details for DOI 10.1038/s41591-024-03057-9

  View details for PubMedID 38886626

  View details for PubMedCentralID 7653736

• Threat- and Reward-Related Brain Circuitry, Perceived Stress, and Anxiety in Adolescents During the COVID-19 Pandemic: A Longitudinal Investigation. Social cognitive and affective neuroscience Borchers, L. R., Gifuni, A. J., Ho, T. C., Kirshenbaum, J. S., Gotlib, I. H. 2024

  Abstract

  The COVID-19 pandemic has been related to heightened anxiety in adolescents. The basolateral amygdala (BLA) and the nucleus accumbens (NAcc) have been implicated in response to stress and may contribute to anxiety. The role of threat- and reward-related circuitry in adolescent anxiety during the COVID-19 pandemic, however, is not clear. Ninety-nine adolescents underwent resting-state fMRI approximately one year before the pandemic. Following shelter-in-place orders, adolescents reported their perceived stress and, one month later, their anxiety. Generalized multivariate analyses identified BLA and NAcc seed-based whole-brain connectivity maps with perceived stress. We examined associations between seed-based connectivity in significant clusters and subsequent anxiety. Perceived stress was associated with bilateral BLA and NAcc connectivity across distributed clusters that included prefrontal, limbic, temporal, and cerebellar regions. Several NAcc connectivity clusters located in ventromedial prefrontal, parahippocampal, and temporal cortices were positively associated with anxiety; whereas NAcc connectivity with the inferior frontal gyrus was negatively associated. BLA connectivity was not associated with anxiety. These results underscore the integrative role of the NAcc in responding to acute stressors and its relation to anxiety in adolescents. Elucidating the involvement of subcortical-cortical circuitry in adolescents' capacity to respond adaptively to environmental challenges can inform treatment approaches for anxiety-related disorders.

  View details for DOI 10.1093/scan/nsae040

  View details for PubMedID 38874967

• Task-Rest Reconfiguration Efficiency of the Reward Network Across Adolescence and its Association With Early Life Stress and Depressive Symptoms. Journal of the American Academy of Child and Adolescent Psychiatry Lee, Y., Yuan, J. P., Winkler, A. M., Kircanski, K., Pine, D. S., Gotlib, I. H. 2024

  Abstract

  Adolescents face significant changes in many domains of their daily lives that require them to flexibly adapt to changing environmental demands. To shift efficiently among various goals, adolescents must reconfigure their brains, disengaging from previous tasks and engaging in new activities.To examine this reconfiguration, we obtained resting-state and task-based fMRI scans in a community sample of 164 adolescents. We assessed the similarity of functional connectivity (FC) of the reward network between resting state and a reward processing state, indexing the degree of reward network reconfiguration required to meet task demands. Given research documenting relations among reward network function, early life stress (ELS), and adolescent depression, we examined the association of reconfiguration efficiency with age across adolescence, the moderating effect of ELS on this association, and the relation between reconfiguration efficiency and depressive symptoms.We found that older adolescents showed greater reconfiguration efficiency than younger adolescents and, further, that this age-related association was moderated by the experience of ELS.These findings suggest that reconfiguration efficiency of the reward network increases over adolescence, a developmental pattern that is attenuated in adolescents exposed to severe ELS. In addition, even after controlling for the effects of age and exposure to ELS, adolescents with higher levels of depressive symptoms exhibited greater reconfiguration efficiency, suggesting that they have brain states at rest that are more strongly optimized for reward processing than do asymptomatic youth.

  View details for DOI 10.1016/j.jaac.2024.04.018

  View details for PubMedID 38878818

• Principal component analysis as an efficient method for capturing multivariate brain signatures of complex disorders-ENIGMA study in people with bipolar disorders and obesity. Human brain mapping McWhinney, S. R., Hlinka, J., Bakstein, E., Dietze, L. M., Corkum, E. L., Abé, C., Alda, M., Alexander, N., Benedetti, F., Berk, M., Bøen, E., Bonnekoh, L. M., Boye, B., Brosch, K., Canales-Rodríguez, E. J., Cannon, D. M., Dannlowski, U., Demro, C., Diaz-Zuluaga, A., Elvsåshagen, T., Eyler, L. T., Fortea, L., Fullerton, J. M., Goltermann, J., Gotlib, I. H., Grotegerd, D., Haarman, B., Hahn, T., Howells, F. M., Jamalabadi, H., Jansen, A., Kircher, T., Klahn, A. L., Kuplicki, R., Lahud, E., Landén, M., Leehr, E. J., Lopez-Jaramillo, C., Mackey, S., Malt, U., Martyn, F., Mazza, E., McDonald, C., McPhilemy, G., Meier, S., Meinert, S., Melloni, E., Mitchell, P. B., Nabulsi, L., Nenadić, I., Nitsch, R., Opel, N., Ophoff, R. A., Ortuño, M., Overs, B. J., Pineda-Zapata, J., Pomarol-Clotet, E., Radua, J., Repple, J., Roberts, G., Rodriguez-Cano, E., Sacchet, M. D., Salvador, R., Savitz, J., Scheffler, F., Schofield, P. R., Schürmeyer, N., Shen, C., Sim, K., Sponheim, S. R., Stein, D. J., Stein, F., Straube, B., Suo, C., Temmingh, H., Teutenberg, L., Thomas-Odenthal, F., Thomopoulos, S. I., Urosevic, S., Usemann, P., van Haren, N. E., Vargas, C., Vieta, E., Vilajosana, E., Vreeker, A., Winter, N. R., Yatham, L. N., Thompson, P. M., Andreassen, O. A., Ching, C. R., Hajek, T. 2024; 45 (8): e26682

  Abstract

  Multivariate techniques better fit the anatomy of complex neuropsychiatric disorders which are characterized not by alterations in a single region, but rather by variations across distributed brain networks. Here, we used principal component analysis (PCA) to identify patterns of covariance across brain regions and relate them to clinical and demographic variables in a large generalizable dataset of individuals with bipolar disorders and controls. We then compared performance of PCA and clustering on identical sample to identify which methodology was better in capturing links between brain and clinical measures. Using data from the ENIGMA-BD working group, we investigated T1-weighted structural MRI data from 2436 participants with BD and healthy controls, and applied PCA to cortical thickness and surface area measures. We then studied the association of principal components with clinical and demographic variables using mixed regression models. We compared the PCA model with our prior clustering analyses of the same data and also tested it in a replication sample of 327 participants with BD or schizophrenia and healthy controls. The first principal component, which indexed a greater cortical thickness across all 68 cortical regions, was negatively associated with BD, BMI, antipsychotic medications, and age and was positively associated with Li treatment. PCA demonstrated superior goodness of fit to clustering when predicting diagnosis and BMI. Moreover, applying the PCA model to the replication sample yielded significant differences in cortical thickness between healthy controls and individuals with BD or schizophrenia. Cortical thickness in the same widespread regional network as determined by PCA was negatively associated with different clinical and demographic variables, including diagnosis, age, BMI, and treatment with antipsychotic medications or lithium. PCA outperformed clustering and provided an easy-to-use and interpret method to study multivariate associations between brain structure and system-level variables. PRACTITIONER POINTS: In this study of 2770 Individuals, we confirmed that cortical thickness in widespread regional networks as determined by principal component analysis (PCA) was negatively associated with relevant clinical and demographic variables, including diagnosis, age, BMI, and treatment with antipsychotic medications or lithium. Significant associations of many different system-level variables with the same brain network suggest a lack of one-to-one mapping of individual clinical and demographic factors to specific patterns of brain changes. PCA outperformed clustering analysis in the same data set when predicting group or BMI, providing a superior method for studying multivariate associations between brain structure and system-level variables.

  View details for DOI 10.1002/hbm.26682

  View details for PubMedID 38825977

  View details for PubMedCentralID PMC11144951

• Comparison of Lasso and Stepwise Regression in Psychological Data METHODOLOGY-EUROPEAN JOURNAL OF RESEARCH METHODS FOR THE BEHAVIORAL AND SOCIAL SCIENCES Zhou, D., Chahal, R., Gotlib, I. H., Liu, S. 2024; 20 (2): 121-143

  View details for DOI 10.5964/meth.11523

  View details for Web of Science ID 001261728200003

• Socioeconomic Disadvantage Moderates the Association of Systemic Inflammation with Amygdala Volume in Adolescents Over a Two-Year Interval: An Exploratory Study. Biological psychiatry. Cognitive neuroscience and neuroimaging Yuan, J. P., Jaeger, E. L., Coury, S. M., Uy, J. P., Buthmann, J. L., Ho, T. C., Gotlib, I. H. 2024

  Abstract

  Research has demonstrated an association between elevated systemic inflammation and changes in brain function. Affective areas of the brain involved in processing threat (e.g., amygdala) and reward (e.g., nucleus accumbens [NAcc]) appear to be sensitive to inflammation. Early life stress (ELS), such as experiencing low socioeconomic status (SES), may also potentiate this association, but relevant evidence has come primarily from cross-sectional studies of brain function. It is unclear whether similar associations are present between ELS, inflammation, and brain structure, particularly in typically developing populations.We recruited and assessed 50 adolescents (31F/19M) from the community (M±SD age=15.5±1.1; range=13.1-17.5 years ) and in exploratory analyses examined whether changes in C-reactive protein (ΔCRP) from blood spots predict changes in gray matter volumes (ΔGMV) in the bilateral amygdala and NAcc over a two-year period. We also investigated whether experiencing ELS, operationalized using a comprehensive composite score of SES disadvantage at the family and neighborhood levels, significantly moderated the association between ΔCRP and ΔGMV.We found that ΔCRP was negatively associated with ΔAmygdala GMV (i.e. increasing CRP levels were associated with decreasing amygdala volume; β=-0.84; p=0.012). This effect was stronger in youth who experienced greater SES disadvantage (β=-0.56; p=0.025).These findings suggest that increases in systemic inflammation are associated with reductions in amygdala GMV in adolescents, potentially signaling accelerated maturation, and that these neuroimmune processes are compounded in adolescents who experienced greater SES disadvantage. Our findings are consistent with theoretical frameworks of neuroimmune associations and suggest they may influence adolescent neurodevelopment.

  View details for DOI 10.1016/j.bpsc.2024.05.002

  View details for PubMedID 38815859

• Faster pace of hippocampal growth mediates the association between perinatal adversity and childhood depression. Developmental cognitive neuroscience Miller, J. G., Gluckman, P. D., Fortier, M. V., Chong, Y. S., Meaney, M. J., Tan, A. P., Gotlib, I. H. 2024; 67: 101392

  Abstract

  Early life adversity has been posited to influence the pace of structural neurodevelopment. Most research, however, has relied on cross-sectional data, which do not reveal whether the pace of neurodevelopmental change is accelerated or slowed following early exposures. In a birth cohort study that included neuroimaging data obtained at 4.5, 6, and 7.5 years of age (N = 784), we examined associations among a cumulative measure of perinatal adversity relative to resources, nonlinear trajectories of hippocampal and amygdala volume, and children's subsequent depressive symptoms at 8.5 years of age. Greater adversity was associated with reduced bilateral hippocampal body volume in early childhood, but also to faster growth in the right hippocampal body across childhood. Further, the association between adversity and childhood depressive symptoms was mediated by faster hippocampal body growth. These findings suggest that perinatal adversity is biologically embedded in hippocampal structure development, including an accelerated pace of change in the right hippocampal body that is implicated in children's psychopathology risk. In addition, our findings suggest that reduced hippocampal volume is not inconsistent with accelerated hippocampal change; these aspects of structural development may typically co-occur, as smaller regional volumes in early childhood were associated with faster growth across childhood.

  View details for DOI 10.1016/j.dcn.2024.101392

  View details for PubMedID 38761439

• Common and Distinct Patterns of Neural Activation Between Major Depressive Disorder and Generalized Anxiety Disorder: A Comparison of Meta-Analytic Findings From Functional Magnetic Resonance Imaging Studies Kahlon, S. K., Lindlahr, C., Klassen, A. M., Baten, C., Ali, Z., Shepherd, J. H., Zamora, G., Saravia, S., Pritchard, E., Jordan, J., Maly, G., Duran, M., Santos, S. L., Woo, E., Nimarko, A. F., Hedges, D. H., Hamilton, P., Sacchet, M. D., Gotlib, I. H., Miller, C. H. ELSEVIER SCIENCE INC. 2024: S125

  View details for Web of Science ID 001282811900289

• Meta-Analysis of Functional Magnetic Resonance Imaging Studies Reveals Abnormal Patterns of Neural Activation in Panic Disorder and Agoraphobia Baten, C., Klassen, A. M., Zamora, G., Shepherd, J. H., Badawia, A., Kailay, A., Leung, C., Ranjithprabhu, A., Sahota, J., Saravia, S., Miller, J. A., Woo, E., Gotlib, I. H., Hamilton, P., Sacchet, M. D., Hedges, D. W., Miller, C. H. ELSEVIER SCIENCE INC. 2024: S123-S124

  View details for Web of Science ID 001282811900285

• Nucleus Accumbens Volume Mediates the Association Between Prenatal Adversity and Attention Problems in Youth Antonacci, C., Buthmann, J. L., Borchers, L., Tan, A., Meaney, M., Gotlib, I. H. ELSEVIER SCIENCE INC. 2024: S132-S133

  View details for Web of Science ID 001282811900306

• The cortisol/DHEA ratio mediates the association between early life stress and externalizing problems in adolescent boys. Psychoneuroendocrinology Lee, Y., Donahue, G. Z., Buthmann, J. L., Uy, J. P., Gotlib, I. H. 2024; 165: 107034

  Abstract

  Despite evidence that early life stress (ELS) can influence the functioning of the hypothalamic-pituitary-adrenal (HPA) axis and increase maladaptive behaviors in adolescence, less attention has been paid to the role of the coordinated effects of the two primary adrenal hormones, cortisol and dehydroepiandrosterone (DHEA), in these associations.138 typically developing adolescents (76 females) reported the stressful events experienced during childhood and early adolescence across 30 domains. Two years later we assessed levels of externalizing problems and obtained salivary levels of cortisol and DHEA. Using causal moderated mediation analyses, we examined whether the ratio of cortisol to DHEA (CD ratio) mediates the association between ELS and subsequent externalizing problems.We found that ELS is associated with both a lower CD ratio and more externalizing problems. Importantly, a lower CD ratio mediated the association between ELS and externalizing problems in boys.An imbalance in adrenal hormones may be a mechanism through which ELS leads to an increase in externalizing problems in adolescent boys. These findings underscore the utility of using the CD ratio to index HPA-axis functioning.

  View details for DOI 10.1016/j.psyneuen.2024.107034

  View details for PubMedID 38554595

• The growing interdisciplinarity of developmental psychopathology: Implications for science and training. Development and psychopathology Gotlib, I. H., Buthmann, J. L., Uy, J. P. 2024: 1-11

  Abstract

  The field of developmental psychopathology has grown exponentially over the past decades, and has become increasingly multifaceted. The initial focus on understanding abnormal child psychology has broadened to the study of the origins of psychopathology, with the goals of preventing and alleviating disorder and promoting healthy development. In this paper, we discuss how technological advances and global events have expanded the questions that researchers in developmental psychopathology can address. We do so by describing a longitudinal study that we have been conducting for the past dozen years. We originally planned to examine the effects of early adversity on trajectories of brain development, endocrine function, and depressive symptoms across puberty; it has since become an interdisciplinary study encompassing diverse domains like inflammation, sleep, biological aging, the environment, and child functioning post-pandemic, that we believe will advance our understanding of neurobehavioral development. This increase in the breadth in our study emerged from an expansion of the field; we encourage researchers to embrace these dynamic changes. In this context, we discuss challenges, opportunities, and institutional changes related to the growing interdisciplinarity of the field with respect to training the next generation of investigators to mitigate the burden of mental illness in youth.

  View details for DOI 10.1017/S0954579424000580

  View details for PubMedID 38516854

• A Data-Driven Latent Variable Approach to Validating the Research Domain Criteria Framework. bioRxiv : the preprint server for biology Quah, S. K., Jo, B., Geniesse, C., Uddin, L. Q., Mumford, J. A., Barch, D. M., Fair, D. A., Gotlib, I. H., Poldrack, R. A., Saggar, M. 2024

  Abstract

  Despite the widespread use of the Research Domain Criteria (RDoC) framework in psychiatry and neuroscience, recent studies suggest that the RDoC is insufficiently specific or excessively broad relative to the underlying brain circuitry it seeks to elucidate. To address these concerns of the RDoC framework, our study employed a latent variable approach, specifically utilizing bifactor analysis. We examined a total of 84 whole-brain task-based fMRI (tfMRI) activation maps from 19 studies with a total of 6,192 participants. Within this set of 84 maps, a curated subset of 37 maps with a balanced representation of RDoC domains constituted the training set of our analysis, and the remaining held-out maps formed the internal validation set. External validation was performed with 36 peak coordinate activation maps from Neurosynth, using terms of RDoC constructs as seeds for topic meta-analysis. Our results indicate that a bifactor model with a task-general domain and splitting the cognitive systems domain into sub-domains better fits the current corpus of tfMRI data than the current RDoC framework. Our data-driven validation supports revising the RDoC framework to accurately reflect underlying brain circuitry.

  View details for DOI 10.1101/2024.01.31.577486

  View details for PubMedID 38559071

• Intracranial recordings of the human orbitofrontal cortical activity during self-referential episodic and valenced self-judgments. The Journal of neuroscience : the official journal of the Society for Neuroscience Iravani, B., Kaboodvand, N., Stieger, J. R., Liang, E. Y., Lusk, Z., Fransson, P., Deutsch, G. K., Gotlib, I. H., Parvizi, J. 2024

  Abstract

  We recorded directly from the orbital (oPFC) and ventromedial (vmPFC) subregions of the orbitofrontal cortex (OFC) in 22 (9 female, 13 male) epilepsy patients undergoing intracranial electroencephalography (iEEG) monitoring during an experimental task in which the participants judged the accuracy of self-referential autobiographical statements as well as valenced self-judgments. We found significantly increased high-frequency activity (HFA) in about 13% of oPFC sites (10/18 subjects) and 16% of vmPFC sites (4/12 subjects) during both of these self-referential thought processes, with the HFA power being modulated by the content of self-referential stimuli. The location of these activated sites corresponded with the location of fMRI-identified limbic network. Furthermore, the onset of HFA in the vmPFC was significantly earlier than in the oPFC in all patients with simultaneous recordings in both regions. In 11 patients with available depression scores from comprehensive neuropsychological assessments, we documented diminished HFA activity in the OFC during positive self-judgment trials among individuals with higher depression scores; responses during negative self-judgment trials were not related to the patients' depression scores. Our findings provide new temporal and anatomical information about the mode of engagement in two important subregions of the OFC during autobiographical memory and self-judgment conditions. Our findings from the OFC support the hypothesis that diminished brain activity during positive self-evaluations, rather than heightened activity during negative self-evaluations, plays a key role in the pathophysiology of depression.Significance Statement In direct recordings from the human brain, we observed significant responses characterized by high-frequency activity, aka high gamma, in distinct populations of the orbital (oPFC) and ventromedial (vmPFC) regions of the orbitofrontal cortex (OFC) - corresponding to the location of the resting state limbic network and to a lesser extent default mode network - when human subjects were engaged in self-referential episodic memory retrieval and self-trait judgments. Notably, simultaneous recordings across the two OFC regions in the same individuals revealed earlier activations in vmPFC than oPFC, indicating that the two subregions are involved in different stages of self-referential thought processes. Lastly, in individuals with high depressive symptoms, the OFC responses were significantly reduced during positive self-judgments but not heightened during negative self-evaluations.

  View details for DOI 10.1523/JNEUROSCI.1634-23.2024

  View details for PubMedID 38316564

• Large-scale proteomics in the first trimester of pregnancy predict psychopathology and temperament in preschool children: an exploratory study. Journal of child psychology and psychiatry, and allied disciplines Buthmann, J. L., Miller, J. G., Aghaeepour, N., King, L. S., Stevenson, D. K., Shaw, G. M., Wong, R. J., Gotlib, I. H. 2024

  Abstract

  Understanding the prenatal origins of children's psychopathology is a fundamental goal in developmental and clinical science. Recent research suggests that inflammation during pregnancy can trigger a cascade of fetal programming changes that contribute to vulnerability for the emergence of psychopathology. Most studies, however, have focused on a handful of proinflammatory cytokines and have not explored a range of prenatal biological pathways that may be involved in increasing postnatal risk for emotional and behavioral difficulties.Using extreme gradient boosted machine learning models, we explored large-scale proteomics, considering over 1,000 proteins from first trimester blood samples, to predict behavior in early childhood. Mothers reported on their 3- to 5-year-old children's (N = 89, 51% female) temperament (Child Behavior Questionnaire) and psychopathology (Child Behavior Checklist).We found that machine learning models of prenatal proteomics predict 5%-10% of the variance in children's sadness, perceptual sensitivity, attention problems, and emotional reactivity. Enrichment analyses identified immune function, nervous system development, and cell signaling pathways as being particularly important in predicting children's outcomes.Our findings, though exploratory, suggest processes in early pregnancy that are related to functioning in early childhood. Predictive features included far more proteins than have been considered in prior work. Specifically, proteins implicated in inflammation, in the development of the central nervous system, and in key cell-signaling pathways were enriched in relation to child temperament and psychopathology measures.

  View details for DOI 10.1111/jcpp.13948

  View details for PubMedID 38287782

• Sex-Specific Vulnerability to Externalizing Problems: Sensitivity to Early Stress and Nucleus Accumbens Activation Over Adolescence. Biological psychiatry Borchers, L. R., Yuan, J. P., Leong, J. K., Jo, B., Chahal, R., Ryu, J., Nam, A., Coury, S. M., Gotlib, I. H. 2024

  Abstract

  Exposure and sensitivity to early life stress (ELS) are related to increased risk for psychopathology in adolescence. While cross-sectional studies have reported blunted nucleus accumbens (NAcc) activation in the context of these associations, researchers have not yet assessed the effects of ELS on developmental trajectories of activation. We examined whether trajectories are affected by stress and the moderating role of biological sex in predicting vulnerability to symptoms of psychopathology.Adolescents (n=173) completed three assessments at two-year intervals across puberty (ages 9-18 years). At baseline we assessed objective ELS and stress sensitivity using the Traumatic Events Screening Inventory for Children. At all timepoints we assessed NAcc activation using the Monetary Incentive Delay task and externalizing, internalizing, and total problems using the Youth Self-Report. We correlated NAcc trajectories (extracted using linear mixed effects models) with ELS and stress sensitivity, and conducted multivariate regression analysis to examine the interaction of NAcc trajectories and biological sex in predicting symptoms of psychopathology.Symptoms increased over adolescence. Stress sensitivity, but not objective ELS, was associated with decreasing trajectories of NAcc activation. Biological sex interacted with NAcc trajectories to predict psychopathology: boys, but not girls, with decreasing NAcc activation had more severe externalizing problems in adolescence. These findings were replicated in the putamen and caudate but not in the medial prefrontal cortex or control brain regions.NAcc activation may be a sex-specific marker of externalizing problems in adolescence. Efforts to reduce stress sensitivity may help to decrease symptoms of psychopathology in adolescent boys.

  View details for DOI 10.1016/j.biopsych.2024.01.011

  View details for PubMedID 38272286

• Neuroanatomical dimensions in medication-free individuals with major depressive disorder and treatment response to SSRI antidepressant medications or placebo. Nature. Mental health Fu, C. H., Antoniades, M., Erus, G., Garcia, J. A., Fan, Y., Arnone, D., Arnott, S. R., Chen, T., Choi, K. S., Fatt, C. C., Frey, B. N., Frokjaer, V. G., Ganz, M., Godlewska, B. R., Hassel, S., Ho, K., McIntosh, A. M., Qin, K., Rotzinger, S., Sacchet, M. D., Savitz, J., Shou, H., Singh, A., Stolicyn, A., Strigo, I., Strother, S. C., Tosun, D., Victor, T. A., Wei, D., Wise, T., Zahn, R., Anderson, I. M., Craighead, W. E., Deakin, J. F., Dunlop, B. W., Elliott, R., Gong, Q., Gotlib, I. H., Harmer, C. J., Kennedy, S. H., Knudsen, G. M., Mayberg, H. S., Paulus, M. P., Qiu, J., Trivedi, M. H., Whalley, H. C., Yan, C. G., Young, A. H., Davatzikos, C. 2024; 2 (2): 164-176

  Abstract

  Major depressive disorder (MDD) is a heterogeneous clinical syndrome with widespread subtle neuroanatomical correlates. Our objective was to identify the neuroanatomical dimensions that characterize MDD and predict treatment response to selective serotonin reuptake inhibitor (SSRI) antidepressants or placebo. In the COORDINATE-MDD consortium, raw MRI data were shared from international samples (N = 1,384) of medication-free individuals with first-episode and recurrent MDD (N = 685) in a current depressive episode of at least moderate severity, but not treatment-resistant depression, as well as healthy controls (N = 699). Prospective longitudinal data on treatment response were available for a subset of MDD individuals (N = 359). Treatments were either SSRI antidepressant medication (escitalopram, citalopram, sertraline) or placebo. Multi-center MRI data were harmonized, and HYDRA, a semi-supervised machine-learning clustering algorithm, was utilized to identify patterns in regional brain volumes that are associated with disease. MDD was optimally characterized by two neuroanatomical dimensions that exhibited distinct treatment responses to placebo and SSRI antidepressant medications. Dimension 1 was characterized by preserved gray and white matter (N = 290 MDD), whereas Dimension 2 was characterized by widespread subtle reductions in gray and white matter (N = 395 MDD) relative to healthy controls. Although there were no significant differences in age of onset, years of illness, number of episodes, or duration of current episode between dimensions, there was a significant interaction effect between dimensions and treatment response. Dimension 1 showed a significant improvement in depressive symptoms following treatment with SSRI medication (51.1%) but limited changes following placebo (28.6%). By contrast, Dimension 2 showed comparable improvements to either SSRI (46.9%) or placebo (42.2%) (β = -18.3, 95% CI (-34.3 to -2.3), P = 0.03). Findings from this case-control study indicate that neuroimaging-based markers can help identify the disease-based dimensions that constitute MDD and predict treatment response.

  View details for DOI 10.1038/s44220-023-00187-w

  View details for PubMedID 38948238

  View details for PubMedCentralID PMC11211072

• Multi-site benchmark classification of major depressive disorder using machine learning on cortical and subcortical measures. Scientific reports Belov, V., Erwin-Grabner, T., Aghajani, M., Aleman, A., Amod, A. R., Basgoze, Z., Benedetti, F., Besteher, B., Bülow, R., Ching, C. R., Connolly, C. G., Cullen, K., Davey, C. G., Dima, D., Dols, A., Evans, J. W., Fu, C. H., Gonul, A. S., Gotlib, I. H., Grabe, H. J., Groenewold, N., Hamilton, J. P., Harrison, B. J., Ho, T. C., Mwangi, B., Jaworska, N., Jahanshad, N., Klimes-Dougan, B., Koopowitz, S. M., Lancaster, T., Li, M., Linden, D. E., MacMaster, F. P., Mehler, D. M., Melloni, E., Mueller, B. A., Ojha, A., Oudega, M. L., Penninx, B. W., Poletti, S., Pomarol-Clotet, E., Portella, M. J., Pozzi, E., Reneman, L., Sacchet, M. D., Sämann, P. G., Schrantee, A., Sim, K., Soares, J. C., Stein, D. J., Thomopoulos, S. I., Uyar-Demir, A., van der Wee, N. J., van der Werff, S. J., Völzke, H., Whittle, S., Wittfeld, K., Wright, M. J., Wu, M. J., Yang, T. T., Zarate, C., Veltman, D. J., Schmaal, L., Thompson, P. M., Goya-Maldonado, R. 2024; 14 (1): 1084

  Abstract

  Machine learning (ML) techniques have gained popularity in the neuroimaging field due to their potential for classifying neuropsychiatric disorders. However, the diagnostic predictive power of the existing algorithms has been limited by small sample sizes, lack of representativeness, data leakage, and/or overfitting. Here, we overcome these limitations with the largest multi-site sample size to date (N = 5365) to provide a generalizable ML classification benchmark of major depressive disorder (MDD) using shallow linear and non-linear models. Leveraging brain measures from standardized ENIGMA analysis pipelines in FreeSurfer, we were able to classify MDD versus healthy controls (HC) with a balanced accuracy of around 62%. But after harmonizing the data, e.g., using ComBat, the balanced accuracy dropped to approximately 52%. Accuracy results close to random chance levels were also observed in stratified groups according to age of onset, antidepressant use, number of episodes and sex. Future studies incorporating higher dimensional brain imaging/phenotype features, and/or using more advanced machine and deep learning methods may yield more encouraging prospects.

  View details for DOI 10.1038/s41598-023-47934-8

  View details for PubMedID 38212349

  View details for PubMedCentralID PMC10784593

• A network analysis of psychopathology in young Black children: Implications for predicting outcomes in adolescence. Journal of affective disorders Hyat, M., Miller, J. G., Gotlib, I. H. 2024

  Abstract

  Network analysis may identify specific symptoms involved in the maintenance and development of psychopathology. This approach, however, has not been applied to the study of young Black children, a population facing unique challenges and developmental risks. It is also unclear whether network analysis identifies early symptoms in Black children that are linked to their longer-term difficulties and strengths in adolescence.We conducted a network analysis of emotional and behavioral difficulties in 1238 Black (non-Hispanic) children from the age-3 assessment in the Future of Families and Child Wellbeing Study (47 % female). We also explored whether early childhood symptoms predict subsequent caregiver-reported internalizing and externalizing problems, and youth-reported social competencies and extracurricular and community involvement, at the age-15 assessment.We identified specific symptoms of externalizing and emotional reactivity as central in the network. Symptoms of emotional reactivity were also involved in comorbidity, bridging different communities of symptoms. Using elastic net models, we identified specific central and bridge symptoms, but also peripheral network symptoms, that contributed uniquely to the prediction of internalizing and externalizing problems in adolescence. Early childhood symptoms were less predictive of positive outcomes in adolescence.This study identified central and bridge symptoms in young Black children, an underrepresented population in network analysis research. Some of these central and bridge symptoms, but also peripheral network symptoms, may be useful targets in early interventions to prevent long-term difficulties. Conversely, network approaches to understanding early psychopathology may have less utility for predicting Black children's subsequent strengths in adolescence.

  View details for DOI 10.1016/j.jad.2024.01.071

  View details for PubMedID 38211758

• Neighborhood Socioeconomic Disadvantage and White Matter Microstructure of the Arcuate Fasciculus and Uncinate Fasciculus in Adolescents. Biological psychiatry global open science Kulla, A., Coury, S., Garcia, J. M., Teresi, G. I., Sisk, L. M., Hansen, M., Miller, J. G., Gotlib, I. H., Ho, T. C. 2024; 4 (1): 61-72

  Abstract

  Neighborhood- or area-level socioeconomic disadvantage is associated with neural alterations across the life span. However, few studies have examined the effects of neighborhood disadvantage on white matter microstructure during adolescence, an important period of development that coincides with increased risk for psychopathology.In 200 adolescents (ages 13-20 years; 54.5% female, 4% nonbinary) recruited from 2 studies enriched for early adversity and depression, we examined whether neighborhood socioeconomic disadvantage derived from census tract data was related to white matter microstructure in several major white matter tracts. We also examined whether depressive symptoms and sex moderated these associations.Greater neighborhood socioeconomic disadvantage was associated with lower fractional anisotropy (FA) in the left arcuate fasciculus (β = -0.24, false discovery rate [FDR]-corrected p = .035) and right uncinate fasciculus (β = -0.32, FDR-corrected p = .002) above and beyond the effects of family-level socioeconomic status. Depressive symptoms significantly moderated the association between left arcuate fasciculus FA and both neighborhood (β = 0.17, FDR-corrected p = .026) and unemployment (β = 0.22, FDR-corrected p = .004) disadvantage such that these associations were only significant in adolescents who reported less severe depression. Sex did not moderate the association between socioeconomic disadvantage and FA in these tracts.Greater neighborhood socioeconomic disadvantage, particularly poverty and educational attainment levels, was associated with lower FA in the arcuate fasciculus and uncinate fasciculus above and beyond the effects of family-level measures of socioeconomic status. These patterns were only observed in adolescents with low levels of depression, suggesting that we must be cautious about generalizing these findings to youths who struggle with mental health difficulties.

  View details for DOI 10.1016/j.bpsgos.2023.10.002

  View details for PubMedID 38076598

  View details for PubMedCentralID PMC10709004

• Associations among early life adversity, sleep disturbances, and depressive symptoms in adolescent females and males: a longitudinal investigation. Journal of child psychology and psychiatry, and allied disciplines Uy, J. P., Gotlib, I. H. 2023

  Abstract

  BACKGROUND: Exposure to adversity early in life (ELA) has been associated with elevated risk for depression during adolescence, particularly for females; the mechanisms underlying this association, however, are poorly understood. One potential mechanism linking ELA and sex differences in depressive symptoms is sleep disturbances, which increase during adolescence and are more common in females. Here, we examined whether sleep disturbances mediate the association between ELA and increases in depressive symptoms during adolescence and whether this mediation differs by sex.METHODS: 224 (N=132 females) youth were recruited at age 9-13years and assessed every 2years across three timepoints. At the first timepoint, we conducted extensive interviews about stressful events participants experienced; participants provided subjective severity ratings of events and we objectively scored the severity of each event. Self-reported sleep disturbances and depressive symptoms were assessed at all timepoints. We conducted linear mixed models to estimate both initial levels and changes in sleep disturbances and depressive symptoms, and moderated mediation analyses to test whether initial levels and/or changes in sleep disturbances mediated the association of ELA (objective and subjective) with increases in depressive symptoms across adolescence and whether the mediations differed by sex.RESULTS: While higher initial levels and increases in sleep problems were uniquely associated with increases in depressive symptoms for males and females, they were related to ELA differently by sex. For females, greater ELA (both objectively and subjectively rated) was associated with higher initial levels of sleep problems, which in turn were associated with increases in depressive symptoms from early to late adolescence. In contrast, for males, ELA exposure was not associated with either initial levels of, or increases in, sleep problems.CONCLUSIONS: These findings highlight the role of sleep disturbances during the transition to adolescence in mediating sex differences in the effects of ELA on depressive symptoms.

  View details for DOI 10.1111/jcpp.13942

  View details for PubMedID 38156675

• Exploring sex differences in trajectories of pubertal development and mental health following early adversity. Psychoneuroendocrinology Ho, T. C., Buthmann, J., Chahal, R., Miller, J. G., Gotlib, I. H. 2023; 161: 106944

  Abstract

  Despite evidence that early life adversity (ELA) affects mental health in adolescence, we know little about sex differences in how distinct dimensions of adversity affect development and their corresponding effects on mental health. In this three-wave longitudinal study, 209 participants (118 females; ages 9-13 years at baseline) provided objective (salivary hormones, BMI, age of menarche) and subjective (perceived gonadal and adrenal status) measures of puberty and physical development, and reported on levels of internalizing and externalizing symptoms at all timepoints. Participants also reported lifetime exposure to three distinct types of ELA: deprivation, threat, and unpredictability. Using generalized additive mixed models, we tested within each sex whether dimensions of adversity were associated with longitudinal changes in measures of pubertal and physical development, and whether these indices of development were associated with trajectories of internalizing and externalizing symptoms. In females, experiences of threat and unpredictability were significantly associated with earlier pubertal timing (e.g., age of menarche) whereas experiences of deprivation were associated with steeper increases in BMI; further, faster pubertal tempo (i.e., steeper increases in pubertal stage) was associated with increases in internalizing and externalizing symptoms. In males, however, ELA was not associated with any measures of pubertal or physical development or with symptoms. Together, our results suggest that adverse experiences during early life have sex-selective consequences for pubertal and physical maturation and mental health trajectories in ways that may elucidate why females are at higher risk for mental health difficulties during puberty, particularly following exposure to unpredictable and threatening experiences of adversity.

  View details for DOI 10.1016/j.psyneuen.2023.106944

  View details for PubMedID 38171040

• A cognitive model of depression and political attitudes ELECTORAL STUDIES Bernardi, L., Sala, G., Gotlib, I. H. 2024; 87

  View details for DOI 10.1016/j.electstud.2023.102737

  View details for Web of Science ID 001165959700001

• Early life stress predicts trajectories of emotional problems and hippocampal volume in adolescence. European child & adolescent psychiatry Buthmann, J. L., Miller, J. G., Uy, J. P., Coury, S. M., Jo, B., Gotlib, I. H. 2023

  Abstract

  Exposure to early life stress (ELS) has been consistently associated with adverse emotional and neural consequences in youth. The development of brain structures such as the hippocampus, which plays a significant role in stress and emotion regulation, may be particularly salient in the development of psychopathology. Prior work has documented smaller hippocampal volume (HCV) in relation to both ELS exposure and risk for psychopathology. We used longitudinal k-means clustering to identify simultaneous trajectories of HCV and emotional problems in 155 youth across three assessments conducted approximately two years apart (mean baseline age = 11.33 years, 57% female). We also examined depressive symptoms and resilience approximately two years after the third timepoint. We identified three clusters of participants: a cluster with high HCV and low emotional problems; a cluster with low HCV and high emotional problems; and a cluster with low HCV and low emotional problems. Importantly, severity of ELS was associated with greater likelihood of belonging to the low HCV/high symptom cluster than to the low HCV/low symptom cluster. Further, low HCV/high symptom participants had more depressive symptoms and lower resilience scores than did participants in the low HCV/low symptom, but not than in the high HCV/low symptom cluster. Our findings suggest that smaller HCV indexes biological sensitivity to stress. This adds to our understanding of the ways in which ELS can affect hippocampal and emotional development in young people and points to hippocampal volume as a marker of susceptibility to context.

  View details for DOI 10.1007/s00787-023-02331-4

  View details for PubMedID 38135803

  View details for PubMedCentralID 6179355

• Genetics, epigenetics, and neurobiology of childhood-onset depression: an umbrella review. Molecular psychiatry Singh, M. K., Gorelik, A. J., Stave, C., Gotlib, I. H. 2023

  Abstract

  Depression is a serious and persistent psychiatric disorder that commonly first manifests during childhood. Depression that starts in childhood is increasing in frequency, likely due both to evolutionary trends and to increased recognition of the disorder. In this umbrella review, we systematically searched the extant literature for genetic, epigenetic, and neurobiological factors that contribute to a childhood onset of depression. We searched PubMed, EMBASE, OVID/PsychInfo, and Google Scholar with the following inclusion criteria: (1) systematic review or meta-analysis from a peer-reviewed journal; (2) inclusion of a measure assessing early age of onset of depression; and (3) assessment of neurobiological, genetic, environmental, and epigenetic predictors of early onset depression. Findings from 89 systematic reviews of moderate to high quality suggest that childhood-onset depressive disorders have neurobiological, genetic, environmental, and epigenetic roots consistent with a diathesis-stress theory of depression. This review identified key putative markers that may be targeted for personalized clinical decision-making and provide important insights concerning candidate mechanisms that might underpin the early onset of depression.

  View details for DOI 10.1038/s41380-023-02347-x

  View details for PubMedID 38102485

  View details for PubMedCentralID 5522740

• Biological sensitivity to adolescent-parent discrepancies in perceived parental warmth. Comprehensive psychoneuroendocrinology Buthmann, J. L., LeMoult, J., Miller, J. G., Berens, A., Gotlib, I. H. 2023; 16: 100211

  Abstract

  Parenting behaviors are formative to the psychological development of young people; however, parent and adolescent perceptions of parenting are only moderately correlated with each other. Whereas discrepant perceptions may represent a normative process of deindividuation from caregivers in some adolescents, in others a discrepancy might predict psychological maladjustment. The biological sensitivity to context model provides a framework from which individual differences in development can be estimated in adolescents whose perceptions of parenting diverge from those of their parents.At baseline we obtained diurnal cortisol samples from US adolescents (M = 13.37 years of age, SD = 1.06) as well as parents' and adolescents' ratings of parental warmth; we obtained adolescent-reported symptoms of psychopathology at baseline and again at follow-up two years later (N = 108, 57.5% female). We estimated waking cortisol, cortisol awakening response, and daytime cortisol slopes using piecewise regression models.Lower adolescent than parent ratings of parental warmth predicted increased externalizing symptoms at follow-up. Higher waking cortisol and steeper cortisol awakening response and daytime slopes predicted increased internalizing symptoms at follow-up. Further, discrepant ratings of parental warmth interacted with cortisol awakening response and daytime slopes such that greater discrepancies predicted greater increases in externalizing symptoms in adolescents with steeper cortisol slopes.These findings indicate that steeper changes in cortisol production throughout the day index a greater sensitivity to perceived parental warmth. Lower adolescent than parent ratings of parental warmth may represent dysfunction in the parental relationship rather than a normative process of deindividuation in adolescents with steeper diurnal cortisol slopes.

  View details for DOI 10.1016/j.cpnec.2023.100211

  View details for PubMedID 37808874

  View details for PubMedCentralID PMC10550797

• Preparation and processing of dried blood spots for microRNA sequencing. Biology methods & protocols Morgunova, A., Ibrahim, P., Chen, G. G., Coury, S. M., Turecki, G., Meaney, M. J., Gifuni, A., Gotlib, I. H., Nagy, C., Ho, T. C., Flores, C. 2023; 8 (1): bpad020

  Abstract

  Dried blood spots (DBS) are biological samples commonly collected from newborns and in geographic areas distanced from laboratory settings for the purposes of disease testing and identification. MicroRNAs (miRNAs)-small non-coding RNAs that regulate gene activity at the post-transcriptional level-are emerging as critical markers and mediators of disease, including cancer, infectious diseases, and mental disorders. This protocol describes optimized procedural steps for utilizing DBS as a reliable source of biological material for obtaining peripheral miRNA expression profiles. We outline key practices, such as the method of DBS rehydration that maximizes RNA extraction yield, and the use of degenerate oligonucleotide adapters to mitigate ligase-dependent biases that are associated with small RNA sequencing. The standardization of miRNA readout from DBS offers numerous benefits: cost-effectiveness in sample collection and processing, enhanced reliability and consistency of miRNA profiling, and minimal invasiveness that facilitates repeated testing and retention of participants. The use of DBS-based miRNA sequencing is a promising method to investigate disease mechanisms and to advance personalized medicine.

  View details for DOI 10.1093/biomethods/bpad020

  View details for PubMedID 37901452

  View details for PubMedCentralID PMC10603595

• Early life stress, sleep disturbances, and depressive symptoms during adolescence: The role of the cingulum bundle. Developmental cognitive neuroscience Uy, J. P., Ho, T. C., Buthmann, J. L., Coury, S. M., Gotlib, I. H. 2023; 63: 101303

  Abstract

  Adolescence is often characterized by sleep disturbances that can affect the development of white matter tracts implicated in affective and cognitive regulation, including the cingulate portion of the cingulum bundle (CGC) and the uncinate fasciculus (UF). These effects may be exacerbated in adolescents exposed to early life adversity (ELA). We examined the longitudinal relations between sleep problems and CGC and UF microstructure during adolescence and their relation to depressive symptoms as a function of exposure to ELA. We assessed self-reported sleep disturbances and depressive symptoms and acquired diffusion-weighted MRI scans twice: in early adolescence (9-13 years) and four years later (13-17 years) (N=72 complete cases). Independent of ELA, higher initial levels and increases in sleep problems were related to increases in depressive symptoms. Further, increases in right CGC fractional anisotropy (FA) mediated the association between sleep problems and depressive symptoms for youth who experienced lower, but not higher, levels of ELA. In youth with higher ELA, higher initial levels of and steeper decreases in sleep problems were associated with greater decreases in right UF FA, but were unrelated to depressive symptoms. Our findings highlight the importance of sleep quality in shaping fronto-cingulate-limbic tract development and depressive symptoms during adolescence.

  View details for DOI 10.1016/j.dcn.2023.101303

  View details for PubMedID 37738837

• Early life stress moderates the relation between systemic inflammation and neural activation to reward in adolescents both cross-sectionally and longitudinally NEUROPSYCHOPHARMACOLOGY Yuan, J. P., Coury, S. M., Ho, T. C., Gotlib, I. H. 2023

  View details for DOI 10.1038/s41386-023-01708

  View details for Web of Science ID 001059620400002

• Early life stress moderates the relation between systemic inflammation and neural activation to reward in adolescents both cross-sectionally and longitudinally. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology Yuan, J. P., Coury, S. M., Ho, T. C., Gotlib, I. H. 2023

  Abstract

  Elevated levels of systemic inflammation are associated with altered reward-related brain function in ventral striatal areas of the brain like the nucleus accumbens (NAcc). In adolescents, cross-sectional research indicates that exposure to early life stress (ELS) can moderate the relation between inflammation and neural activation, which may contribute to atypical reward function; however, no studies have tested whether this moderation by ELS of neuroimmune associations persists over time. Here, we conducted a cross-sectional analysis and the first exploratory longitudinal analysis testing whether cumulative severity of ELS moderates the association of systemic inflammation with reward-related processing in the NAcc in adolescents (n = 104; 58F/46M; M[SD] age = 16.00[1.45] years; range = 13.07-19.86 years). For the cross-sectional analysis, we modeled a statistical interaction between ELS and levels of C-reactive protein (CRP) predicting NAcc activation during the anticipation and outcome phases of a monetary reward task. We found that higher CRP was associated with blunted NAcc activation during the outcome of reward in youth who experienced higher levels of ELS (β = -0.31; p = 0.006). For the longitudinal analysis, we modeled an interaction between ELS and change in CRP predicting change in NAcc activation across 2 years. This analysis similarly showed that increasing CRP over time was associated with decreasing NAcc during reward outcomes in youth who experienced higher levels of ELS (β = -0.47; p = 0.022). Both findings support contemporary theoretical frameworks involving associations among inflammation, reward-related brain function, and ELS exposure, and suggest that experiencing ELS can have significant and enduring effects on neuroimmune function and adolescent neurodevelopment.

  View details for DOI 10.1038/s41386-023-01708-y

  View details for PubMedID 37673968

  View details for PubMedCentralID 7147972

• Teaching or learning from baby: Inducing explicit parenting goals influences caregiver intrusiveness. Developmental psychology King, L. S., Hill, K. E., Rangel, E., Gotlib, I. H., Humphreys, K. L. 2023

  Abstract

  Caregivers' goals influence their interactions with their children. In this preregistered study, we examined whether directing parents to teach their baby versus learn from their baby influenced the extent to which they engaged in intrusive (e.g., controlling, adult-centered rather than child-centered), sensitive, warm, or cognitively stimulating caregiving behaviors. Mothers and their 6-month-old infants (N = 66; 32 female infants) from the San Francisco Bay Area participated in a 10-min "free-play" interaction, coded in 2-min epochs for degree of parental intrusiveness. Prior to the final epoch, mothers were randomly assigned to receive instructions to focus on (a) teaching something to their infant or (b) learning something from their infant. A control group of mothers received no instructions. Analyses of within-person changes in intrusive behavior from before to after receiving these instructions indicated that mothers assigned to teach their infant increased in intrusiveness whereas mothers assigned to learn from their infant and mothers in the control group did not significantly change in intrusiveness. The study provides experimental evidence that caregivers' explicit goals to teach infants result, on average, in more controlling and adult-centered caregiving behavior. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

  View details for DOI 10.1037/dev0001592

  View details for PubMedID 37616120

• Depressive rumination and political engagement JOURNAL OF ELECTIONS PUBLIC OPINION AND PARTIES Bernardi, L., Gotlib, I. H., Bernardi, F. 2023

  View details for DOI 10.1080/17457289.2023.2246371

  View details for Web of Science ID 001047963100001

• Meta-Analysis of Functional Neuroimaging in Adults With Major Depressive Disorder Klassen, A. M., Baten, C., Shepherd, J. H., Zamora, G., Saravia, S., Pritchard, E., Ali, Z., Jordan, J., Kahlon, S. K., Maly, G., Duran, M., Santos, S. L., Kaur, A., Saini, A., Nimarko, A. F., Hedges, D. W., Hamilton, J., Gotlib, I. H., Sacchet, M. D., Miller, C. H. ELSEVIER SCIENCE INC. 2023: S207

  View details for Web of Science ID 000993018500501

• Early Life Stress Predicts Adolescent Trajectories of Emotional Problems and Hippocampal Volume Buthmann, J., Jonas, M. G., Coury, S., Uy, J., Gotlib, I. ELSEVIER SCIENCE INC. 2023: S86

  View details for Web of Science ID 000993018500205

• Effects of Developmental Age and Length of Illness in Major Depressive Disorder: A Meta-Analysis of Functional Magnetic Resonance Imaging Studies Baten, C., Klassen, A. M., Shepherd, J. H., Zamora, G., Pritchard, E., Saravia, S., Ali, Z., Jordan, J., Kahlon, S. K., Maly, G., Duran, M., Santos, S. L., Kaur, A., Saini, A., Nimarko, A. F., Hedges, D. W., Hamilton, P., Gotlib, I. H., Sacchet, M. D., Miller, C. H. ELSEVIER SCIENCE INC. 2023: S239

  View details for Web of Science ID 000993018500578

• A Meta-Analysis of Functional Neuroimaging Studies of Major Depressive Disorder in Youth Zamora, G., Baten, C., Klassen, A. M., Shepherd, J. H., Pritchard, E., Saravia, S., Ali, Z., Jordan, J., Kahlon, S. K., Maly, G., Duran, M., Santos, S., Kaur, A., Saini, A., Nimarko, A. F., Hedges, D. W., Hamilton, P., Gotlib, I. H., Sacchet, M. D., Miller, C. H. ELSEVIER SCIENCE INC. 2023: S280

  View details for Web of Science ID 000993018500678

• Concurrent validity and reliability of suicide risk assessment instruments: A meta-analysis of 20 instruments across 27 international cohorts. Neuropsychology Campos, A. I., Van Velzen, L. S., Veltman, D. J., Pozzi, E., Ambrogi, S., Ballard, E. D., Banaj, N., Başgöze, Z., Bellow, S., Benedetti, F., Bollettini, I., Brosch, K., Canales-Rodríguez, E. J., Clarke-Rubright, E. K., Colic, L., Connolly, C. G., Courtet, P., Cullen, K. R., Dannlowski, U., Dauvermann, M. R., Davey, C. G., Deverdun, J., Dohm, K., Erwin-Grabner, T., Goya-Maldonado, R., Fani, N., Fortea, L., Fuentes-Claramonte, P., Gonul, A. S., Gotlib, I. H., Grotegerd, D., Harris, M. A., Harrison, B. J., Haswell, C. C., Hawkins, E. L., Hill, D., Hirano, Y., Ho, T. C., Jollant, F., Jovanovic, T., Kircher, T., Klimes-Dougan, B., le Bars, E., Lochner, C., McIntosh, A. M., Meinert, S., Mekawi, Y., Melloni, E., Mitchell, P., Morey, R. A., Nakagawa, A., Nenadić, I., Olié, E., Pereira, F., Phillips, R. D., Piras, F., Poletti, S., Pomarol-Clotet, E., Radua, J., Ressler, K. J., Roberts, G., Rodriguez-Cano, E., Sacchet, M. D., Salvador, R., Sandu, A. L., Shimizu, E., Singh, A., Spalletta, G., Steele, J. D., Stein, D. J., Stein, F., Stevens, J. S., Teresi, G. I., Uyar-Demir, A., van der Wee, N. J., van der Werff, S. J., van Rooij, S. J., Vecchio, D., Verdolini, N., Vieta, E., Waiter, G. D., Whalley, H., Whittle, S. L., Yang, T. T., Zarate, C. A., Thompson, P. M., Jahanshad, N., van Harmelen, A. L., Blumberg, H. P., Schmaal, L., Rentería, M. E. 2023; 37 (3): 315-329

  Abstract

  A major limitation of current suicide research is the lack of power to identify robust correlates of suicidal thoughts or behavior. Variation in suicide risk assessment instruments used across cohorts may represent a limitation to pooling data in international consortia.Here, we examine this issue through two approaches: (a) an extensive literature search on the reliability and concurrent validity of the most commonly used instruments and (b) by pooling data (N ∼ 6,000 participants) from cohorts from the Enhancing NeuroImaging Genetics Through Meta-Analysis (ENIGMA) Major Depressive Disorder and ENIGMA-Suicidal Thoughts and Behaviour working groups, to assess the concurrent validity of instruments currently used for assessing suicidal thoughts or behavior.We observed moderate-to-high correlations between measures, consistent with the wide range (κ range: 0.15-0.97; r range: 0.21-0.94) reported in the literature. Two common multi-item instruments, the Columbia Suicide Severity Rating Scale and the Beck Scale for Suicidal Ideation were highly correlated with each other (r = 0.83). Sensitivity analyses identified sources of heterogeneity such as the time frame of the instrument and whether it relies on self-report or a clinical interview. Finally, construct-specific analyses suggest that suicide ideation items from common psychiatric questionnaires are most concordant with the suicide ideation construct of multi-item instruments.Our findings suggest that multi-item instruments provide valuable information on different aspects of suicidal thoughts or behavior but share a modest core factor with single suicidal ideation items. Retrospective, multisite collaborations including distinct instruments should be feasible provided they harmonize across instruments or focus on specific constructs of suicidality. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

  View details for DOI 10.1037/neu0000850

  View details for PubMedID 37011159

• The default mode network is associated with changes in internalizing and externalizing problems differently in adolescent boys and girls. Development and psychopathology Lee, Y., Chahal, R., Gotlib, I. H. 2023: 1-10

  Abstract

  Internalizing and externalizing problems that emerge during adolescence differentially increase boys' and girls' risk for developing psychiatric disorders. It is not clear, however, whether there are sex differences in the intrinsic functional architecture of the brain that underlie changes in the severity of internalizing and externalizing problems in adolescents. Using resting-state fMRI data and self-reports of behavioral problems obtained from 128 adolescents (73 females; 9-14 years old) at two timepoints, we conducted multivoxel pattern analysis to identify resting-state functional connectivity markers at baseline that predict changes in the severity of internalizing and externalizing problems in boys and girls 2 years later. We found sex-differentiated involvement of the default mode network in changes in internalizing and externalizing problems. Whereas changes in internalizing problems were associated with the dorsal medial subsystem in boys and with the medial temporal subsystem in girls, changes in externalizing problems were predicted by hyperconnectivity between core nodes of the DMN and frontoparietal network in boys and hypoconnectivity between the DMN and affective networks in girls. Our results suggest that different neural mechanisms predict changes in internalizing and externalizing problems in adolescent boys and girls and offer insights concerning mechanisms that underlie sex differences in the expression of psychopathology in adolescence.

  View details for DOI 10.1017/S0954579423000111

  View details for PubMedID 36847268

• Functional connectivity signatures of major depressive disorder: machine learning analysis of two multicenter neuroimaging studies. Molecular psychiatry Gallo, S., El-Gazzar, A., Zhutovsky, P., Thomas, R. M., Javaheripour, N., Li, M., Bartova, L., Bathula, D., Dannlowski, U., Davey, C., Frodl, T., Gotlib, I., Grimm, S., Grotegerd, D., Hahn, T., Hamilton, P. J., Harrison, B. J., Jansen, A., Kircher, T., Meyer, B., Nenadić, I., Olbrich, S., Paul, E., Pezawas, L., Sacchet, M. D., Sämann, P., Wagner, G., Walter, H., Walter, M., van Wingen, G. 2023

  Abstract

  The promise of machine learning has fueled the hope for developing diagnostic tools for psychiatry. Initial studies showed high accuracy for the identification of major depressive disorder (MDD) with resting-state connectivity, but progress has been hampered by the absence of large datasets. Here we used regular machine learning and advanced deep learning algorithms to differentiate patients with MDD from healthy controls and identify neurophysiological signatures of depression in two of the largest resting-state datasets for MDD. We obtained resting-state functional magnetic resonance imaging data from the REST-meta-MDD (N = 2338) and PsyMRI (N = 1039) consortia. Classification of functional connectivity matrices was done using support vector machines (SVM) and graph convolutional neural networks (GCN), and performance was evaluated using 5-fold cross-validation. Features were visualized using GCN-Explainer, an ablation study and univariate t-testing. The results showed a mean classification accuracy of 61% for MDD versus controls. Mean accuracy for classifying (non-)medicated subgroups was 62%. Sex classification accuracy was substantially better across datasets (73-81%). Visualization of the results showed that classifications were driven by stronger thalamic connections in both datasets, while nearly all other connections were weaker with small univariate effect sizes. These results suggest that whole brain resting-state connectivity is a reliable though poor biomarker for MDD, presumably due to disease heterogeneity as further supported by the higher accuracy for sex classification using the same methods. Deep learning revealed thalamic hyperconnectivity as a prominent neurophysiological signature of depression in both multicenter studies, which may guide the development of biomarkers in future studies.

  View details for DOI 10.1038/s41380-023-01977-5

  View details for PubMedID 36792654

  View details for PubMedCentralID 4814515

• AI-based dimensional neuroimaging system for characterizing heterogeneity in brain structure and function in major depressive disorder: COORDINATE-MDD consortium design and rationale. BMC psychiatry Fu, C. H., Erus, G., Fan, Y., Antoniades, M., Arnone, D., Arnott, S. R., Chen, T., Choi, K. S., Fatt, C. C., Frey, B. N., Frokjaer, V. G., Ganz, M., Garcia, J., Godlewska, B. R., Hassel, S., Ho, K., McIntosh, A. M., Qin, K., Rotzinger, S., Sacchet, M. D., Savitz, J., Shou, H., Singh, A., Stolicyn, A., Strigo, I., Strother, S. C., Tosun, D., Victor, T. A., Wei, D., Wise, T., Woodham, R. D., Zahn, R., Anderson, I. M., Deakin, J. F., Dunlop, B. W., Elliott, R., Gong, Q., Gotlib, I. H., Harmer, C. J., Kennedy, S. H., Knudsen, G. M., Mayberg, H. S., Paulus, M. P., Qiu, J., Trivedi, M. H., Whalley, H. C., Yan, C., Young, A. H., Davatzikos, C. 2023; 23 (1): 59

  Abstract

  BACKGROUND: Efforts to develop neuroimaging-based biomarkers in major depressive disorder (MDD), at the individual level, have been limited to date. As diagnostic criteria are currently symptom-based, MDD is conceptualized as a disorder rather than a disease with a known etiology; further, neural measures are often confounded by medication status and heterogeneous symptom states.METHODS: We describe a consortium to quantify neuroanatomical and neurofunctional heterogeneity via the dimensions of novel multivariate coordinate system (COORDINATE-MDD). Utilizing imaging harmonization and machine learning methods in a large cohort of medication-free, deeply phenotyped MDD participants, patterns of brain alteration are defined in replicable and neurobiologically-based dimensions and offer the potential to predict treatment response at the individual level. International datasets are being shared from multi-ethnic community populations, first episode and recurrent MDD, which are medication-free, in a current depressive episode with prospective longitudinal treatment outcomes and in remission. Neuroimaging data consist of de-identified, individual, structural MRI and resting-state functional MRI with additional positron emission tomography (PET) data at specific sites. State-of-the-art analytic methods include automated image processing for extraction of anatomical and functional imaging variables, statistical harmonization of imaging variables to account for site and scanner variations, and semi-supervised machine learning methods that identify dominant patterns associated with MDD from neural structure and function in healthy participants.RESULTS: We are applying an iterative process by defining the neural dimensions that characterise deeply phenotyped samples and then testing the dimensions in novel samples to assess specificity and reliability. Crucially, we aim to use machine learning methods to identify novel predictors of treatment response based on prospective longitudinal treatment outcome data, and we can externally validate the dimensions in fully independent sites.CONCLUSION: We describe the consortium, imaging protocols and analytics using preliminary results. Our findings thus far demonstrate how datasets across many sites can be harmonized and constructively pooled to enable execution of this large-scale project.

  View details for DOI 10.1186/s12888-022-04509-7

  View details for PubMedID 36690972

• Shorter maternal leukocyte telomere length following cesarean birth: Implications for future research Panelli, D. M., Mayo, J. A., Wong, R. J., Becker, M., Maric, I., Wu, E., Gotlib, I. H., Aghaeepour, N., Druzin, M. L., Stevenson, D. K., Shaw, G. M., Bianco, K. MOSBY-ELSEVIER. 2023: S456-S457

  View details for Web of Science ID 000909337401260

• The Functioning of Offspring of Depressed Parents: Current Status, Unresolved Issues, and Future Directions ANNUAL REVIEW OF DEVELOPMENTAL PSYCHOLOGY Gotlib, I. H., Buthmann, J. L., Miller, J. G. 2023; 5: 375-397

  View details for DOI 10.1146/annurev-devpsych-120221-033623

  View details for Web of Science ID 001315423300018

• Prefrontal activation in preschool children is associated with maternal adversity and child temperament: A preliminary fNIRS study of inhibitory control DEVELOPMENTAL PSYCHOBIOLOGY Miller, J. G., Hyat, M., Perlman, S. B., Wong, R. J., Shaw, G. M., Stevenson, D. K., Gotlib, I. H. 2023; 65 (1): e22351

  Abstract

  Exposure to adversity is a well-documented risk factor for cognitive, behavioral, and mental health problems. In fact, the consequences of adversity may be intergenerational. A growing body of research suggests that maternal exposures to adversity, including those prior to childbirth, are associated with offspring biobehavioral development. In a sample of 36 mothers and their preschool-age children (mean child age = 4.21 ± 0.92 years), we used functional near-infrared spectroscopy to replicate and extend this work to include brain activation during inhibitory control in young children. We found that measures of maternal exposure to adversity, including cumulative, childhood, and preconception exposures, were significantly and positively associated with activation in the right frontopolar prefrontal cortex (PFC) and in the left temporal and parietal clusters during inhibitory control. In addition, and consistent with previous findings, children's increased negative affect and decreased effortful control were associated with increased right PFC activation during inhibitory control. These findings provide preliminary evidence that maternal and dispositional risk factors are linked to alterations in PFC functioning during the preschool years. Children of mothers with a history of exposure to adversity, as well as children who are less temperamentally regulated, may require increased neural resources to meet the cognitive demands of inhibitory control.

  View details for DOI 10.1002/dev.22351

  View details for Web of Science ID 000895767900001

  View details for PubMedID 36567657

• Objective and subjective sleep health in adolescence: Associations with puberty and affect. Journal of sleep research Kirshenbaum, J. S., Coury, S. M., Colich, N. L., Manber, R., Gotlib, I. H. 2022: e13805

  Abstract

  Sleep health tends to worsen during adolescence, partially due to pubertal-related changes that, in combination with social and psychological factors, can lead to long-lasting impairments in sleep health and affective functioning. Discrepant findings between subjective and objective measures of sleep in relation to affect have been reported in studies of adults; however, few investigations have assessed both subjective and objective sleep quality in a single sample, and fewer have examined this in the context of pubertal development. We aimed to (1) characterise pubertal associations with subjective sleep satisfaction, objective sleep efficiency, and objective and subjective sleep duration in adolescents; (2) examine the longitudinal association between daily affect and sleep metrics; and (3) test whether pubertal stage moderated this association. Eighty-nine participants (64% female, ages 13-20) completed an ecological momentary assessment (EMA) and actigraphy protocol. Independent of age, advanced pubertal stage was associated with lower subjective sleep satisfaction but not with objective sleep indices. Subjective sleep satisfaction was associated with within-person trajectories of negative affect, but not with positive affect. Pubertal stage and sleep satisfaction did not interact to predict within-day negative or positive affect. These findings are consistent with previous reports showing that objective and subjective sleep health are associated differently with puberty, and that subjective sleep health is associated with daily affect. Pubertal stage may be a more important indicator of subjective sleep quality in adolescence than is chronological age, most likely due to hormonal changes and psychological adjustment to the physical changes associated with the pubertal transition.

  View details for DOI 10.1111/jsr.13805

  View details for PubMedID 36514260

• Effects of the COVID-19 Pandemic on Mental Health and Brain Maturation in Adolescents: Implications for Analyzing Longitudinal Data. Biological psychiatry global open science Gotlib, I. H., Miller, J. G., Borchers, L. R., Coury, S. M., Costello, L. A., Garcia, J. M., Ho, T. C. 2022

  Abstract

  Background: The COVID-19 pandemic has caused significant stress and disruption for young people, likely leading to alterations in their mental health and neurodevelopment. In this context, it is not clear whether youth who lived through the pandemic and its shutdowns are comparable psychobiologically to their age- and sex-matched peers assessed before the pandemic. This question is particularly important for researchers who are analyzing longitudinal data that span the pandemic.Methods: In this study we compared carefully matched youth assessed before the pandemic (n=81) and after the pandemic-related shutdowns ended (n=82).Results: We found that youth assessed after the pandemic shutdowns had more severe internalizing mental health problems, reduced cortical thickness, larger hippocampal and amygdala volume, and more advanced brain age.Conclusions: Thus, not only does the COVID-19 pandemic appear to have led to poorer mental health and accelerated brain aging in adolescents, but it also poses significant challenges to researchers analyzing data from longitudinal studies of normative development that were interrupted by the pandemic.

  View details for DOI 10.1016/j.bpsgos.2022.11.002

  View details for PubMedID 36471743

• ADHD symptoms and diurnal cortisol in adolescents: The importance of comorbidities. Psychoneuroendocrinology Berens, A., LeMoult, J., Kircanski, K., Gotlib, I. H. 2022; 148: 105990

  Abstract

  Altered regulation of diurnal cortisol has been associated with both dimensional symptoms and clinical diagnoses of attention deficit-hyperactivity disorder (ADHD). Indeed, a recent meta-analysis suggests that lower diurnal cortisol output may be a biomarker of attention deficit-hyperactivity disorder (ADHD); importantly, however, the influence of psychiatric comorbidities on this association has not been characterized. Approximately two-thirds of children with ADHD have at least one co-occurring neuropsychiatric condition, and altered HPA-axis function has been implicated in many of these conditions. Using dimensional measures of psychopathology, we examined whether comorbid symptoms influence the association of ADHD symptoms with daily cortisol output.138 adolescents (ages 11-15 years) completed measures of symptoms of psychopathology and provided saliva samples over two days. We analyzed whether ADHD symptoms were related to morning, afternoon, and evening cortisol, the cortisol awakening response (CAR) and cumulative daily cortisol (area under the curve with respect to ground [AUCg]) while accounting for symptoms of three psychiatric disorders that are commonly comorbid with ADHD: conduct disorder (CD), anxiety, and depression. In sensitivity analyses, we included symptoms of oppositional defiant disorder (ODD) in place of CD symptoms.After controlling for symptoms of CD, anxiety, and depression, ADHD symptoms were associated significantly with higher cumulative diurnal cortisol (AUCg), morning cortisol, and afternoon cortisol. Symptoms of CD, anxiety and depression were not associated significantly with any cortisol metrics; however, in sensitivity analyses, ODD symptoms were associated with lower AUCg and morning cortisol.Our findings highlight the distinct influence of ADHD and externalizing symptoms on cortisol output. Further work is needed to examine the specificity of altered HPA-axis activity as a biomarker of ADHD and to elucidate whether symptoms of ADHD differ in their association with diurnal cortisol as a function of their severity.

  View details for DOI 10.1016/j.psyneuen.2022.105990

  View details for PubMedID 36462296

• Maternal-prenatal stress and depression predict infant temperament during the COVID-19 pandemic. Development and psychopathology Buthmann, J. L., Miller, J. G., Gotlib, I. H. 2022: 1-9

  Abstract

  Researchers have begun to examine the psychological toll of the ongoing global COVID-19 pandemic. Data are now emerging indicating that there may be long-term adverse effects of the pandemic on new mothers and on children born during this period. In a longitudinal study of maternal mental health and child emotional development during the pandemic, we conducted online assessments of a cohort of women at two time points: when they were pregnant at the beginning of the surge of the pandemic in the United States (baseline, N = 725), and approximately 1 year postpartum (follow-up, N = 296), examining prenatal and postnatal maternal mental health, prenatal pandemic-related stress, and infant temperament. Pandemic-related stress at baseline was associated with concurrent depressive symptoms and infant negative affect at follow-up. Baseline maternal depressive symptoms were associated with follow-up depressive symptoms, which in turn were also associated with infant negative affect. Pandemic-related stress during pregnancy may have enduring effects on infant temperament. These findings have important implications for our understanding of the emotional development of children who were in utero during the COVID-19 pandemic.

  View details for DOI 10.1017/S0954579422001055

  View details for PubMedID 36345652

• Empathy for others versus for one's child: Associations with mothers' brain activation during a social cognitive task and with their toddlers' functioning. Developmental psychobiology Ojha, A., Miller, J. G., King, L. S., Davis, E. G., Humphreys, K. L., Gotlib, I. H. 2022; 64 (7): e22313

  Abstract

  Caregivers who are higher in dispositional empathy tend to have children with better developmental outcomes; however, few studies have considered the role of child-directed (i.e., "parental") empathy, which may be relevant for the caregiver-child relationship. We hypothesized that mothers' parental empathy during their child's infancy will be a stronger predictor of their child's social-emotional functioning as a toddler than will mothers' dispositional empathy. We further explored whether parental and dispositional empathy have shared or distinct patterns of neural activation during a social-cognitive movie-watching task. In 118 mother-infant dyads, greater parental empathy assessed when infants were 6 months old was associated with more social-emotional competencies and fewer problems in the children 1 year later, even after adjusting for dispositional empathy. In contrast, dispositional empathy was not associated with child functioning when controlling for parental empathy. In a subset of 20 mothers, insula activation was positively associated with specific facets of both dispositional and parental empathy, whereas right temporoparietal junction activation was associated only with parental empathy. Thus, dispositional and parental empathy appear to be dissociable by both brain and behavioral metrics. Parental empathy may be a viable target for interventions, especially for toddlers at risk for developing social-emotional difficulties.

  View details for DOI 10.1002/dev.22313

  View details for PubMedID 36282757

  View details for PubMedCentralID PMC9608359

• Negative caregiving and stress reactivity moderate the relation between early life stress and externalizing in adolescence DEVELOPMENTAL PSYCHOBIOLOGY Buthmann, J., Miller, J. G., Chahal, R., Berens, A., Gotlib, I. H. 2022; 64 (7)

  View details for DOI 10.1002/dev.22327

  View details for Web of Science ID 000862011900001

• Empathy for others versus for one's child: Associations with mothers' brain activation during a social cognitive task and with their toddlers' functioning DEVELOPMENTAL PSYCHOBIOLOGY Ojha, A., Miller, J. G., King, L. S., Davis, E. G., Humphreys, K. L., Gotlib, I. H. 2022; 64 (7)

  View details for DOI 10.1002/dev.22313

  View details for Web of Science ID 000828228600001

• An exploratory analysis of leukocyte telomere length among pregnant and non-pregnant people. Brain, behavior, & immunity - health Panelli, D. M., Diwan, M., Cruz, G. I., Leonard, S. A., Chueh, J., Gotlib, I. H., Bianco, K. 2022; 25: 100506

  Abstract

  Background: Leukocyte telomere length (LTL) is a biomarker that is affected by older age, psychosocial stress, and medical comorbidities. Despite the relevance of these factors to obstetric practice, little is known about LTL in pregnancy. Our study explored longitudinal LTL dynamics in pregnant and non-pregnant people.Objective: This pilot study compares changes in LTL between pregnant and non-pregnant people over time, explores potential correlations between LTL and mental health measures, and investigates associations between short first-trimester LTL and adverse pregnancy outcomes.Study design: This was a prospective pilot cohort study of nulliparous pregnant and non-pregnant people between ages 18 and 50 who presented for care at a single institution from January to November 2020. Pregnant people were enrolled between 10 and 14 weeks gestation. Participants had two blood samples drawn for LTL; the first on the day of enrollment and the second on postpartum day 1 (pregnant cohort) or 7 months later (non-pregnant cohort). LTL was measured using quantitative PCR. The primary outcome was the difference between pregnant and non-pregnant people in LTL change between the two timepoints (basepair difference per 30-day period). Secondary outcomes included differences in responses to the Patient Health Questionnaire-9 (PHQ-9) and a survey about stress related to COVID-19. Differences in LTL were tested using t-tests and linear regression models, both crude and adjusted for age. A subgroup analysis was conducted within the pregnant cohort to examine whether shorter first-trimester LTL was associated with adverse pregnancy outcomes. We conducted t-tests to compare LTL between people with and without each categorical outcome and computed Pearson correlation coefficients between LTL and continuous outcomes such as gestational age at delivery.Results: 46 pregnant and 30 non-pregnant people were enrolled; 44 pregnant and 18 non-pregnant people completed all LTL assessments. There were no between-group differences in LTL change (-4.2±22.2 bp per 30 days pregnant versus -6.4±11.2 bp per 30 days non-pregnant, adjusted beta 2.1, 95% CI -9.0-13.2, p=0.60). The prevalence of depression and pandemic-related stress were both low overall. The two groups did not differ in PHQ-9 scores, and no correlations were significant between LTL and PHQ-9 scores. Among the 44 pregnant people, shorter first-trimester LTL was significantly correlated with earlier gestational age at delivery (r=0.35, p=0.02).Conclusion: In this exploratory pilot cohort of reproductive-aged people with low levels of psychological stress, we described baseline changes in LTL over time in pregnant and non-pregnant participants. We found a correlation between shorter first-trimester LTL and earlier gestational age at delivery, which warrants further investigation in a larger cohort.

  View details for DOI 10.1016/j.bbih.2022.100506

  View details for PubMedID 36110146

• Negative caregiving and stress reactivity moderate the relation between early life stress and externalizing in adolescence. Developmental psychobiology Buthmann, J., Miller, J. G., Chahal, R., Berens, A., Gotlib, I. H. 2022; 64 (7): e22327

  Abstract

  Exposure to early life stress (ELS) is common and has been implicated in the development of psychopathology; importantly, however, many individuals who experience ELS do not develop emotional or behavioral difficulties. Prior research implicates stress exposure, negative caregiving behaviors, and patterns of physiological reactivity in predicting psychological well-being; however, the precise factors that contribute to resilience versus vulnerability to the adverse effects of stress exposures are not well understood. In a longitudinal study of adolescents (N = 120) assessed at three timepoints approximately every 2 years beginning at the ages of 913 years, we examined the roles of autonomic reactivity to social stress (assessed through skin conductance during the Trier Social Stress Task) and negative caregiving behaviors as moderators of the association between exposure to ELS and internalizing and externalizing symptoms. We found that the relation between ELS and externalizing symptoms was moderated by both negative caregiving and autonomic reactivity, such that the relation between ELS and externalizing was positive at low levels of negative caregiving and at high levels of autonomic reactivity; interactions predicting internalizing symptoms were not statistically significant. These findings highlight the importance of considering physiological and environmental variables that might contribute to susceptibility or resilience to symptoms of psychopathology following exposure to ELS.

  View details for DOI 10.1002/dev.22327

  View details for PubMedID 36282754

  View details for PubMedCentralID PMC9608333

• Social threat, fronto-cingulate-limbic morphometry, and symptom course in depressed adolescents: a longitudinal investigation. Psychological medicine Ojha, A., Teresi, G. I., Slavich, G. M., Gotlib, I. H., Ho, T. C. 2022: 1-15

  Abstract

  BACKGROUND: Psychosocial stressors characterized by social threat, such as interpersonal loss and social rejection, are associated with depression in adolescents. Few studies, however, have examined whether social threat affects fronto-cingulate-limbic systems implicated in adolescent depression.METHODS: We assessed lifetime stressor severity across several domains using the Stress and Adversity Inventory (STRAIN) in 57 depressed adolescents (16.15 ± 1.32 years, 34 females), and examined whether the severity of social threat and non-social threat stressors was associated with gray matter volumes (GMVs) in the anterior cingulate cortex (ACC), amygdala, hippocampus, and nucleus accumbens (NAcc). We also examined how lifetime social threat severity and GMVs in these regions related to depressive symptoms at baseline and over 9 months.RESULTS: General stressor severity was related to greater depression severity at baseline and over 9 months. Moreover, greater severity of social threat (but not non-social threat) stressors was associated with smaller bilateral amygdala and NAcc GMVs, and smaller bilateral surface areas of caudal and rostral ACC (all pFDR ⩽ 0.048). However, neither social threat nor non-social threat stressor severity was related to hippocampal GMVs (all pFDR ⩾ 0.318). All fronto-cingulate-limbic structures that were associated with the severity of social threat were negatively associated with greater depression severity over 9 months (all pFDR ⩽ 0.014). Post-hoc analyses suggested that gray matter morphometry of bilateral amygdala, NAcc, and rostral and caudal ACC mediated the association between social threat and depression severity in adolescents over 9 months (all pFDR < 0.048).CONCLUSIONS: Social threat specifically affects fronto-cingulate-limbic pathways that contribute to the maintenance of depression in adolescents.

  View details for DOI 10.1017/S0033291722002239

  View details for PubMedID 36117278

• Structural brain alterations associated with suicidal thoughts and behaviors in young people: results from 21 international studies from the ENIGMA Suicidal Thoughts and Behaviours consortium. Molecular psychiatry van Velzen, L. S., Dauvermann, M. R., Colic, L., Villa, L. M., Savage, H. S., Toenders, Y. J., Zhu, A. H., Bright, J. K., Campos, A. I., Salminen, L. E., Ambrogi, S., Ayesa-Arriola, R., Banaj, N., Basgoze, Z., Bauer, J., Blair, K., Blair, R. J., Brosch, K., Cheng, Y., Colle, R., Connolly, C. G., Corruble, E., Couvy-Duchesne, B., Crespo-Facorro, B., Cullen, K. R., Dannlowski, U., Davey, C. G., Dohm, K., Fullerton, J. M., Gonul, A. S., Gotlib, I. H., Grotegerd, D., Hahn, T., Harrison, B. J., He, M., Hickie, I. B., Ho, T. C., Iorfino, F., Jansen, A., Jollant, F., Kircher, T., Klimes-Dougan, B., Klug, M., Leehr, E. J., Lippard, E. T., McLaughlin, K. A., Meinert, S., Miller, A. B., Mitchell, P. B., Mwangi, B., Nenadic, I., Ojha, A., Overs, B. J., Pfarr, J., Piras, F., Ringwald, K. G., Roberts, G., Romer, G., Sanches, M., Sheridan, M. A., Soares, J. C., Spalletta, G., Stein, F., Teresi, G. I., Tordesillas-Gutierrez, D., Uyar-Demir, A., van der Wee, N. J., van der Werff, S. J., Vermeiren, R. R., Winter, A., Wu, M., Yang, T. T., Thompson, P. M., Renteria, M. E., Jahanshad, N., Blumberg, H. P., van Harmelen, A., ENIGMA Suicidal Thoughts and Behaviours Consortium, Schmaal, L., van Velzen, L. S., van der Wee, N. J., van der Werff, S. J., van Harmelen, A. 2022

  Abstract

  Identifying brain alterations associated with suicidal thoughts and behaviors (STBs) in young people is critical to understanding their development and improving early intervention and prevention. The ENIGMA Suicidal Thoughts and Behaviours (ENIGMA-STB) consortium analyzed neuroimaging data harmonized across sites to examine brain morphology associated with STBs in youth. We performed analyses in three separate stages, in samples ranging from most to least homogeneous in terms of suicide assessment instrument and mental disorder. First, in a sample of 577 young people with mood disorders, in which STBs were assessed with the Columbia Suicide Severity Rating Scale (C-SSRS). Second, in a sample of young people with mood disorders, in which STB were assessed using different instruments, MRI metrics were compared among healthy controls without STBs (HC; N=519), clinical controls with a mood disorder but without STBs (CC; N=246) and young people with current suicidal ideation (N=223). In separate analyses, MRI metrics were compared among HCs (N=253), CCs (N=217), and suicide attempters (N=64). Third, in a larger transdiagnostic sample with various assessment instruments (HC=606; CC=419; Ideation=289; HC=253; CC=432; Attempt=91). In the homogeneous C-SSRS sample, surface area of the frontal pole was lower in young people with mood disorders and a history of actual suicide attempts (N=163) than those without a lifetime suicide attempt (N=323; FDR-p=0.035, Cohen's d=0.34). No associations with suicidal ideation were found. When examining more heterogeneous samples, we did not observe significant associations. Lower frontal pole surface area may represent a vulnerability for a (non-interrupted and non-aborted) suicide attempt; however, more research is needed to understand the nature of its relationship to suicide risk.

  View details for DOI 10.1038/s41380-022-01734-0

  View details for PubMedID 36071108

• Geotemporal analysis of perinatal care changes and maternal mental health: an example from the COVID-19 pandemic. Archives of women's mental health Hendrix, C. L., Werchan, D., Lenniger, C., Ablow, J. C., Amstadter, A. B., Austin, A., Babineau, V., Bogat, G. A., Cioffredi, L., Conradt, E., Crowell, S. E., Dumitriu, D., Elliott, A. J., Fifer, W., Firestein, M., Gao, W., Gotlib, I., Graham, A., Gregory, K. D., Gustafsson, H., Havens, K. L., Hockett, C., Howell, B. R., Humphreys, K. L., Jallo, N., King, L. S., Kinser, P. A., Levendosky, A. A., Lonstein, J. S., Lucchini, M., Marcus, R., Monk, C., Moyer, S., Muzik, M., Nuttall, A. K., Potter, A. S., Rogers, C., Salisbury, A., Shuffrey, L. C., Smith, B. A., Smyser, C. D., Smith, L., Sullivan, E., Zhou, J., Brito, N. H., Thomason, M. E. 2022

  Abstract

  Our primary objective was to document COVID-19 induced changes to perinatal care across the USA and examine the implication of these changes for maternal mental health. We performed an observational cross-sectional study with convenience sampling using direct patient reports from 1918 postpartum and 3868 pregnant individuals collected between April 2020 and December 2020 from 10 states across the USA. We leverage a subgroup of these participants who gave birth prior to March 2020 to estimate the pre-pandemic prevalence of specific birthing practices as a comparison. Our primary analyses describe the prevalence and timing of perinatal care changes, compare perinatal care changes depending on when and where individuals gave birth, and assess the linkage between perinatal care alterations and maternal anxiety and depressive symptoms. Seventy-eight percent of pregnant participants and 63% of postpartum participants reported at least one change to their perinatal care between March and August 2020. However, the prevalence and nature of specific perinatal care changes occurred unevenly over time and across geographic locations. The separation of infants and mothers immediately after birth and the cancelation of prenatal visits were associated with worsened depression and anxiety symptoms in mothers after controlling for sociodemographic factors, mental health history, number of pregnancy complications, and general stress about the COVID-19 pandemic. Our analyses reveal widespread changes to perinatal care across the US that fluctuated depending on where and when individuals gave birth. Disruptions to perinatal care may also exacerbate mental health concerns, so focused treatments that can mitigate the negative psychiatric sequelae of interrupted care are warranted.

  View details for DOI 10.1007/s00737-022-01252-6

  View details for PubMedID 35962855

• The Role of Educational Attainment and Brain Morphology in Major Depressive Disorder: Findings From the ENIGMA Major Depressive Disorder Consortium JOURNAL OF PSYCHOPATHOLOGY AND CLINICAL SCIENCE Whittle, S., Rakesh, D., Schmaal, L., Veltman, D. J., Thompson, P. M., Singh, A., Gonul, A., Aleman, A., Demir, A., Krug, A., Mwangi, B., Kramer, B., Baune, B. T., Stein, D. J., Grotegerd, D., Pomarol-Clotet, E., Rodriguez-Cano, E., Melloni, E., Benedetti, F., Stein, F., Grabe, H. J., Volzke, H., Gotlib, I. H., Nenadic, I., Soares, J. C., Repple, J., Sim, K., Brosch, K., Wittfeld, K., Berger, K., Hermesdorf, M., Portella, M. J., Sacchet, M. D., Wu, M., Opel, N., Groenewold, N. A., Gruber, O., Fuentes-Claramonte, P., Salvador, R., Goya-Maldonado, R., Sarro, S., Poletti, S., Meinert, S. L., Kircher, T., Dannlowski, U., Pozzi, E. 2022; 131 (6): 664-673

  Abstract

  Brain structural abnormalities and low educational attainment are consistently associated with major depressive disorder (MDD), yet there has been little research investigating the complex interaction of these factors. Brain structural alterations may represent a vulnerability or differential susceptibility marker, and in the context of low educational attainment, predict MDD. We tested this moderation model in a large multisite sample of 1958 adults with MDD and 2921 controls (aged 18 to 86) from the ENIGMA MDD working group. Using generalized linear mixed models and within-sample split-half replication, we tested whether brain structure interacted with educational attainment to predict MDD status. Analyses revealed that cortical thickness in a number of occipital, parietal, and frontal regions significantly interacted with education to predict MDD. For the majority of regions, models suggested a differential susceptibility effect, whereby thicker cortex was more likely to predict MDD in individuals with low educational attainment, but less likely to predict MDD in individuals with high educational attainment. Findings suggest that greater thickness of brain regions subserving visuomotor and social-cognitive functions confers susceptibility to MDD, dependent on level of educational attainment. Longitudinal work, however, is ultimately needed to establish whether cortical thickness represents a preexisting susceptibility marker. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

  View details for DOI 10.1037/abn0000738

  View details for Web of Science ID 000969034600016

  View details for PubMedID 35653754

• Early life stress, systemic inflammation, and neural correlates of implicit emotion regulation in adolescents. Brain, behavior, and immunity Yuan, J. P., Ho, T. C., Coury, S. M., Chahal, R., Colich, N. L., Gotlib, I. H. 2022

  Abstract

  Exposure to early life stress (ELS) increases the risk for developing psychopathology; however, the mechanisms underlying this association are not clear. In this study we examined systemic inflammation as a pathway that may link exposure to stress to altered neural correlates of implicit emotion regulation in adolescents with varying levels of exposure to ELS (n=83; 52 females, 31 males; 15.63±1.10 years). We measured ventrolateral prefrontal cortex (vlPFC) activation and functional connectivity (FC) between the bilateral amygdala and the vlPFC as adolescents completed an affect labeling task in the scanner and assessed concentrations of C-reactive protein (CRP) using a dried blood spot protocol. We found that CRP levels were negatively associated with vlPFC activation during implicit regulation of negatively-valenced stimuli, and that cumulative severity of ELS exposure moderated this neuroimmune association. Severity of ELS also significantly moderated the association between CRP levels and FC between the bilateral amygdala and L-vlPFC during implicit emotion regulation: in adolescents who had been exposed to more severe ELS, higher CRP was associated with more negative frontoamygdala FC during implicit regulation of negatively-valenced stimuli. Thus, ELS may disrupt the normative association between the immune system and the neural processes that underlie socioemotional functioning potentially increasing adolescents' risk for maladaptive outcomes.

  View details for DOI 10.1016/j.bbi.2022.07.007

  View details for PubMedID 35842188

• A Social Gradient of Cortical Thickness in Adolescence: Relationships With Neighborhood Socioeconomic Disadvantage, Family Socioeconomic Status, and Depressive Symptoms. Biological psychiatry global open science Miller, J. G., Lopez, V., Buthmann, J. L., Garcia, J. M., Gotlib, I. H. 2022; 2 (3): 253-262

  Abstract

  BACKGROUND: Mental and physical health are affected by family and neighborhood socioeconomic status (SES). Accelerated maturation in the context of lower SES is one mechanism that might contribute to underlying health disparities; few studies, however, have considered neighborhood SES in relation to putative markers of brain maturation in adolescents.METHODS: In 120 adolescents 13 to 18 years of age, we examined family and neighborhood SES in relation to cortical thickness adjusted for age. We also examined whether cortical thickness was related to depressive symptoms and explored regions of interest.RESULTS: Controlling for age, neighborhood socioeconomic disadvantage was associated with a thinner cortex in the left hemisphere (standardized beta = -0.20), which was related to more severe depressive symptoms (standardized beta = -0.33). Family SES was not significantly associated with age-adjusted mean cortical thickness in either hemisphere after controlling for relevant covariates. In exploratory, covariate-adjusted analyses of cortical thickness at the regional level, neighborhood socioeconomic disadvantage was associated with reduced cortical thickness in the left superior frontal gyrus (standardized beta = -0.27), fusiform gyrus (standardized beta = -0.20), and insula (standardized beta = -0.21), whereas family SES was positively associated with cortical thickness in the right lateral and right medial orbitofrontal cortex (standardized beta = 0.21 and standardized beta = 0.19, respectively) and left transverse temporal gyrus (standardized beta = 0.22).CONCLUSIONS: Our findings provide evidence for a social gradient of cortical thickness during adolescence. Adolescents living in less advantaged community or family contexts appear to have a thinner cortex according to global and regional measures. Reduced cortical thickness in the left hemisphere may indicate increased risk for depression in adolescence.

  View details for DOI 10.1016/j.bpsgos.2022.03.005

  View details for PubMedID 36032055

• Infants who experience more adult-initiated conversations have better expressive language in toddlerhood. Infancy : the official journal of the International Society on Infant Studies Salo, V. C., King, L. S., Gotlib, I. H., Humphreys, K. L. 2022

  Abstract

  To understand how infants become engaged in conversations with their caregivers, we examined who tends to initiate conversations between adults and infants, differences between the features of infant- and adult-initiated conversations, and whether individual differences in how much infants engage in infant- or adult-initiated conversations uniquely predict later language development. We analyzed naturalistic adult-infant conversations captured via passive recording of the daily environment in two samples of 6-month-old infants. In Study 1, we found that at age 6months, infants typically engage in more adult- than infant-initiated conversations and that adult-initiated conversations are, on average, longer and contain more adult words. In Study 2, we replicated these findings and, further, found that infants who engaged in more adult-initiated conversations in infancy had better expressive language at age 18months. This association remained significant when accounting for the number of infant-initiated conversations at 6months. Our findings indicate that early interactions with caregivers can have a lasting impact on children's language development, and that the extent to which parents initiate interactions with their infants may be particularly important.

  View details for DOI 10.1111/infa.12487

  View details for PubMedID 35775622

• Hippocampal volume indexes neurobiological sensitivity to the effect of pollution burden on telomere length in adolescents. New directions for child and adolescent development Miller, J. G., Buthmann, J. L., Gotlib, I. H. 2022

  Abstract

  Exposure to environmental pollutants has been associated with cellular aging in children and adolescents. Individuals may vary, however, in their sensitivity or vulnerability to the effects of environmental pollutants. Larger hippocampal volume has emerged as a potential index of increased sensitivity to social contexts. In exploratory analyses (N=214), we extend work in this area by providing evidence that larger hippocampal volume in early adolescence reflects increased sensitivity to the effect of neighborhood pollution burden on telomere length (standardized beta =-0.40, 95% CI[-0.65, -0.15]). In contrast, smaller hippocampal volume appears to buffer this association (standardized beta =0.02). In youth with larger hippocampal volume, pollution burden was indirectly associated with shorter telomere length approximately 2 years later through shorter telomere length at baseline (indirect standardized beta =-0.25, 95% CI[-0.40, 0.10]). For these youth, living in high or low pollution-burdened neighborhoods may predispose them to develop shorter or longer telomeres, respectively, later in adolescence.

  View details for DOI 10.1002/cad.20471

  View details for PubMedID 35738556

• Detecting negative valence symptoms in adolescents based on longitudinal self-reports and behavioral assessments. Journal of affective disorders Paschali, M., Kiss, O., Zhao, Q., Adeli, E., Podhajsky, S., Muller-Oehring, E. M., Gotlib, I. H., Pohl, K. M., Baker, F. C. 2022

  Abstract

  BACKGROUND: Given the high prevalence of depressive symptoms reported by adolescents and associated risk of experiencing psychiatric disorders as adults, differentiating the trajectories of the symptoms related to negative valence at an individual level could be crucial in gaining a better understanding of their effects later in life.METHODS: A longitudinal deep learning framework is presented, identifying self-reported and behavioral measurements that detect the depressive symptoms associated with the Negative Valence System domain of the NIMH Research Domain Criteria (RDoC).RESULTS: Applied to the annual records of 621 participants (age range: 12 to 17 years) of the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA), the deep learning framework identifies predictors of negative valence symptoms, which include lower extraversion, poorer sleep quality, impaired executive control function and factors related to substance use.LIMITATIONS: The results rely mainly on self-reported measures and do not provide information about the underlying neural correlates. Also, a larger sample is required to understand the role of sex and other demographics related to the risk of experiencing symptoms of negative valence.CONCLUSIONS: These results provide new information about predictors of negative valence symptoms in individuals during adolescence that could be critical in understanding the development of depression and identifying targets for intervention. Importantly, findings can inform preventive and treatment approaches for depression in adolescents, focusing on a unique predictor set of modifiable modulators to include factors such as sleep hygiene training, cognitive-emotional therapy enhancing coping and controllability experience and/or substance use interventions.

  View details for DOI 10.1016/j.jad.2022.06.002

  View details for PubMedID 35688394

• Maternal attachment insecurity, maltreatment history, and depressive symptoms are associated with broad DNA methylation signatures in infants. Molecular psychiatry Robakis, T. K., Roth, M. C., King, L. S., Humphreys, K. L., Ho, M., Zhang, X., Chen, Y., Li, T., Rasgon, N. L., Watson, K. T., Urban, A. E., Gotlib, I. H. 2022

  Abstract

  The early environment, including maternal characteristics, provides many cues to young organisms that shape their long-term physical and mental health. Identifying the earliest molecular events that precede observable developmental outcomes could help identify children in need of support prior to the onset of physical and mental health difficulties. In this study, we examined whether mothers' attachment insecurity, maltreatment history, and depressive symptoms were associated with alterations in DNA methylation patterns in their infants, and whether these correlates in the infant epigenome were associated with socioemotional and behavioral functioning in toddlerhood. We recruited 156 women oversampled for histories of depression, who completed psychiatric interviews and depression screening during pregnancy, then provided follow-up behavioral data on their children at 18 months. Buccal cell DNA was obtained from 32 of their infants for a large-scale analysis of methylation patterns across 5 × 106 individual CpG dinucleotides, using clustering-based significance criteria to control for multiple comparisons. We found that tens of thousands of individual infant CpGs were alternatively methylated in association with maternal attachment insecurity, maltreatment in childhood, and antenatal and postpartum depressive symptoms, including genes implicated in developmental patterning, cell-cell communication, hormonal regulation, immune function/inflammatory response, and neurotransmission. Density of DNA methylation at selected genes from the result set was also significantly associated with toddler socioemotional and behavioral problems. This is the first report to identify novel regions of the human infant genome at which DNA methylation patterns are associated longitudinally both with maternal characteristics and with offspring socioemotional and behavioral problems in toddlerhood.

  View details for DOI 10.1038/s41380-022-01592-w

  View details for PubMedID 35577912

• Leukocyte telomere dynamics across gestation in uncomplicated pregnancies and associations with stress. BMC pregnancy and childbirth Panelli, D. M., Leonard, S. A., Wong, R. J., Becker, M., Mayo, J. A., Wu, E., Girsen, A. I., Gotlib, I. H., Aghaeepour, N., Druzin, M. L., Shaw, G. M., Stevenson, D. K., Bianco, K. 2022; 22 (1): 381

  Abstract

  Short leukocyte telomere length is a biomarker associated with stress and morbidity in non-pregnant adults. Little is known, however, about maternal telomere dynamics in pregnancy. To address this, we examined changes in maternal leukocyte telomere length (LTL) during uncomplicated pregnancies and explored correlations with perceived stress.In this pilot study, maternal LTL was measured in blood collected from nulliparas who delivered live, term, singleton infants between 2012 and 2018 at a single institution. Participants were excluded if they had diabetes or hypertensive disease. Samples were collected over the course of pregnancy and divided into three time periods: < 200/7 weeks (Timepoint 1); 201/7 to 366/7 weeks (Timepoint 2); and 370/7 to 9-weeks postpartum (Timepoint 3). All participants also completed a survey assessing a multivariate profile of perceived stress at the time of enrollment in the first trimester. LTL was measured using quantitative polymerase chain reaction (PCR). Wilcoxon signed-rank tests were used to compare LTL differences within participants across all timepoint intervals. To determine whether mode of delivery affected LTL, we compared postpartum Timepoint 3 LTLs between participants who had vaginal versus cesarean birth. Secondarily, we evaluated the association of the assessed multivariate stress profile and LTL using machine learning analysis.A total of 115 samples from 46 patients were analyzed. LTL (mean ± SD), expressed as telomere to single copy gene (T/S) ratios, were: 1.15 ± 0.26, 1.13 ± 0.23, and 1.07 ± 0.21 for Timepoints 1, 2, and 3, respectively. There were no significant differences in LTL between Timepoints 1 and 2 (LTL T/S change - 0.03 ± 0.26, p = 0.39); 2 and 3 (- 0.07 ± 0.29, p = 0.38) or Timepoints 1 and 3 (- 0.07 ± 0.21, p = 0.06). Participants who underwent cesareans had significantly shorter postpartum LTLs than those who delivered vaginally (T/S ratio: 0.94 ± 0.12 cesarean versus 1.12 ± 0.21 vaginal, p = 0.01). In secondary analysis, poor sleep quality was the main stress construct associated with shorter Timepoint 1 LTLs (p = 0.02) and shorter mean LTLs (p = 0.03).In this cohort of healthy pregnancies, maternal LTLs did not significantly change across gestation and postpartum LTLs were shorter after cesarean than after vaginal birth. Significant associations between sleep quality and short LTLs warrant further investigation.

  View details for DOI 10.1186/s12884-022-04693-0

  View details for PubMedID 35501726

• Validation of the Assessment of Parent and Child Adversity (APCA) in Mothers and Young Children. Journal of clinical child and adolescent psychology : the official journal for the Society of Clinical Child and Adolescent Psychology, American Psychological Association, Division 53 King, L. S., Humphreys, K. L., Shaw, G. M., Stevenson, D. K., Gotlib, I. H. 2022: 1-16

  Abstract

  Advancing understanding of how early adversity arises, manifests, and contributes to health difficulties depends on accurate measurement of children's experiences. In early life, exposure to adversity is often intertwined with that of one's caregivers. We present preliminary psychometric properties of a novel measure of adversity, the Assessment of Parent and Child Adversity (APCA), which simultaneously characterizes parents' and children's adversity.During pregnancy, women reported their past adverse experiences. When their children were ages 3-5 years (47% female), 97 mothers (71% White, 17% Hispanic/Latinx) completed the APCA, the Childhood Trauma Questionnaire, and the Benevolent Childhood Experiences scale. They reported their current symptoms of depression and anxiety and their child's emotional and behavioral problems. Using the APCA, we distinguished between maternal adversity during different life periods and obtained metrics of child witnessing of and direct exposure to adversity.The APCA demonstrated validity with other measures of maternal adverse experiences, maternal positive childhood experiences, and maternal symptoms of psychopathology. Children whose mothers experienced greater adversity, particularly in the prenatal period, had more emotional and behavioral problems, as did children who were directly exposed to greater adversity.The APCA has good usability and validity. Leveraging the ability of the APCA to distinguish between adversity during different life stages and originating from different sources, our findings highlight potentially distinct effects of different aspects of maternal and child adversity on difficulties in maternal and child mental health.

  View details for DOI 10.1080/15374416.2022.2042696

  View details for PubMedID 35500216

• The Intriguing Role of Thalamic Structure and Function in Youth With and at Familial Risk for Bipolar Disorder Singh, M., Gorelik, A., Gorelik, M., Chang, K., Gotlib, I., Reiss, A., Nimarko, A. ELSEVIER SCIENCE INC. 2022: S38

  View details for Web of Science ID 000789022200095

• Trajectories of Depressive Symptoms and Reward Circuitry in Adolescence Following Early Life Stress: A Longitudinal Assessment Borchers, L., Yuan, J., Chahal, R., Ryu, J., Colich, N., Gotlib, I. ELSEVIER SCIENCE INC. 2022: S79

  View details for Web of Science ID 000789022200195

• Dimensions of Early Adversity and the Development of Functional Brain Network Connectivity During Adolescence: Implications for Trajectories of Internalizing Symptoms Chahal, R., Miller, J. G., Yuan, J. P., Buthmann, J. L., Ho, T. C., Gotlib, I. H. ELSEVIER SCIENCE INC. 2022: S48

  View details for Web of Science ID 000789022200122

• Prenatal COVID-19 Related Stress, Maternal Emotion Regulation and Infant Temperament: Assessing the Developmental Impact of the COVID-19 Pandemic Costello, L., Buthmann, J. L., Gotlib, I. ELSEVIER SCIENCE INC. 2022: S253

  View details for Web of Science ID 000789022200620

• Childhood Emotional Abuse is Associated with Delayed Brain Age in Depressed Adolescents Lopez, V., Jonas, M. G., Gotlib, I. H., Ho, T. ELSEVIER SCIENCE INC. 2022: S228

  View details for Web of Science ID 000789022200559

• Coping During the COVID-19 Pandemic: Maternal Mental Health and Infant Temperament Buthmann, J., Coury, S., Gotlib, I. ELSEVIER SCIENCE INC. 2022: S196-S197

  View details for Web of Science ID 000789022200480

• COVID-19 stressors, mental/emotional distress and political support WEST EUROPEAN POLITICS Bernardi, L., Gotlib, I. H. 2022

  View details for DOI 10.1080/01402382.2022.2055372

  View details for Web of Science ID 000778481800001

• Intrinsic connectivity and family dynamics: Striato-limbic markers of risk and resilience in youth at familial risk for mood disorders. Biological psychiatry. Cognitive neuroscience and neuroimaging Fischer, A. S., Holt-Gosselin, B., Hagan, K. E., Fleming, S. L., Nimarko, A. F., Gotlib, I. H., Singh, M. K. 2022

  Abstract

  BACKGROUND: Characterizing (1) functional connectivity (FC) markers of risk and resilience in emotion and reward networks and (2) how family dynamics in youth at high familial risk for bipolar disorder (HR-BD) and major depressive disorder (HR-MDD) are related to FC may advance our understanding of the neural underpinnings of mood disorders and lead to more effective interventions.METHODS: 139 youth (43 HR-BD, 46 HR-MDD, and 50 low risk [LR]) aged 12.9+/-2.7 years were followed for 4.5+/-2.4 years. We characterized differences in striato-limbic FC that distinguished HR-BD, HR-MDD and LR; and resilience (RES) versus conversion to psychopathology (CVT). We then examined whether risk status moderated FC-family function associations. Finally, we examined whether baseline differences in FC between HR-BD, HR-MDD and LR predicted RES versus CVT at follow-up.RESULTS: HR-BD had greater amygdala-middle frontal gyrus and dorsal striatum-middle frontal gyrus FC, and HR-MDD had lower amygdala-fusiform gyrus and dorsal striatum-precentral gyrus FC (voxel-level p<0.001, cluster-level FDR-corrected p<0.05). RES had greater amygdala-orbitofrontal cortex and ventral striatum-dorsal anterior cingulate cortex FC relative to CVT (voxel-level p<0.001, cluster-level FDR-corrected p<0.05). Greater family rigidity was inversely associated with amygdala-fusiform gyrus FC across all groups (FDR-corrected p=0.017), with a moderating effect of bipolar risk status (HR-BD vs. HR-MDD p<0.001; HR-BD versus LR p=0.005). Baseline FC differences did not predict RES versus CVT.CONCLUSIONS: Findings represent neural signatures of risk and resilience in emotion and reward processing networks in youth at familial risk for mood disorders that may be targets for novel interventions tailored to the family context.

  View details for DOI 10.1016/j.bpsc.2022.02.009

  View details for PubMedID 35272095

• Virtual Ontogeny of Cortical Growth Preceding Mental Illness. Biological psychiatry Patel, Y., Shin, J., Abé, C., Agartz, I., Alloza, C., Alnæs, D., Ambrogi, S., Antonucci, L. A., Arango, C., Arolt, V., Auzias, G., Ayesa-Arriola, R., Banaj, N., Banaschewski, T., Bandeira, C., Başgöze, Z., Cupertino, R. B., Bau, C. H., Bauer, J., Baumeister, S., Bernardoni, F., Bertolino, A., Bonnin, C. D., Brandeis, D., Brem, S., Bruggemann, J., Bülow, R., Bustillo, J. R., Calderoni, S., Calvo, R., Canales-Rodríguez, E. J., Cannon, D. M., Carmona, S., Carr, V. J., Catts, S. V., Chenji, S., Chew, Q. H., Coghill, D., Connolly, C. G., Conzelmann, A., Craven, A. R., Crespo-Facorro, B., Cullen, K., Dahl, A., Dannlowski, U., Davey, C. G., Deruelle, C., Díaz-Caneja, C. M., Dohm, K., Ehrlich, S., Epstein, J., Erwin-Grabner, T., Eyler, L. T., Fedor, J., Fitzgerald, J., Foran, W., Ford, J. M., Fortea, L., Fuentes-Claramonte, P., Fullerton, J., Furlong, L., Gallagher, L., Gao, B., Gao, S., Goikolea, J. M., Gotlib, I., Goya-Maldonado, R., Grabe, H. J., Green, M., Grevet, E. H., Groenewold, N. A., Grotegerd, D., Gruber, O., Haavik, J., Hahn, T., Harrison, B. J., Heindel, W., Henskens, F., Heslenfeld, D. J., Hilland, E., Hoekstra, P. J., Hohmann, S., Holz, N., Howells, F. M., Ipser, J. C., Jahanshad, N., Jakobi, B., Jansen, A., Janssen, J., Jonassen, R., Kaiser, A., Kaleda, V., Karantonis, J., King, J. A., Kircher, T., Kochunov, P., Koopowitz, S. M., Landén, M., Landrø, N. I., Lawrie, S., Lebedeva, I., Luna, B., Lundervold, A. J., MacMaster, F. P., Maglanoc, L. A., Mathalon, D. H., McDonald, C., McIntosh, A., Meinert, S., Michie, P. T., Mitchell, P., Moreno-Alcázar, A., Mowry, B., Muratori, F., Nabulsi, L., Nenadić, I., O'Gorman Tuura, R., Oosterlaan, J., Overs, B., Pantelis, C., Parellada, M., Pariente, J. C., Pauli, P., Pergola, G., Piarulli, F. M., Picon, F., Piras, F., Pomarol-Clotet, E., Pretus, C., Quidé, Y., Radua, J., Ramos-Quiroga, J. A., Rasser, P. E., Reif, A., Retico, A., Roberts, G., Rossell, S., Rovaris, D. L., Rubia, K., Sacchet, M., Salavert, J., Salvador, R., Sarró, S., Sawa, A., Schall, U., Scott, R., Selvaggi, P., Silk, T., Sim, K., Skoch, A., Spalletta, G., Spaniel, F., Stein, D. J., Steinsträter, O., Stolicyn, A., Takayanagi, Y., Tamm, L., Tavares, M., Teumer, A., Thiel, K., Thomopoulos, S. I., Tomecek, D., Tomyshev, A. S., Tordesillas-Gutiérrez, D., Tosetti, M., Uhlmann, A., Van Rheenen, T., Vazquez-Bourgón, J., Vernooij, M. W., Vieta, E., Vilarroya, O., Weickert, C., Weickert, T., Westlye, L. T., Whalley, H., Willinger, D., Winter, A., Wittfeld, K., Yang, T. T., Yoncheva, Y., Zijlmans, J. L., Hoogman, M., Franke, B., van Rooij, D., Buitelaar, J., Ching, C. R., Andreassen, O. A., Pozzi, E., Veltman, D., Schmaal, L., van Erp, T. G., Turner, J., Castellanos, F. X., Pausova, Z., Thompson, P., Paus, T. 2022

  Abstract

  Morphology of the human cerebral cortex differs across psychiatric disorders, with neurobiology and developmental origins mostly undetermined. Deviations in the tangential growth of the cerebral cortex during pre/perinatal periods may be reflected in individual variations in cortical surface area later in life.Interregional profiles of group differences in surface area between cases and controls were generated using T1-weighted magnetic resonance imaging from 27,359 individuals including those with attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depressive disorder, schizophrenia, and high general psychopathology (through the Child Behavior Checklist). Similarity of interregional profiles of group differences in surface area and prenatal cell-specific gene expression was assessed.Across the 11 cortical regions, group differences in cortical area for attention-deficit/hyperactivity disorder, schizophrenia, and Child Behavior Checklist were dominant in multimodal association cortices. The same interregional profiles were also associated with interregional profiles of (prenatal) gene expression specific to proliferative cells, namely radial glia and intermediate progenitor cells (greater expression, larger difference), as well as differentiated cells, namely excitatory neurons and endothelial and mural cells (greater expression, smaller difference). Finally, these cell types were implicated in known pre/perinatal risk factors for psychosis. Genes coexpressed with radial glia were enriched with genes implicated in congenital abnormalities, birth weight, hypoxia, and starvation. Genes coexpressed with endothelial and mural genes were enriched with genes associated with maternal hypertension and preterm birth.Our findings support a neurodevelopmental model of vulnerability to mental illness whereby prenatal risk factors acting through cell-specific processes lead to deviations from typical brain development during pregnancy.

  View details for DOI 10.1016/j.biopsych.2022.02.959

  View details for PubMedID 35489875

• Sex-specific vulnerability to depressive symptoms across adolescence and during the COVID-19 pandemic: The role of the cingulum bundle. JCPP advances Chahal, R., Ho, T. C., Miller, J. G., Borchers, L. R., Gotlib, I. H. 2022; 2 (1): e12061

  Abstract

  Background: Females are at higher risk for developing depression during adolescence than are males, particularly during exposure to stressors like the COVID-19 pandemic. Examining structural connections between brain regions involved in executive functioning may advance our understanding of sex biases in stress and depression. Here, we examined the role of the cingulum bundle in differentiating trajectories of depressive symptoms in males and females across adolescence and during the pandemic.Methods: In a longitudinal study of 214 youth (121 females; ages 9-13years at baseline), we examined whether fixel-based properties of the cingulum bundle at baseline predict changes in females' and males' severity of depressive symptoms across four timepoints (4-7years) in adolescence, including during the COVID-19 pandemic. We also tested whether cingulum properties predict self-reported resilience and stress during the pandemic.Results: Females had lower fiber density and cross-section (FDC) of the cingulum than did males, a neural pattern that predicted greater increases in depressive symptoms, lower resilience, and higher stress during the COVID-19 pandemic. Cingulum morphometry predicted changes in depressive trajectories in females, but not in males; specifically, females with lower FDC had significant increases in symptoms throughout adolescence, whereas females with higher cingulum FDC did not. Conversely, males had low, stable depressive symptoms throughout adolescence and higher resilience and lower stress during the pandemic compared to females. Higher cingulum FDC predicted higher resilience and lower stress in both sexes.Conclusions: In adults, the cingulum has been implicated in sex differences in stress reactivity. We show that in adolescents, the cingulum reflects sex differences in reports of stress and resilience that might contribute to the increased risk of stress-related mood disorders in females. Adolescent females might benefit from cognitive interventions that strengthen the structural properties of the cingulum and increase their perceived resilience during periods of adversity and disruption.

  View details for DOI 10.1002/jcv2.12061

  View details for PubMedID 35572852

• Census tract ambient ozone predicts trajectories of depressive symptoms in adolescents. Developmental psychology Manczak, E. M., Miller, J. G., Gotlib, I. H. 2022; 58 (3): 485-492

  Abstract

  Exposure to ozone is a well-documented risk factor for negative physical health outcomes but has been considered less frequently in the context of socioemotional health. We examined whether levels of neighborhood ozone predicted trajectories of depressive symptoms over a four-year period in 213 adolescents (ages 9-13 years at baseline; 57% female; 53% of minority race/ethnicity). Participants self-reported depressive and other types of psychopathology symptoms up to 3 times, and their home addresses were used to compute ozone levels in their census tract. Possible confounding variables, including personal, family, and neighborhood characteristics, were also assessed. We found that higher ozone predicted steeper increases in depressive symptoms across adolescent development, a pattern that was not observed for other forms of psychopathology symptoms. These findings underscore the importance of considering ozone exposure in understanding trajectories of depressive symptoms across adolescence. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

  View details for DOI 10.1037/dev0001310

  View details for PubMedID 35286107

• Cellular Aging and Stress in Pregnant and Non-Pregnant People During the COVID-19 Pandemic Panelli, D., Diwan, M., Cruz, G. I., Leonard, S. A., Chueh, J., Gotlib, I. H., Bianco, K. SPRINGER HEIDELBERG. 2022: 191

  View details for Web of Science ID 000762765300376

• Leukocyte Telomere Length in the First Trimester of Pregnancy and its Association with Perinatal Outcomes Panelli, D., Diwan, M., Cruz, G. I., Leonard, S. A., Chueh, J., Gotlib, I. H., Bianco, K. SPRINGER HEIDELBERG. 2022: 155

  View details for Web of Science ID 000762765300282

• Hair cortisol concentration across the peripartum period: Documenting changes and associations with depressive symptoms and recent adversity. Comprehensive psychoneuroendocrinology King, L. S., Humphreys, K. L., Cole, D. A., Gotlib, I. H. 2022; 9: 100102

  Abstract

  Women experience dramatic physiological changes during pregnancy, including changes in the production of the "stress hormone," cortisol. Evidence has been mixed regarding whether hair cortisol concentration (HCC) can be used to accurately capture the trajectory of cortisol during this period and whether factors related to psychosocial stress are related to HCC in pregnant and postpartum women. In the current study, we collected hair samples from 85 individuals during the peripartum period (with collection occasions in pregnancy [12-37 weeks], at 3-8 weeks postpartum, and at 5-8 months postpartum) from which we derived 783 monthly observations of HCC. In addition, at each assessment individuals reported their current depressive symptoms and experiences of recent psychosocial adversity. Using piecewise mixed effects modeling, we identified significant increases in HCC across pregnancy (approximately a 2-fold rise) followed by significant decreases in HCC postpartum. Beyond these effects, however, there was substantial within-individual variability in HCC. Disaggregating between- from within-individual associations of depressive symptoms and adversity with HCC, we found that within-individual fluctuations in adversity were positively coupled with levels of HCC. Overall, the current findings suggest that measurement of cortisol in human hair captures its trajectory from conception through six months postpartum, including prenatal increases and gradual recovery of typical levels following childbirth. In addition to the overall severity of psychosocial adversity, change in women's experiences of adversity during the peripartum period merit attention.

  View details for DOI 10.1016/j.cpnec.2021.100102

  View details for PubMedID 35755930

  View details for PubMedCentralID PMC9216355

• An exploration of dimensions of early adversity and the development of functional brain network connectivity during adolescence: Implications for trajectories of internalizing symptoms. Development and psychopathology Chahal, R., Miller, J. G., Yuan, J. P., Buthmann, J. L., Gotlib, I. H. 1800: 1-15

  Abstract

  Different dimensions of adversity may affect mental health through distinct neurobiological mechanisms, though current supporting evidence consists largely of cross-sectional associations between threat or deprivation and fronto-limbic circuitry. In this exploratory three-wave longitudinal study spanning ages 9-19 years, we examined the associations between experiences of unpredictability, threat, and deprivation with the development of functional connectivity within and between three brain networks implicated in psychopathology: the salience (SAL), default mode (DMN), and fronto-parietal (FPN) networks, and tested whether network trajectories moderated associations between adversity and changes in internalizing symptoms. Connectivity decreased with age on average; these changes differed by dimension of adversity. Whereas family-level deprivation was associated with lower initial levels and more stability across most networks, unpredictability was associated with stability only in SAL connectivity, and threat was associated with stability in FPN and DMN-SAL connectivity. In youth exposed to higher levels of any adversity, lower initial levels and more stability in connectivity were related to smaller increases in internalizing symptoms. Our findings suggest that whereas deprivation is associated with widespread neurodevelopmental differences in cognitive and emotion processing networks, unpredictability is related selectively to salience detection circuitry. Studies with wider developmental windows should examine whether these neurodevelopmental alterations are adaptive or serve to maintain internalizing symptoms.

  View details for DOI 10.1017/S0954579421001814

  View details for PubMedID 35094729

• Behavioral coping phenotypes and associated psychosocial outcomes of pregnant and postpartum women during the COVID-19 pandemic. Scientific reports Werchan, D. M., Hendrix, C. L., Ablow, J. C., Amstadter, A. B., Austin, A. C., Babineau, V., Anne Bogat, G., Cioffredi, L., Conradt, E., Crowell, S. E., Dumitriu, D., Fifer, W., Firestein, M. R., Gao, W., Gotlib, I. H., Graham, A. M., Gregory, K. D., Gustafsson, H. C., Havens, K. L., Howell, B. R., Humphreys, K. L., King, L. S., Kinser, P. A., Krans, E. E., Lenniger, C., Levendosky, A. A., Lonstein, J. S., Marcus, R., Monk, C., Moyer, S., Muzik, M., Nuttall, A. K., Potter, A. S., Salisbury, A., Shuffrey, L. C., Smith, B. A., Smith, L., Sullivan, E. L., Zhou, J., Thomason, M. E., Brito, N. H. 1800; 12 (1): 1209

  Abstract

  The impact of COVID-19-related stress on perinatal women is of heightened public health concern given the established intergenerational impact of maternal stress-exposure on infants and fetuses. There is urgent need to characterize the coping styles associated with adverse psychosocial outcomes in perinatal women during the COVID-19 pandemic to help mitigate the potential for lasting sequelae on both mothers and infants. This study uses a data-driven approach to identify the patterns of behavioral coping strategies that associate with maternal psychosocial distress during the COVID-19 pandemic in a large multicenter sample of pregnant women (N=2876) and postpartum women (N=1536). Data was collected from 9 states across the United States from March to October 2020. Women reported behaviors they were engaging in to manage pandemic-related stress, symptoms of depression, anxiety and global psychological distress, as well as changes in energy levels, sleep quality and stress levels. Using latent profile analysis, we identified four behavioral phenotypes of coping strategies. Critically, phenotypes with high levels of passive coping strategies (increased screen time, social media, and intake of comfort foods) were associated with elevated symptoms of depression, anxiety, and global psychological distress, as well as worsening stress and energy levels, relative to other coping phenotypes. In contrast, phenotypes with high levels of active coping strategies (social support, and self-care) were associated with greater resiliency relative to other phenotypes. The identification of these widespread coping phenotypes reveals novel behavioral patterns associated with risk and resiliency to pandemic-related stress in perinatal women. These findings may contribute to early identification of women at risk for poor long-term outcomes and indicate malleable targets for interventions aimed at mitigating lasting sequelae on women and children during the COVID-19 pandemic.

  View details for DOI 10.1038/s41598-022-05299-4

  View details for PubMedID 35075202

• Revealing the impact of lifestyle stressors on the risk of adverse pregnancy outcomes with multitask machine learning. Frontiers in pediatrics Becker, M., Dai, J., Chang, A. L., Feyaerts, D., Stelzer, I. A., Zhang, M., Berson, E., Saarunya, G., De Francesco, D., Espinosa, C., Kim, Y., Maric, I., Mataraso, S., Payrovnaziri, S. N., Phongpreecha, T., Ravindra, N. G., Shome, S., Tan, Y., Thuraiappah, M., Xue, L., Mayo, J. A., Quaintance, C. C., Laborde, A., King, L. S., Dhabhar, F. S., Gotlib, I. H., Wong, R. J., Angst, M. S., Shaw, G. M., Stevenson, D. K., Gaudilliere, B., Aghaeepour, N. 2022; 10: 933266

  Abstract

  Psychosocial and stress-related factors (PSFs), defined as internal or external stimuli that induce biological changes, are potentially modifiable factors and accessible targets for interventions that are associated with adverse pregnancy outcomes (APOs). Although individual APOs have been shown to be connected to PSFs, they are biologically interconnected, relatively infrequent, and therefore challenging to model. In this context, multi-task machine learning (MML) is an ideal tool for exploring the interconnectedness of APOs on the one hand and building on joint combinatorial outcomes to increase predictive power on the other hand. Additionally, by integrating single cell immunological profiling of underlying biological processes, the effects of stress-based therapeutics may be measurable, facilitating the development of precision medicine approaches.Objectives: The primary objectives were to jointly model multiple APOs and their connection to stress early in pregnancy, and to explore the underlying biology to guide development of accessible and measurable interventions.Materials and Methods: In a prospective cohort study, PSFs were assessed during the first trimester with an extensive self-filled questionnaire for 200 women. We used MML to simultaneously model, and predict APOs (severe preeclampsia, superimposed preeclampsia, gestational diabetes and early gestational age) as well as several risk factors (BMI, diabetes, hypertension) for these patients based on PSFs. Strongly interrelated stressors were categorized to identify potential therapeutic targets. Furthermore, for a subset of 14 women, we modeled the connection of PSFs to the maternal immune system to APOs by building corresponding ML models based on an extensive single cell immune dataset generated by mass cytometry time of flight (CyTOF).Results: Jointly modeling APOs in a MML setting significantly increased modeling capabilities and yielded a highly predictive integrated model of APOs underscoring their interconnectedness. Most APOs were associated with mental health, life stress, and perceived health risks. Biologically, stressors were associated with specific immune characteristics revolving around CD4/CD8 T cells. Immune characteristics predicted based on stress were in turn found to be associated with APOs.Conclusions: Elucidating connections among stress, multiple APOs simultaneously, and immune characteristics has the potential to facilitate the implementation of ML-based, individualized, integrative models of pregnancy in clinical decision making. The modifiable nature of stressors may enable the development of accessible interventions, with success tracked through immune characteristics.

  View details for DOI 10.3389/fped.2022.933266

  View details for PubMedID 36582513

• Early Life Stress and Neurodevelopment in Adolescence: Implications for Risk and Adaptation. Current topics in behavioral neurosciences Miller, J. G., Chahal, R., Gotlib, I. H. 2022

  Abstract

  An alarming high proportion of youth experience at least one kind of stressor in childhood and/or adolescence. Exposure to early life stress is associated with increased risk for psychopathology, accelerated biological aging, and poor physical health; however, it is important to recognize that not all youth who experience such stress go on to develop difficulties. In fact, resilience, or positive adaptation in the face of adversity, is relatively common. Individual differences in vulnerability or resilience to the effects of early stress may be represented in the brain as specific patterns, profiles, or signatures of neural activation, structure, and connectivity (i.e., neurophenotypes). Whereas neurophenotypes of risk that reflect the deleterious effects of early stress on the developing brain are likely to exacerbate negative outcomes in youth, neurophenotypes of resilience may reduce the risk of experiencing these negative outcomes and instead promote positive functioning. In this chapter we describe our perspective concerning the neurobiological mechanisms and moderators of risk and resilience in adolescence following early life stress and integrate our own work into this framework. We present findings suggesting that exposure to stress in childhood and adolescence is associated with functional and structural alterations in neurobiological systems that are important for social-affective processing and for cognitive control. While some of these neurobiological alterations increase risk for psychopathology, they may also help to limit adolescents' sensitivity to subsequent negative experiences. We also discuss person-centered strategies that we believe can advance our understanding of risk and resilience to early stress in adolescents. Finally, we describe ways in which the field can broaden its focus to include a consideration of other types of environmental factors, such as environmental pollutants, in affecting both risk and resilience to stress-related health difficulties in youth.

  View details for DOI 10.1007/7854_2022_302

  View details for PubMedID 35290658

• Maternal stress and its consequences - biological strain. American journal of perinatology Stevenson, D. K., Gotlib, I. H., Buthmann, J. L., Maric, I., Aghaeepour, N., Gaudilliere, B., Angst, M. S., Darmstadt, G. L., Druzin, M. L., Wong, R. J., Shaw, G. M., Katz, M. 2022

  Abstract

  Understanding the role of stress in pregnancy and its consequences is important, particularly given documented associations between maternal stress and preterm birth and other pathologic outcomes. Physical and psychological stressors can elicit the same biological responses, known as biological strain. Chronic stressors, like poverty and racism (race-based discriminatory treatment), may create a legacy or trajectory of biological strain that no amount of coping can relieve in the absence of larger-scale socio-behavioral or societal changes. An integrative approach that takes into consideration simultaneously social and biological determinants of stress may provide the best insights into risk for preterm birth. The most successful computational approaches and the most predictive machine-learning models are likely to be those that combine information about the stressors and the biological strain (for example, as measured by different omics) experienced during pregnancy.

  View details for DOI 10.1055/a-1798-1602

  View details for PubMedID 35292943

• Inflammatory cytokines and callosal white matter microstructure in adolescents. Brain, behavior, and immunity Ho, T. C., Kulla, A., Teresi, G. I., Sisk, L. M., Rosenberg-Hasson, Y., Maecker, H. T., Gotlib, I. H. 1800

  Abstract

  Adolescent depression is characterized by heightened inflammation and altered connectivity of fronto-cingulate-limbic tracts, including the genu of the corpus callosum (CCG) and the uncinate fasciculus (UF). No studies, however, have yet examined the association between inflammation, measured by peripheral levels of cytokines, and white matter connectivity of fronto-cingulate-limbic tracts in adolescents. Here, 56 depressed adolescents (32 females, 3 non-binary; 16.23±1.28 years) and 19 controls (10 females; 15.72±1.17 years) completed a diffusion-weighted MRI scan at 3 Tesla. We conducted deterministic tractography to segment bilateral corpus callosum (genu and splenium) and UF and computed mean fractional anisotropy (FA) in each tract. A subset of participants (43 depressed and 17 healthy controls) also provided dried blood spot samples from which we assayed interleukin 6 (IL-6) and tumor necrosis alpha (TNF-ɑ) using a Luminex multiplex array. Depressed participants did not differ from controls in FA of the corpus callosum or UF (all FDR-corrected ps>0.056) but exhibited higher levels of inflammation than did controls (IL-6: beta=0.91, FDR-corrected p=0.006; TNF-alpha: beta=0.76, FDR-corrected p=0.006). Although diagnostic group did not moderate the associations between inflammatory cytokines and FA in the CCG and UF, across both groups, greater peripheral inflammation was associated with lower FA in the CCG (IL-6: beta=-0.38; FDR-corrected p=0.044; TNF-ɑ: beta=-0.41, FDR-corrected p=0.044). This study is the first to examine associations between peripheral inflammation and white matter microstructure of fronto-cingulate-limbic tracts in depressed and nondepressed adolescents. Future mechanistic studies are needed to confirm our findings; nevertheless, our results suggest that heightened inflammation is an important component of neurophenotypes that are relevant to adolescent depression.

  View details for DOI 10.1016/j.bbi.2021.12.003

  View details for PubMedID 34896593

• Testing a Developmental Model of Positive Parenting, Amygdala-Subgenual Anterior Cingulate Cortex Connectivity, and Depressive Symptoms in Adolescents Before and During the COVID-19 Pandemic. Biological psychiatry global open science Miller, J. G., Ho, T. C., Kirshenbaum, J. S., Chahal, R., Gifuni, A. J., Gotlib, I. H. 2021; 1 (4): 291-299

  Abstract

  Neurobiological measures may inform our understanding of individual differences in adolescents' general risk for and resilience to depressive symptoms, including during the COVID-19 pandemic. We tested a developmental model linking variation in amygdala-subgenual anterior cingulate cortex (sgACC) resting-state connectivity to perceived parenting experiences earlier in adolescence, to concurrent depressive symptoms before the pandemic, and to subsequent depressive symptoms during the pandemic.We used data from a longitudinal study that included three waves (N = 214 adolescents; ages 9-15 years at time 1 [T1], 11-17 years at T2, and 12-19 years during the pandemic at T3). We assessed positive parenting (warm and supportive) (T1), depressive symptoms (T1 to T3), and functional connectivity between the sgACC and basolateral (BLA) and centromedial amygdala (T1 and T2). We modeled associations among earlier positive parenting, amygdala-sgACC connectivity, and depressive symptoms before and during the pandemic.Less positive parenting at T1 was associated prospectively with stronger BLA-sgACC connectivity at T2 (β = -0.22) over and above the effect of BLA-sgACC connectivity at T1. Stronger BLA-sgACC connectivity, in turn, was associated with heightened depressive symptoms, both before the pandemic (r = 0.21) and during the pandemic (β = 0.19; independent of the effect of pre-pandemic symptoms).Adolescents who experience less positive parenting may develop a pattern of BLA-sgACC connectivity that increases their risk for mental health problems. BLA-sgACC connectivity may be associated with depressive symptoms in general, including during periods of heightened risk for adolescents, such as the pandemic.

  View details for DOI 10.1016/j.bpsgos.2021.07.005

  View details for PubMedID 36325504

  View details for PubMedCentralID PMC9616303

• Effects of COVID-19-related life changes on mental health in Syrian refugees in Turkey. BJPsych open Bernardi, L., Gotlib, I. H., Zihnioglu, O. 2021; 7 (6): e182

  Abstract

  Background: Mental disorders are currently the greatest global health burden. The coronavirus diseases 2019 (COVID-19) pandemic is having an adverse impact on people's mental health, particularly in vulnerable populations, such as refugees.Aims: The present study was designed to examine the association between COVID-19 and changes in mental health in Syrian refugees in Turkey.Method: We conducted a two-wave panel survey of a representative sample of 302 of the estimated 500 000 Syrian refugees (ages 18 and older) living under humanitarian support in Istanbul (first wave between 9 and 15 July 2020 and the follow-up between 11 and 14 September 2020). We administered seven items from the CoRonavIruS Health Impact Survey in addition to one-context specific item about life changes because of COVID-19, and measures of depression (10-item Center for Epidemiologic Study Depression Scale, CESD-10), anxiety (6-item State-Trait Anxiety Inventory, STAI-6) and perceived stress (Perceived Stress Scale, PSS-4).Results: A factor analysis yielded three COVID-19 factors, labelled 'social relationships', 'stress' and 'hope.' We conducted a series of cross-lag panel analyses to test associations between the COVID-19 factors and mental health. We found associations between all COVID-19 factors and CESD-10, between COVID-19 'stress' and STAI-6, and between COVID-19 'stress' and COVID-19 'hope' and PSS-4.Conclusions: Our measures of life changes because of the COVID-19 pandemic are associated with changes in the mental health of Syrian refugees living in Istanbul. It is therefore important that they are provided with services to reduce what may be particularly debilitating consequences of COVID-19.

  View details for DOI 10.1192/bjo.2021.1009

  View details for PubMedID 34659792

• Convergence, preliminary findings and future directions across the four human connectome projects investigating mood and anxiety disorders. NeuroImage Tozzi, L., Anene, E. T., Gotlib, I. H., Wintermark, M., Kerr, A. B., Wu, H., Seok, D., Narr, K. L., Sheline, Y. I., Whitfield-Gabrieli, S., Williams, L. M. 2021: 118694

  Abstract

  In this paper we provide an overview of the rationale, methods, and preliminary results of the four Connectome Studies Related to Human Disease investigating mood and anxiety disorders. The first study, "Dimensional connectomics of anxious misery" (HCP-DAM), characterizes brain-symptom relations of a transdiagnostic sample of anxious misery disorders. The second study, "Human connectome Project for disordered emotional states" (HCP-DES), tests a hypothesis-driven model of brain circuit dysfunction in a sample of untreated young adults with symptoms of depression and anxiety. The third study, "Perturbation of the treatment resistant depression connectome by fast-acting therapies" (HCP-MDD), quantifies alterations of the structural and functional connectome as a result of three fast-acting interventions: electroconvulsive therapy, serial ketamine therapy, and total sleep deprivation. Finally, the fourth study, "Connectomes related to anxiety and depression in adolescents" (HCP-ADA), investigates developmental trajectories of subtypes of anxiety and depression in adolescence. The four projects use comparable and standardized Human Connectome Project magnetic resonance imaging (MRI) protocols, including structural MRI, diffusion-weighted MRI, and both task and resting state functional MRI. All four projects also conducted comprehensive and convergent clinical and neuropsychological assessments, including (but not limited to) demographic information, clinical diagnoses, symptoms of mood and anxiety disorders, negative and positive affect, cognitive function, and exposure to early life stress. The first round of analyses conducted in the four projects offered novel methods to investigate relations between functional connectomes and self-reports in large datasets, identified new functional correlates of symptoms of mood and anxiety disorders, characterized the trajectory of connectome-symptom profiles over time, and quantified the impact of novel treatments on aberrant connectivity. Taken together, the data obtained and reported by the four Connectome Studies Related to Human Disease investigating mood and anxiety disorders describe a rich constellation of convergent biological, clinical, and behavioral phenotypes that span the peak ages for the onset of emotional disorders. These data are being prepared for open sharing with the scientific community following screens for quality by the Connectome Coordinating Facility (CCF). The CCF also plans to release data from all projects that have been pre-processed using identical state-of-the-art pipelines. The resultant dataset will give researchers the opportunity to pool complementary data across the four projects to study circuit dysfunctions that may underlie mood and anxiety disorders, to map cohesive relations among circuits and symptoms, and to probe how these relations change as a function of age and acute interventions. This large and combined dataset may also be ideal for using data-driven analytic approaches to inform neurobiological targets for future clinical trials and interventions focused on clinical or behavioral outcomes.

  View details for DOI 10.1016/j.neuroimage.2021.118694

  View details for PubMedID 34732328

• Altered resting-state functional connectome in major depressive disorder: a mega-analysis from the PsyMRI consortium. Translational psychiatry Javaheripour, N., Li, M., Chand, T., Krug, A., Kircher, T., Dannlowski, U., Nenadic, I., Hamilton, J. P., Sacchet, M. D., Gotlib, I. H., Walter, H., Frodl, T., Grimm, S., Harrison, B. J., Wolf, C. R., Olbrich, S., van Wingen, G., Pezawas, L., Parker, G., Hyett, M. P., Samann, P. G., Hahn, T., Steinstrater, O., Jansen, A., Yuksel, D., Kampe, R., Davey, C. G., Meyer, B., Bartova, L., Croy, I., Walter, M., Wagner, G. 2021; 11 (1): 511

  Abstract

  Major depressive disorder (MDD) is associated with abnormal neural circuitry. It can be measured by assessing functional connectivity (FC) at resting-state functional MRI, that may help identifying neural markers of MDD and provide further efficient diagnosis and monitor treatment outcomes. The main aim of the present study is to investigate, in an unbiased way, functional alterations in patients with MDD using a large multi-center dataset from the PsyMRI consortium including 1546 participants from 19 centers ( www.psymri.com ). After applying strict exclusion criteria, the final sample consisted of 606 MDD patients (age: 35.8±11.9y.o.; females: 60.7%) and 476 healthy participants (age: 33.3±11.0y.o.; females: 56.7%). We found significant relative hypoconnectivity within somatosensory motor (SMN), salience (SN) networks and between SMN, SN, dorsal attention (DAN), and visual (VN) networks in MDD patients. No significant differences were detected within the default mode (DMN) and frontoparietal networks (FPN). In addition, alterations in network organization were observed in terms of significantly lower network segregation of SMN in MDD patients. Although medicated patients showed significantly lower FC within DMN, FPN, and SN than unmedicated patients, there were no differences between medicated and unmedicated groups in terms of network organization in SMN. We conclude that the network organization of cortical networks, involved in processing of sensory information, might be a more stable neuroimaging marker for MDD than previously assumed alterations in higher-order neural networks like DMN and FPN.

  View details for DOI 10.1038/s41398-021-01619-w

  View details for PubMedID 34620830

• Correlates and predictors of the severity of suicidal ideation in adolescence: an examination of brain connectomics and psychosocial characteristics. Journal of child psychology and psychiatry, and allied disciplines Kirshenbaum, J. S., Chahal, R., Ho, T. C., King, L. S., Gifuni, A. J., Mastrovito, D., Coury, S. M., Weisenburger, R. L., Gotlib, I. H. 2021

  Abstract

  BACKGROUND: Suicidal ideation (SI) typically emerges during adolescence but is challenging to predict. Given the potentially lethal consequences of SI, it is important to identify neurobiological and psychosocial variables explaining the severity of SI in adolescents.METHODS: In 106 participants (59 female) recruited from the community, we assessed psychosocial characteristics and obtained resting-state fMRI data in early adolescence (baseline: aged 9-13years). Across 250 brain regions, we assessed local graph theory-based properties of interconnectedness: local efficiency, eigenvector centrality, nodal degree, within-module z-score, and participation coefficient. Four years later (follow-up: ages 13-19years), participants self-reported their SI severity. We used least absolute shrinkage and selection operator (LASSO) regressions to identify a linear combination of psychosocial and brain-based variables that best explain the severity of SI symptoms at follow-up. Nested-cross-validation yielded model performance statistics for all LASSO models.RESULTS: A combination of psychosocial and brain-based variables explained subsequent severity of SI (R2 =.55); the strongest was internalizing and externalizing symptom severity at follow-up. Follow-up LASSO regressions of psychosocial-only and brain-based-only variables indicated that psychosocial-only variables explained 55% of the variance in SI severity; in contrast, brain-based-only variables performed worse than the null model.CONCLUSIONS: A linear combination of baseline and follow-up psychosocial variables best explained the severity of SI. Follow-up analyses indicated that graph theory resting-state metrics did not increase the prediction of the severity of SI in adolescents. Attending to internalizing and externalizing symptoms is important in early adolescence; resting-state connectivity properties other than local graph theory metrics might yield a stronger prediction of the severity of SI.

  View details for DOI 10.1111/jcpp.13512

  View details for PubMedID 34448494

• White Matter Microstructural Properties of the Cerebellar Peduncles Predict Change in Symptoms of Psychopathology in Adolescent Girls. Cerebellum (London, England) Borchers, L. R., Bruckert, L., Chahal, R., Mastrovito, D., Ho, T. C., Gotlib, I. H. 2021

  Abstract

  Internalizing symptoms typically emerge in adolescence and are more prevalent in females than in males; in contrast, externalizing symptoms typically emerge in childhood and are more commonly observed in males. Previous research has implicated aspects of white matter organization, including fractional anisotropy (FA), of cerebral tracts in both internalizing and externalizing symptoms. Although the cerebellum has been posited to integrate limbic and cortical regions, its role in psychopathology is not well understood. In this longitudinal study, we investigated whether FA of the superior (SCP), middle (MCP), and inferior cerebellar peduncles (ICP) predict change in symptoms and whether sex moderates this association. One hundred eleven adolescents completed the Youth Self-Report, assessing symptoms at baseline (ages 9-13years) and again 2years later. Participants also underwent diffusion-weighted imaging at baseline. We used deterministic tractography to segment and compute mean FA of the cerebellar peduncles. Lower FA of the right SCP at baseline predicted increases in internalizing symptoms in females only. Lower FA in the right SCP and ICP also predicted increases in externalizing symptoms in females, but these associations did not survive multiple comparison correction. There was no association between FA of the cerebellar peduncles and change in symptoms in males or between MCP FA and symptom changes in males or females. Organizational properties of the SCP may be a sex-specific marker of internalizing symptom changes in adolescence. The cerebellar peduncles should be explored further in future studies to elucidate sex differences in symptoms.

  View details for DOI 10.1007/s12311-021-01307-x

  View details for PubMedID 34309819

• Sex differences in myelin content of white matter tracts in adolescents with depression. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology Ho, T. C., Sisk, L. M., Kulla, A., Teresi, G. I., Hansen, M. M., Wu, H., Gotlib, I. H. 2021

  Abstract

  Depression is a chronic and debilitating condition that often emerges during adolescence, a period of significant brain maturation. Few studies, however, have examined how mechanisms of neuroplasticity, including myelination, are affected by adolescent-onset depression. Here, we used multimodal MR imaging to characterize myelin, indexed by R1, in white matter tracts previously associated with depression and compare 48 adolescents with lifetime depression (45 with current depression, 3 remitted) and 35 healthy controls in R1. Compared to healthy controls, R1 was higher in adolescents with lifetime depression in the uncinate fasciculus and corpus callosum genu (all betas>0.42; all ps<0.037). Sex significantly moderated the association between depression and R1 in the left uncinate fasciculus and corpus callosum genu (all betas>0.86; all ps<0.02), such that depressed female adolescents had significantly higher R1 in these tracts than did healthy female adolescents (all betas>0.82; all ps<0.0012). In contrast, depressed and non-depressed male adolescents did not differ in R1 in these tracts (all ps>0.32). While fractional anisotropy (FA), a commonly examined measure of white matter organization based on diffusion-weighted MRI, in the left uncinate was positively associated with lifetime depression in our sample (beta=0.56; p=0.016), we found no evidence of sex-specific effects of depression in FA. Our results suggest that R1 is more sensitive to sex-specific effects of depression than FA, particularly in female adolescents. Given evidence that myelin inhibits synapse formation and reduces brain plasticity, our findings implicate experience-driven regional myelination as a mechanism underlying depression during periods of significant neural maturation such as adolescence.

  View details for DOI 10.1038/s41386-021-01078-3

  View details for PubMedID 34215842

• Coping Strategies, Neural Structure, and Depression and Anxiety During the COVID-19 Pandemic: A Longitudinal Study in a Naturalistic Sample Spanning Clinical Diagnoses and Subclinical Symptoms. Biological psychiatry global open science Holt-Gosselin, B., Tozzi, L., Ramirez, C. A., Gotlib, I. H., Williams, L. M. 2021

  Abstract

  Background: Although the COVID-19 pandemic has been shown to worsen anxiety and depression symptoms, we do not understand which behavioral and neural factors may mitigate this impact. To address this gap, we assessed whether adaptive and maladaptive coping strategies affect symptom trajectory during the pandemic. We also examined whether pre-pandemic integrity of brain regions implicated in depression and anxiety affect pandemic symptoms.Methods: In a naturalistic sample of 169 adults (66.9% female; age 19-74 years) spanning psychiatric diagnoses and subclinical symptoms, we assessed anhedonia, tension, and anxious arousal symptoms using validated components (21-item Depression, Anxiety, and Stress Scale), coping strategies (Brief-Coping Orientation to Problems Experienced), and gray matter volume (amygdala) and cortical thickness (hippocampus, insula, anterior cingulate cortex) from magnetic resonance imaging T1-weighted scans. We conducted general linear mixed-effects models to test preregistered hypotheses that 1) maladaptive coping pre-pandemic and 2) lower structural integrity pre-pandemic would predict more severe pandemic symptoms; and 3) coping would interact with neural structure to predict pandemic symptoms.Results: Greater use of maladaptive coping strategies was associated with more severe anxious arousal symptoms during the pandemic (p= .011, false discovery rate-corrected p [p FDR]= .035), specifically less self-distraction (p= .014, p FDR= .042) and greater self-blame (p= .002, p FDR= .012). Reduced insula thickness pre-pandemic predicted more severe anxious arousal symptoms (p= .001, p FDR= .027). Self-distraction interacted with amygdala volume to predict anhedonia symptoms (p= .005, p FDR= .020).Conclusions: Maladaptive coping strategies and structural variation in brain regions may influence clinical symptoms during a prolonged stressful event (e.g., COVID-19 pandemic). Future studies that identify behavioral and neural factors implicated in responses to global health crises are warranted for fostering resilience.

  View details for DOI 10.1016/j.bpsgos.2021.06.007

  View details for PubMedID 34604834

• Correction: Brain structural abnormalities in obesity: relation to age, genetic risk, and common psychiatric disorders. Molecular psychiatry Opel, N., Thalamuthu, A., Milaneschi, Y., Grotegerd, D., Flint, C., Leenings, R., Goltermann, J., Richter, M., Hahn, T., Woditsch, G., Berger, K., Hermesdorf, M., McIntosh, A., Whalley, H. C., Harris, M. A., MacMaster, F. P., Walter, H., Veer, I. M., Frodl, T., Carballedo, A., Krug, A., Nenadic, I., Kircher, T., Aleman, A., Groenewold, N. A., Stein, D. J., Soares, J. C., Zunta-Soares, G. B., Mwangi, B., Wu, M., Walter, M., Li, M., Harrison, B. J., Davey, C. G., Cullen, K. R., Klimes-Dougan, B., Mueller, B. A., Samann, P. G., Penninx, B., Nawijn, L., Veltman, D. J., Aftanas, L., Brak, I. V., Filimonova, E. A., Osipov, E. A., Reneman, L., Schrantee, A., Grabe, H. J., Van der Auwera, S., Wittfeld, K., Hosten, N., Volzke, H., Sim, K., Gotlib, I. H., Sacchet, M. D., Lagopoulos, J., Hatton, S. N., Hickie, I., Pozzi, E., Thompson, P. M., Jahanshad, N., Schmaal, L., Baune, B. T., Dannlowski, U. 2021

  View details for DOI 10.1038/s41380-021-01191-1

  View details for PubMedID 34158622

• Psychobiological risk factors for suicidal thoughts and behaviors in adolescence: a consideration of the role of puberty. Molecular psychiatry Ho, T. C., Gifuni, A. J., Gotlib, I. H. 2021

  Abstract

  Suicide is the second leading cause of death among adolescents. While clinicians and researchers have begun to recognize the importance of considering multidimensional factors in understanding risk for suicidal thoughts and behaviors (STBs) during this developmental period, the role of puberty has been largely ignored. In this review, we contend that the hormonal events that occur during puberty have significant effects on the organization and development of brain systems implicated in the regulation of social stressors, including amygdala, hippocampus, striatum, medial prefrontal cortex, orbitofrontal cortex, and anterior cingulate cortex. Guided by previous experimental work in adults, we also propose that the influence of pubertal hormones and social stressors on neural systems related to risk for STBs is especially critical to consider in adolescents with a neurobiological sensitivity to hormonal changes. Furthermore, facets of the pubertal transition, such as pubertal timing, warrant deeper investigation and may help us gain a more comprehensive understanding of sex differences in the neurobiological and psychosocial mechanisms underlying adolescent STBs. Ultimately, advancing our understanding of the pubertal processes that contribute to suicide risk will improve early detection and facilitate the development of more effective, sex-specific, psychiatric interventions for adolescents.

  View details for DOI 10.1038/s41380-021-01171-5

  View details for PubMedID 34117365

• Brain cortical and subcortical morphology in adolescents with depression and a history of suicide attempt. Journal of psychiatry & neuroscience : JPN Gifuni, A. J., Chakravarty, M. M., Lepage, M., Ho, T. C., Geoffroy, M., Lacourse, E., Gotlib, I. H., Turecki, G., Renaud, J., Jollant, F. 2021; 46 (3): E347–E357

  Abstract

  Background: Suicidal behaviours are a major source of mortality and morbidity among adolescents. Given the maturational changes that occur in cortical and subcortical structures during adolescence, we tested whether atypical brain structural measurements were associated with a history of suicide attempt.Methods: We assessed 3 groups of adolescents (n = 92; 79% female, mean age 15.9 years, range 11.6-18.1 years): patients with a depressive disorder and a history of suicide attempt (n = 28); patient controls, who had a depressive disorder but no history of suicide attempt (n = 34); and healthy controls (n = 30). We derived regional cortical thickness and surface area, and subcortical volumes, from T1-weighted anatomic MRI scans acquired at 3 T.Results: We found significant group differences in surface area in the prefrontal, temporal and parietal regions, as well as in the volume of several subcortical nuclei (pFDR ≤ 0.05), but not in cortical thickness. Post hoc analyses indicated that morphological alterations primarily differentiated patients with a history of suicide attempt from healthy controls, but not from patient controls. However, patients with a history of suicide attempt exhibited positive correlations between age and cortical thickness in the temporal cortices and right insula, and between age and right putamen volume (i.e., thicker regional cortex and larger subcortical volumes with age). These correlations were negative in both patient controls and healthy controls (i.e., thinner regional cortex and smaller subcortical volumes).Limitations: Sample sizes, cross-sectional findings and psychiatric heterogeneity were limitations of this study.Conclusion: Macroscopic structural differences in several brain regions differentiated adolescents with a history of suicide attempt from healthy controls, but not from patient controls. However, adolescents with a history of suicide attempt may present with atypical maturation of specific cortical and subcortical regions that might contribute to the risk of suicidal behaviour.

  View details for DOI 10.1503/jpn.200198

  View details for PubMedID 33961355

• Inflammatory Cytokines and Anterior Cingulate Cortex Glutamate in Adolescent Depression Segarra, J., Teresi, G., Gu, M., Spielman, D., Sacchet, M., Rosenberg-Hasson, Y., Maecker, H., Gotlib, I., Ho, T. ELSEVIER SCIENCE INC. 2021: S285

  View details for Web of Science ID 000645683800682

• Multi-Site Infant Brain Segmentation Algorithms: The iSeg-2019 Challenge IEEE TRANSACTIONS ON MEDICAL IMAGING Sun, Y., Gao, K., Wu, Z., Li, G., Zong, X., Lei, Z., Wei, Y., Ma, J., Yang, X., Feng, X., Li Zhao, Trung Le Phan, Shin, J., Zhong, T., Zhang, Y., Yu, L., Li, C., Basnet, R., Ahmad, M., Swamy, M. S., Ma, W., Dou, Q., Toan Duc Bui, Noguera, C., Landman, B., Gotlib, I. H., Humphreys, K. L., Shultz, S., Li, L., Niu, S., Lin, W., Jewells, V., Shen, D., Li, G., Li Wang 2021; 40 (5): 1363-1376

  Abstract

  To better understand early brain development in health and disorder, it is critical to accurately segment infant brain magnetic resonance (MR) images into white matter (WM), gray matter (GM), and cerebrospinal fluid (CSF). Deep learning-based methods have achieved state-of-the-art performance; h owever, one of the major limitations is that the learning-based methods may suffer from the multi-site issue, that is, the models trained on a dataset from one site may not be applicable to the datasets acquired from other sites with different imaging protocols/scanners. To promote methodological development in the community, the iSeg-2019 challenge (http://iseg2019.web.unc.edu) provides a set of 6-month infant subjects from multiple sites with different protocols/scanners for the participating methods. T raining/validation subjects are from UNC (MAP) and testing subjects are from UNC/UMN (BCP), Stanford University, and Emory University. By the time of writing, there are 30 automatic segmentation methods participated in the iSeg-2019. In this article, 8 top-ranked methods were reviewed by detailing their pipelines/implementations, presenting experimental results, and evaluating performance across different sites in terms of whole brain, regions of interest, and gyral landmark curves. We further pointed out their limitations and possible directions for addressing the multi-site issue. We find that multi-site consistency is still an open issue. We hope that the multi-site dataset in the iSeg-2019 and this review article will attract more researchers to address the challenging and critical multi-site issue in practice.

  View details for DOI 10.1109/TMI.2021.3055428

  View details for Web of Science ID 000645866500006

  View details for PubMedID 33507867

• Smartphone-Based Assessments of Negative Language Use, Central Executive Network Coherence, and Depression in Adolescents Teresi, G., Segarra, J., Kirshenbaum, J., Kahn, L., Allen, N., Gotlib, I., Ho, T. ELSEVIER SCIENCE INC. 2021: S247

  View details for Web of Science ID 000645683800591

• Sensitivity to Life Stress, Amygdala-Based Functional Connectivity, and Internalizing Symptoms in Adolescents Walker, J., Gifuni, A., Teresi, G., Weisenburger, R., Kirshenbaum, J., Ho, T., Gotlib, I. ELSEVIER SCIENCE INC. 2021: S363-S364

  View details for Web of Science ID 000645683800873

• Pregnancy during the pandemic: The impact of COVID-19-related stress on risk for prenatal depression. Psychological medicine King, L. S., Feddoes, D. E., Kirshenbaum, J. S., Humphreys, K. L., Gotlib, I. H. 2021: 1–32

  View details for DOI 10.1017/S003329172100132X

  View details for PubMedID 33781354

• Prefrontal cortex and amygdala anatomy in youth with persistent levels of harsh parenting practices and subclinical anxiety symptoms over time during childhood. Development and psychopathology Suffren, S., La Buissonniere-Ariza, V., Tucholka, A., Nassim, M., Seguin, J. R., Boivin, M., Kaur Singh, M., Foland-Ross, L. C., Lepore, F., Gotlib, I. H., Tremblay, R. E., Maheu, F. S. 2021: 1–12

  Abstract

  Childhood adversity and anxiety have been associated with increased risk for internalizing disorders later in life and with a range of brain structural abnormalities. However, few studies have examined the link between harsh parenting practices and brain anatomy, outside of severe maltreatment or psychopathology. Moreover, to our knowledge, there has been no research on parenting and subclinical anxiety symptoms which remain persistent over time during childhood (i.e., between 2.5 and 9 years old). Here, we examined data in 94 youth, divided into four cells based on their levels of coercive parenting (high / low) and of anxiety (high / low) between 2.5 and 9 years old. Anatomical images were analyzed using voxel-based morphometry (VBM) and FreeSurfer. Smaller gray matter volumes in the prefrontal cortex regions and in the amygdala were observed in youth with high versus low levels of harsh parenting over time. In addition, we observed significant interaction effects between parenting practices and subclinical anxiety symptoms in rostral anterior cingulate cortical thickness and in amygdala volume. These youth should be followed further in time to identify which youth will or will not go on to develop an anxiety disorder, and to understand factors associated with the development of sustained anxiety psychopathology.

  View details for DOI 10.1017/S0954579420001716

  View details for PubMedID 33745487

• Brain Correlates of Suicide Attempt in 18,925 Participants Across 18 International Cohorts. Biological psychiatry Campos, A. I., Thompson, P. M., Veltman, D. J., Pozzi, E., van Veltzen, L. S., Jahanshad, N., Adams, M. J., Baune, B. T., Berger, K., Brosch, K., Bulow, R., Connolly, C. G., Dannlowski, U., Davey, C. G., de Zubicaray, G. I., Dima, D., Erwin-Grabner, T., Evans, J. W., Fu, C. H., Gotlib, I. H., Goya-Maldonado, R., Grabe, H. J., Grotegerd, D., Harris, M. A., Harrison, B. J., Hatton, S. N., Hermesdorf, M., Hickie, I. B., Ho, T. C., Kircher, T., Krug, A., Lagopoulos, J., Lemke, H., McMahon, K., MacMaster, F. P., Martin, N. G., McIntosh, A. M., Medland, S. E., Meinert, S., Meller, T., Nenadic, I., Opel, N., Redlich, R., Reneman, L., Repple, J., Sacchet, M. D., Schmitt, S., Schrantee, A., Sim, K., Singh, A., Stein, F., Strike, L. T., van der Wee, N. J., van der Werff, S. J., Volzke, H., Waltemate, L., Whalley, H. C., Wittfeld, K., Wright, M. J., Yang, T. T., Zarate, C. A., Schmaal, L., Renteria, M. E., ENIGMA-MDD Working Group 2021

  Abstract

  BACKGROUND: Neuroimaging studies of suicidal behavior have so far been conducted in small samples, prone to biases and false-positive associations, yielding inconsistent results. The ENIGMA-MDD Working Group aims to address the issues of poor replicability and comparability by coordinating harmonized analyses across neuroimaging studies of major depressive disorder and related phenotypes, including suicidal behavior.METHODS: Here, we pooled data from 18 international cohorts with neuroimaging and clinical measurements in 18,925 participants (12,477 healthy control subjects and 6448 people with depression, of whom 694 had attempted suicide). We compared regional cortical thickness and surface area and measures of subcortical, lateral ventricular, and intracranial volumes between suicide attempters, clinical control subjects (nonattempters with depression), and healthy control subjects.RESULTS: We identified 25 regions of interest with statistically significant (false discovery rate < .05) differences between groups. Post hoc examinations identified neuroimaging markers associated with suicide attempt including smaller volumes of the left and right thalamus and the right pallidum and lower surface area of the left inferior parietal lobe.CONCLUSIONS: This study addresses the lack of replicability and consistency in several previously published neuroimaging studies of suicide attempt and further demonstrates the need for well-powered samples and collaborative efforts. Our results highlight the potential involvement of the thalamus, a structure viewed historically as a passive gateway in the brain, and the pallidum, a region linked to reward response and positive affect. Future functional and connectivity studies of suicidal behaviors may focus on understanding how these regions relate to the neurobiological mechanisms of suicide attempt risk.

  View details for DOI 10.1016/j.biopsych.2021.03.015

  View details for PubMedID 34172278

• Cortical thickness across the lifespan: Data from 17,075 healthy individuals aged 3-90years. Human brain mapping Frangou, S., Modabbernia, A., Williams, S. C., Papachristou, E., Doucet, G. E., Agartz, I., Aghajani, M., Akudjedu, T. N., Albajes-Eizagirre, A., Alnaes, D., Alpert, K. I., Andersson, M., Andreasen, N. C., Andreassen, O. A., Asherson, P., Banaschewski, T., Bargallo, N., Baumeister, S., Baur-Streubel, R., Bertolino, A., Bonvino, A., Boomsma, D. I., Borgwardt, S., Bourque, J., Brandeis, D., Breier, A., Brodaty, H., Brouwer, R. M., Buitelaar, J. K., Busatto, G. F., Buckner, R. L., Calhoun, V., Canales-Rodriguez, E. J., Cannon, D. M., Caseras, X., Castellanos, F. X., Cervenka, S., Chaim-Avancini, T. M., Ching, C. R., Chubar, V., Clark, V. P., Conrod, P., Conzelmann, A., Crespo-Facorro, B., Crivello, F., Crone, E. A., Dale, A. M., Davey, C., de Geus, E. J., de Haan, L., de Zubicaray, G. I., den Braber, A., Dickie, E. W., Di Giorgio, A., Doan, N. T., Dorum, E. S., Ehrlich, S., Erk, S., Espeseth, T., Fatouros-Bergman, H., Fisher, S. E., Fouche, J., Franke, B., Frodl, T., Fuentes-Claramonte, P., Glahn, D. C., Gotlib, I. H., Grabe, H., Grimm, O., Groenewold, N. A., Grotegerd, D., Gruber, O., Gruner, P., Gur, R. E., Gur, R. C., Harrison, B. J., Hartman, C. A., Hatton, S. N., Heinz, A., Heslenfeld, D. J., Hibar, D. P., Hickie, I. B., Ho, B., Hoekstra, P. J., Hohmann, S., Holmes, A. J., Hoogman, M., Hosten, N., Howells, F. M., Hulshoff Pol, H. E., Huyser, C., Jahanshad, N., James, A., Jernigan, T. L., Jiang, J., Jonsson, E. G., Joska, J. A., Kahn, R., Kalnin, A., Kanai, R., Klein, M., Klyushnik, T. P., Koenders, L., Koops, S., Kramer, B., Kuntsi, J., Lagopoulos, J., Lazaro, L., Lebedeva, I., Lee, W. H., Lesch, K., Lochner, C., Machielsen, M. W., Maingault, S., Martin, N. G., Martinez-Zalacain, I., Mataix-Cols, D., Mazoyer, B., McDonald, C., McDonald, B. C., McIntosh, A. M., McMahon, K. L., McPhilemy, G., Menchon, J. M., Medland, S. E., Meyer-Lindenberg, A., Naaijen, J., Najt, P., Nakao, T., Nordvik, J. E., Nyberg, L., Oosterlaan, J., de la Foz, V. O., Paloyelis, Y., Pauli, P., Pergola, G., Pomarol-Clotet, E., Portella, M. J., Potkin, S. G., Radua, J., Reif, A., Rinker, D. A., Roffman, J. L., Rosa, P. G., Sacchet, M. D., Sachdev, P. S., Salvador, R., Sanchez-Juan, P., Sarro, S., Satterthwaite, T. D., Saykin, A. J., Serpa, M. H., Schmaal, L., Schnell, K., Schumann, G., Sim, K., Smoller, J. W., Sommer, I., Soriano-Mas, C., Stein, D. J., Strike, L. T., Swagerman, S. C., Tamnes, C. K., Temmingh, H. S., Thomopoulos, S. I., Tomyshev, A. S., Tordesillas-Gutierrez, D., Trollor, J. N., Turner, J. A., Uhlmann, A., van den Heuvel, O. A., van den Meer, D., van der Wee, N. J., van Haren, N. E., van 't Ent, D., van Erp, T. G., Veer, I. M., Veltman, D. J., Voineskos, A., Volzke, H., Walter, H., Walton, E., Wang, L., Wang, Y., Wassink, T. H., Weber, B., Wen, W., West, J. D., Westlye, L. T., Whalley, H., Wierenga, L. M., Wittfeld, K., Wolf, D. H., Worker, A., Wright, M. J., Yang, K., Yoncheva, Y., Zanetti, M. V., Ziegler, G. C., Karolinska Schizophrenia Project (KaSP), Thompson, P. M., Dima, D. 2021

  Abstract

  Delineating the association of age and cortical thickness in healthy individuals is critical given the association of cortical thickness with cognition and behavior. Previous research has shown that robust estimates of the association between age and brain morphometry require large-scale studies. In response, we used cross-sectional data from 17,075 individuals aged 3-90years from the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to infer age-related changes in cortical thickness. We used fractional polynomial (FP) regression to quantify the association between age and cortical thickness, and we computed normalized growth centiles using the parametric Lambda, Mu, and Sigma method. Interindividual variability was estimated using meta-analysis and one-way analysis of variance. For most regions, their highest cortical thickness value was observed in childhood. Age and cortical thickness showed a negative association; the slope was steeper up to the third decade of life and more gradual thereafter; notable exceptions to this general pattern were entorhinal, temporopolar, and anterior cingulate cortices. Interindividual variability was largest in temporal and frontal regions across the lifespan. Age and its FP combinations explained up to 59% variance in cortical thickness. These results may form the basis of further investigation on normative deviation in cortical thickness and its significance for behavioral and cognitive outcomes.

  View details for DOI 10.1002/hbm.25364

  View details for PubMedID 33595143

• Subcortical volumes across the lifespan: Data from 18,605 healthy individuals aged 3-90years. Human brain mapping Dima, D., Modabbernia, A., Papachristou, E., Doucet, G. E., Agartz, I., Aghajani, M., Akudjedu, T. N., Albajes-Eizagirre, A., Alnaes, D., Alpert, K. I., Andersson, M., Andreasen, N. C., Andreassen, O. A., Asherson, P., Banaschewski, T., Bargallo, N., Baumeister, S., Baur-Streubel, R., Bertolino, A., Bonvino, A., Boomsma, D. I., Borgwardt, S., Bourque, J., Brandeis, D., Breier, A., Brodaty, H., Brouwer, R. M., Buitelaar, J. K., Busatto, G. F., Buckner, R. L., Calhoun, V., Canales-Rodriguez, E. J., Cannon, D. M., Caseras, X., Castellanos, F. X., Cervenka, S., Chaim-Avancini, T. M., Ching, C. R., Chubar, V., Clark, V. P., Conrod, P., Conzelmann, A., Crespo-Facorro, B., Crivello, F., Crone, E. A., Dale, A. M., Davey, C., de Geus, E. J., de Haan, L., de Zubicaray, G. I., den Braber, A., Dickie, E. W., Di Giorgio, A., Doan, N. T., Dorum, E. S., Ehrlich, S., Erk, S., Espeseth, T., Fatouros-Bergman, H., Fisher, S. E., Fouche, J., Franke, B., Frodl, T., Fuentes-Claramonte, P., Glahn, D. C., Gotlib, I. H., Grabe, H., Grimm, O., Groenewold, N. A., Grotegerd, D., Gruber, O., Gruner, P., Gur, R. E., Gur, R. C., Harrison, B. J., Hartman, C. A., Hatton, S. N., Heinz, A., Heslenfeld, D. J., Hibar, D. P., Hickie, I. B., Ho, B., Hoekstra, P. J., Hohmann, S., Holmes, A. J., Hoogman, M., Hosten, N., Howells, F. M., Hulshoff Pol, H. E., Huyser, C., Jahanshad, N., James, A., Jernigan, T. L., Jiang, J., Jonsson, E. G., Joska, J. A., Kahn, R., Kalnin, A., Kanai, R., Klein, M., Klyushnik, T. P., Koenders, L., Koops, S., Kramer, B., Kuntsi, J., Lagopoulos, J., Lazaro, L., Lebedeva, I., Lee, W. H., Lesch, K., Lochner, C., Machielsen, M. W., Maingault, S., Martin, N. G., Martinez-Zalacain, I., Mataix-Cols, D., Mazoyer, B., McDonald, C., McDonald, B. C., McIntosh, A. M., McMahon, K. L., McPhilemy, G., Menchon, J. M., Medland, S. E., Meyer-Lindenberg, A., Naaijen, J., Najt, P., Nakao, T., Nordvik, J. E., Nyberg, L., Oosterlaan, J., de la Foz, V. O., Paloyelis, Y., Pauli, P., Pergola, G., Pomarol-Clotet, E., Portella, M. J., Potkin, S. G., Radua, J., Reif, A., Rinker, D. A., Roffman, J. L., Rosa, P. G., Sacchet, M. D., Sachdev, P. S., Salvador, R., Sanchez-Juan, P., Sarro, S., Satterthwaite, T. D., Saykin, A. J., Serpa, M. H., Schmaal, L., Schnell, K., Schumann, G., Sim, K., Smoller, J. W., Sommer, I., Soriano-Mas, C., Stein, D. J., Strike, L. T., Swagerman, S. C., Tamnes, C. K., Temmingh, H. S., Thomopoulos, S. I., Tomyshev, A. S., Tordesillas-Gutierrez, D., Trollor, J. N., Turner, J. A., Uhlmann, A., van den Heuvel, O. A., van den Meer, D., van der Wee, N. J., van Haren, N. E., Van't Ent, D., van Erp, T. G., Veer, I. M., Veltman, D. J., Voineskos, A., Volzke, H., Walter, H., Walton, E., Wang, L., Wang, Y., Wassink, T. H., Weber, B., Wen, W., West, J. D., Westlye, L. T., Whalley, H., Wierenga, L. M., Williams, S. C., Wittfeld, K., Wolf, D. H., Worker, A., Wright, M. J., Yang, K., Yoncheva, Y., Zanetti, M. V., Ziegler, G. C., Thompson, P. M., Frangou, S., Karolinska Schizophrenia Project (KaSP) 2021

  Abstract

  Age has a major effect on brain volume. However, the normative studies available are constrained by small sample sizes, restricted age coverage and significant methodological variability. These limitations introduce inconsistencies and may obscure or distort the lifespan trajectories of brain morphometry. In response, we capitalized on the resources of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to examine age-related trajectories inferred from cross-sectional measures of the ventricles, the basal ganglia (caudate, putamen, pallidum, and nucleus accumbens), the thalamus, hippocampus and amygdala using magnetic resonance imaging data obtained from 18,605 individuals aged 3-90years. All subcortical structure volumes were at their maximum value early in life. The volume of the basal ganglia showed a monotonic negative association with age thereafter; there was no significant association between age and the volumes of the thalamus, amygdala and the hippocampus (with some degree of decline in thalamus) until the sixth decade of life after which they also showed a steep negative association with age. The lateral ventricles showed continuous enlargement throughout the lifespan. Age was positively associated with inter-individual variability in the hippocampus and amygdala and the lateral ventricles. These results were robust to potential confounders and could be used to examine the functional significance of deviations from typical age-related morphometric patterns.

  View details for DOI 10.1002/hbm.25320

  View details for PubMedID 33570244

• Breastfeeding Difficulties Predict Mothers' Bonding with Their Infants from Birth to Age Six Months. Maternal and child health journal Roth, M. C., Humphreys, K. L., King, L. S., Gotlib, I. H., Robakis, T. K. 2021

  Abstract

  OBJECTIVES: We examined the association between breastfeeding difficulties and trajectories of bonding in the first 6 months postpartum.METHODS: Each month for the first 6 months following birth, 121 mothers of newborn infants (age=23-45years, M=32.31±4.79, 57% White, 23% Asian, 11% Hispanic, 9% Multiracial, 1% Black/African American) were invited to complete self-assessments of bonding. At the first postpartum assessment, mothers who intended to breastfeed also reported whether breastfeeding was more difficult than they had anticipated. We conducted linear mixed modelling to test whether early breastfeeding difficulty was associated with bonding trajectories and examined whether effects remained when accounting for postnatal depression symptoms.RESULTS: We found main effects of breastfeeding difficulty (beta=-.20, 95% CI [-.34, -.06]) and postpartum month (beta=.13, 95% CI [.07, .20]) on bonding. On average, women who reported breastfeeding difficulty reported lower bonding than women who did not (Cohen's d=-0.44, 95% CI [-0.81, -0.06]). Additional analyses indicated that, independent of breastfeeding difficulties, women who reported higher postnatal depressive symptoms across the first 6 months postpartum reported lower levels of bonding, on average. Further, within-individual decreases in postnatal depressive symptoms across the first six months were associated with relative improvements in bonding across this period.CONCLUSIONS FOR PRACTICE: Our findings suggest that mothers who experience breastfeeding difficulties are at risk for reduced bonding with their infants in the first 6 months after birth. Moreover, while postnatal depressive symptoms are also associated with reduced bonding, the effect of breastfeeding difficulties on bonding persists over and above the effect of postnatal depressive symptoms.

  View details for DOI 10.1007/s10995-020-03036-9

  View details for PubMedID 33528724

• The social ecology of childhood and early life adversity. Pediatric research Lopez, M., Ruiz, M. O., Rovnaghi, C. R., Tam, G. K., Hiscox, J., Gotlib, I. H., Barr, D. A., Carrion, V. G., Anand, K. J. 2021

  Abstract

  An increasing prevalence of early childhood adversity has reached epidemic proportions, creating a public health crisis. Rather than focusing only on adverse childhood experiences (ACEs) as the main lens for understanding early childhood experiences, detailed assessments of a child's social ecology are required to assess "early life adversity." These should also include the role of positive experiences, social relationships, and resilience-promoting factors. Comprehensive assessments of a child's physical and social ecology not only require parent/caregiver surveys and clinical observations, but also include measurements of the child's physiology using biomarkers. We identify cortisol as a stress biomarker and posit that hair cortisol concentrations represent a summative and chronological record of children's exposure to adverse experiences and other contextual stressors. Future research should use a social-ecological approach to investigate the robust interactions among adverse conditions, protective factors, genetic and epigenetic influences, environmental exposures, and social policy, within the context of a child's developmental stages. These contribute to their physical health, psychiatric conditions, cognitive/executive, social, and psychological functions, lifestyle choices, and socioeconomic outcomes. Such studies must inform preventive measures, therapeutic interventions, advocacy efforts, social policy changes, and public awareness campaigns to address early life adversities and their enduring effects on human potential. IMPACT: Current research does not support the practice of using ACEs as the main lens for understanding early childhood experiences. The social ecology of early childhood provides a contextual framework for evaluating the long-term health consequences of early life adversity. Comprehensive assessments reinforced with physiological measures and/or selected biomarkers, such as hair cortisol concentrations to assess early life stress, may provide critical insights into the relationships between early adversity, stress axis regulation, and subsequent health outcomes.

  View details for DOI 10.1038/s41390-020-01264-x

  View details for PubMedID 33462396

• Dimensions of the language environment in infancy and symptoms of psychopathology in toddlerhood. Developmental science King, L. S., Querdasi, F. R., Humphreys, K. L., Gotlib, I. H. 2021: e13082

  Abstract

  The quality of the early environment influences the development of psychopathology. Children who are deprived of sufficient environmental enrichment in infancy may be at higher risk for developing symptoms of psychopathology in toddlerhood. In this study, we investigated the prospective association between naturalistic measures of adult language input obtained through passive monitoring of infants' daily environments and emerging psychopathology in toddlerhood. In a sample of 100 mothers and their infants recruited from the community (mean age [range] = 6.73 [5-9] months), we used the Language ENvironment Analysis (LENA) system to measure multiple dimensions of infants' language environments, including both the quantity and consistency of adult speech and conversational turns in infants' daily lives as well as the quantity of infant vocalizations. Subsequently, during toddlerhood (mean age [range] = 18.29 [17-21] months), mothers reported on their children's symptoms of psychopathology. Infants who experienced more consistent adult speech and conversational turns had lower symptoms of psychopathology in toddlerhood, independent of negative emotionality in infancy, maternal depressive symptoms, and laboratory-based measures of maternal sensitivity. These findings have implications for the measurement of environmental factors that may confer risk and resilience to emerging psychopathology.

  View details for DOI 10.1111/desc.13082

  View details for PubMedID 33455064

• Default mode and salience network alterations in suicidal and non-suicidal self-injurious thoughts and behaviors in adolescents with depression. Translational psychiatry Ho, T. C., Walker, J. C., Teresi, G. I., Kulla, A., Kirshenbaum, J. S., Gifuni, A. J., Singh, M. K., Gotlib, I. H. 2021; 11 (1): 38

  Abstract

  Suicidal ideation (SI) and non-suicidal self-injury (NSSI) are two distinct yet often co-occurring risk factors for suicide deaths in adolescents. Elucidating the neurobiological patterns that specifically characterize SI and NSSI in adolescents is needed to inform the use of these markers in intervention studies and to develop brain-based treatment targets. Here, we clinically assessed 70 adolescents-49 adolescents with depression and 21 healthy controls-to determine SI and NSSI history. Twenty-eight of the depressed adolescents had a history of SI and 29 had a history of NSSI (20 overlapping). All participants underwent a resting-state fMRI scan. We compared groups in network coherence of subdivisions of the central executive network (CEN), default mode network (DMN), and salience network (SN). We also examined group differences in between-network connectivity and explored brain-behavior correlations. Depressed adolescents with SI and with NSSI had lower coherence in the ventral DMN compared to those without SI or NSSI, respectively, and healthy controls (all ps<0.043, uncorrected). Depressed adolescents with NSSI had lower coherence in the anterior DMN and in insula-SN (all ps<0.030, uncorrected), and higher CEN-DMN connectivity compared to those without NSSI and healthy controls (all ps<0.030, uncorrected). Lower network coherence in all DMN subnetworks and insula-SN were associated with higher past-month SI and NSSI (all ps<0.001, uncorrected). Thus, in our sample, both SI and NSSI are related to brain networks associated with difficulties in self-referential processing and future planning, while NSSI specifically is related to brain networks associated with disruptions in interoceptive awareness.

  View details for DOI 10.1038/s41398-020-01103-x

  View details for PubMedID 33436537

• Early Life Stress Predicts Depressive Symptoms in Adolescents During the COVID-19 Pandemic: The Mediating Role of Perceived Stress Frontiers in Psychology Gotlib, I. H., Borchers, L., Chahal, R., Gifuni, A., Teresi, G., Ho, T. 2021

  View details for DOI 10.3389/fpsyg.2020.603748

• Fine Particulate Air Pollution, Early Life Stress, and Their Interactive Effects on Adolescent Structural Brain Development: A Longitudinal Tensor-Based Morphometry Study. Cerebral cortex (New York, N.Y. : 1991) Miller, J. G., Dennis, E. L., Heft-Neal, S., Jo, B., Gotlib, I. H. 2021

  Abstract

  Air pollution is a major environmental threat to public health; we know little, however, about its effects on adolescent brain development. Exposure to air pollution co-occurs, and may interact, with social factors that also affect brain development, such as early life stress (ELS). Here, we show that severity of ELS and fine particulate air pollution (PM2.5) are associated with volumetric changes in distinct brain regions, but also uncover regions in which ELS moderates the effects of PM2.5. We interviewed adolescents about ELS events, used satellite-derived estimates of ambient PM2.5 concentrations, and conducted longitudinal tensor-based morphometry to assess regional changes in brain volume over an approximately 2-year period (N = 115, ages 9-13 years at Time 1). For adolescents who had experienced less severe ELS, PM2.5 was associated with volumetric changes across several gray and white matter regions. Fewer effects of PM2.5 were observed for adolescents who had experienced more severe ELS, although occasionally they were in the opposite direction. This pattern of results suggests that for many brain regions, moderate to severe ELS largely constrains the effects of PM2.5 on structural development. Further theory and research is needed on the joint effects of ELS and air pollution on the brain.

  View details for DOI 10.1093/cercor/bhab346

  View details for PubMedID 34607342

• Deleterious and Protective Psychosocial and Stress-Related Factors Predict Risk of Spontaneous Preterm Birth. American journal of perinatology Becker, M. n., Mayo, J. A., Phogat, N. K., Quaintance, C. C., Laborde, A. n., King, L. n., Gotlib, I. H., Gaudilliere, B. n., Angst, M. S., Shaw, G. M., Stevenson, D. K., Aghaeepour, N. n., Dhabhar, F. S. 2021

  Abstract

   The aim of the study was to: (1) Identify (early in pregnancy) psychosocial and stress-related factors that predict risk of spontaneous preterm birth (PTB, gestational age <37 weeks); (2) Investigate whether "protective" factors (e.g., happiness/social support) decrease risk; (3) Use the Dhabhar Quick-Assessment Questionnaire for Stress and Psychosocial Factors™ (DQAQ-SPF™) to rapidly quantify harmful or protective factors that predict increased or decreased risk respectively, of PTB. This is a prospective cohort study. Relative risk (RR) analyses investigated association between individual factors and PTB. Machine learning-based interdependency analysis (IDPA) identified factor clusters, strength, and direction of association with PTB. A nonlinear model based on support vector machines was built for predicting PTB and identifying factors that most strongly predicted PTB. Higher levels of deleterious factors were associated with increased RR for PTB: General anxiety (RR = 8.9; 95% confidence interval or CI = 2.0,39.6), pain (RR = 5.7; CI = 1.7,17.0); tiredness/fatigue (RR = 3.7; CI = 1.09,13.5); perceived risk of birth complications (RR = 4; CI = 1.6,10.01); self-rated health current (RR = 2.6; CI = 1.0,6.7) and previous 3 years (RR = 2.9; CI = 1.1,7.7); and divorce (RR = 2.9; CI = 1.1,7.8). Lower levels of protective factors were also associated with increased RR for PTB: low happiness (RR = 9.1; CI = 1.25,71.5); low support from parents/siblings (RR = 3.5; CI = 0.9,12.9), and father-of-baby (RR = 3; CI = 1.1,9.9). These factors were also components of the clusters identified by the IDPA: perceived risk of birth complications (p < 0.05 after FDR correction), and general anxiety, happiness, tiredness/fatigue, self-rated health, social support, pain, and sleep (p < 0.05 without FDR correction). Supervised analysis of all factors, subject to cross-validation, produced a model highly predictive of PTB (AUROC or area under the receiver operating characteristic = 0.73). Model reduction through forward selection revealed that even a small set of factors (including those identified by RR and IDPA) predicted PTB. These findings represent an important step toward identifying key factors, which can be assessed rapidly before/after conception, to predict risk of PTB, and perhaps other adverse pregnancy outcomes. Quantifying these factors, before, or early in pregnancy, could identify women at risk of delivering preterm, pinpoint mechanisms/targets for intervention, and facilitate the development of interventions to prevent PTB.· Newly designed questionnaire used for rapid quantification of stress and psychosocial factors early during pregnancy.. · Deleterious factors predict increased preterm birth (PTB) risk.. · Protective factors predict decreased PTB risk..

  View details for DOI 10.1055/s-0041-1729162

  View details for PubMedID 34015838

• Heart rate variability moderates the effects of COVID-19-related stress and family adversity on emotional problems in adolescents: Testing models of differential susceptibility and diathesis stress. Development and psychopathology Miller, J. G., Chahal, R., Kirshenbaum, J. S., Ho, T. C., Gifuni, A. J., Gotlib, I. H. 2021: 1-12

  Abstract

  The COVID-19 pandemic is a unique period of stress, uncertainty, and adversity that will have significant implications for adolescent mental health. Nevertheless, stress and adversity related to COVID-19 may be more consequential for some adolescents' mental health than for others. We examined whether heart rate variability (HRV) indicated differential susceptibility to mental health difficulties associated with COVID-19 stress and COVID-19 family adversity. Approximately 4 years prior to the pandemic, we assessed resting HRV and HRV reactivity to a well-validated stress paradigm in 87 adolescents. During the pandemic, these adolescents (ages 13-19) reported on their health-related stress and concerns about COVID-19, family adversity related to COVID-19, and their recent emotional problems. The association between COVID-19 stress and emotional problems was significantly stronger for adolescents who previously exhibited higher resting HRV or higher HRV reactivity. For adolescents who exhibited lower resting HRV or HRV augmentation, COVID-19 stress was not associated with emotional problems. Conversely, lower resting HRV indicated vulnerability to the effect of COVID-19 family adversity on emotional problems. Different patterns of parasympathetic functioning may reflect differential susceptibility to the effects of COVID-19 stress versus vulnerability to the effects of COVID-19 family adversity on mental health during the pandemic.

  View details for DOI 10.1017/S095457942100033X

  View details for PubMedID 34099071

• Higher Levels of Pro-inflammatory Cytokines Are Associated With Higher Levels of Glutamate in the Anterior Cingulate Cortex in Depressed Adolescents. Frontiers in psychiatry Ho, T. C., Teresi, G. I., Segarra, J. R., Ojha, A., Walker, J. C., Gu, M., Spielman, D. M., Sacchet, M. D., Jiang, F., Rosenberg-Hasson, Y., Maecker, H., Gotlib, I. H. 2021; 12: 642976

  Abstract

  Animal models of stress and related conditions, including depression, have shown that elevated peripheral levels of inflammatory cytokines have downstream consequences on glutamate (Glu) in the brain. Although studies in human adults with depression have reported evidence of higher inflammation but lower Glu in the anterior cingulate cortex (ACC), the extent to which peripheral inflammation contributes to glutamatergic abnormalities in adolescents with depression is not well-understood. It is also unclear whether antioxidants, such as ascorbate (Asc), may buffer against the effects of inflammation on Glu metabolism. Fifty-five depressed adolescents were recruited in the present cross-sectional study and provided blood samples, from which we assayed pro-inflammatory cytokines, and underwent a short-TE proton magnetic spectroscopy scan at 3T, from which we estimated Glu and Asc in the dorsal ACC. In the 31 adolescents with usable cytokine and Glu data, we found that IL-6 was significantly positively associated with dorsal ACC Glu (beta = 0.466 ± 0.199, p = 0.029). Of the 16 participants who had usable Asc data, we found that at higher levels of dorsal ACC Asc, there was a negative association between IL-6 and Glu (interaction effect: beta = -0.906 ± 0.433, p = 0.034). Importantly, these results remained significant when controlling for age, gender, percentage of gray matter in the dorsal ACC voxel, BMI, and medication (antidepressant and anti-inflammatory) usage. While preliminary, our results underscore the importance of examining both immune and neural contributors to depression and highlight the potential role of anti-inflammatory compounds in mitigating the adverse effects of inflammation (e.g., glutamatergic neuroexcitotoxicity). Future studies that experimentally manipulate levels of inflammation, and of ascorbate, and that characterize these effects on cortical glutamate concentrations and subsequent behavior in animals and in humans are needed.

  View details for DOI 10.3389/fpsyt.2021.642976

  View details for PubMedID 33935833

• Functional network alterations differently associated with suicidal ideas and acts in depressed patients: an indirect support to the transition model. Translational psychiatry Wagner, G. n., Li, M. n., Sacchet, M. D., Richard-Devantoy, S. n., Turecki, G. n., Bär, K. J., Gotlib, I. H., Walter, M. n., Jollant, F. n. 2021; 11 (1): 100

  Abstract

  The transition from suicidal ideas to a suicide act is an important topic of research for the identification of those patients at risk of acting out. We investigated here whether specific brain activity and connectivity measures at rest may be differently associated with suicidal thoughts and behaviors. A large sample of acutely depressed patients with major depressive disorder was recruited in three different centers (Montreal/Canada, Stanford/USA, and Jena/Germany), covering four different phenotypes: patients with a past history of suicide attempt (n = 53), patients with current suicidal ideas but no past history of suicide attempt (n = 40), patients without current suicidal ideation nor past suicide attempts (n = 42), and healthy comparison subjects (n = 107). 3-T resting-state functional magnetic resonance imaging (fMRI) measures of the amplitude of low-frequency fluctuation (ALFF) and degree centrality (DC) were obtained and examined in a whole-brain data-driven analysis. Past suicide attempt was associated with a double cortico-subcortical dissociation in ALFF values. Decreased ALFF and DC values mainly in a frontoparietal network and increased ALFF values in some subcortical regions (hippocampus and thalamus) distinguished suicide attempters from suicide ideators, patient controls, and healthy controls. No clear neural differences were identified in relation to suicidal ideas. Suicide attempters appear to be a distinct subgroup of patients with widespread brain alterations in functional activity and connectivity that could represent factors of vulnerability. Our results also indirectly support at the neurobiological level the relevance of the transition model described at the psychological and clinical levels. The brain bases of suicidal ideas occurrence in depressed individuals needs further investigations.

  View details for DOI 10.1038/s41398-021-01232-x

  View details for PubMedID 33542184

• Prenatal and postnatal depressive symptoms, infant white matter, and toddler behavioral problems. Journal of affective disorders Borchers, L. R., Dennis, E. L., King, L. S., Humphreys, K. L., Gotlib, I. H. 2020; 282: 465–71

  Abstract

  BACKGROUND: Maternal depression is prevalent during and following pregnancy and is related to adverse outcomes in offspring. Perinatal depression is associated with risk for difficulties in offspring; however, the mechanisms underlying this association are not clear. We examined whether maternal prenatal and postnatal depressive symptoms were associated with infant white matter organization and with behavioral problems in toddlerhood.METHODS: 37 mother-infant dyads (20 male; ages 5.95-7.66 months) participated in this study. We conducted diffusion MRI with infants during natural sleep. Mothers reported on their prenatal and postnatal depressive symptoms at six months postpartum. We calculated fractional anisotropy (FA), radial, axial, and mean diffusivity, and assessed offspring behavioral problems at age 18 months.RESULTS: Prenatal depressive symptoms were associated with FA of the corpus callosum; postnatal depressive symptoms were not associated with FA of limbic tracts or corpus callosum segmentations. Higher levels of prenatal depressive symptoms were associated with higher FA and lower radial diffusivity of the corpus callosum genu; FA of this region was positively associated with behavioral problems at age 18 months.LIMITATIONS: This study had a small sample size; therefore, findings should be replicated. Further, we used retrospective reports of maternal prenatal depression, but validated them in this study.CONCLUSIONS: Depressive symptoms during pregnancy may affect infant corpus callosum development and, in turn, offspring behaviors. These findings suggest that early maternal stress accelerates infant neurodevelopment in a manner that may increase risk for behavioral problems. Thus, efforts to reduce maternal prenatal depression should be a public health priority.

  View details for DOI 10.1016/j.jad.2020.12.075

  View details for PubMedID 33422824

• Brain structural correlates of insomnia severity in 1053 individuals with major depressive disorder: results from the ENIGMA MDD Working Group. Translational psychiatry Leerssen, J., Blanken, T. F., Pozzi, E., Jahanshad, N., Aftanas, L., Andreassen, O. A., Baune, B. T., Brack, I., Carballedo, A., Ching, C. R., Dannlowski, U., Dohm, K., Enneking, V., Filimonova, E., Fingas, S. M., Frodl, T., Godlewska, B. R., Goltermann, J., Gotlib, I. H., Grotegerd, D., Gruber, O., Harris, M. A., Hatton, S. N., Hawkins, E., Hickie, I. B., Jaworska, N., Kircher, T., Krug, A., Lagopoulos, J., Lemke, H., Li, M., MacMaster, F. P., McIntosh, A. M., McLellan, Q., Meinert, S., Mwangi, B., Nenadic, I., Osipov, E., Portella, M. J., Redlich, R., Repple, J., Sacchet, M. D., Samann, P. G., Simulionyte, E., Soares, J. C., Walter, M., Watanabe, N., Whalley, H. C., Yuksel, D., Veltman, D. J., Thompson, P. M., Schmaal, L., Van Someren, E. J. 2020; 10 (1): 425

  Abstract

  It has been difficult to find robust brain structural correlates of the overall severity of major depressive disorder (MDD). We hypothesized that specific symptoms may better reveal correlates and investigated this for the severity of insomnia, both a key symptom and a modifiable major risk factor of MDD. Cortical thickness, surface area and subcortical volumes were assessed from T1-weighted brain magnetic resonance imaging (MRI) scans of 1053 MDD patients (age range 13-79 years) from 15 cohorts within the ENIGMA MDD Working Group. Insomnia severity was measured by summing the insomnia items of the Hamilton Depression Rating Scale (HDRS). Symptom specificity was evaluated with correlates of overall depression severity. Disease specificity was evaluated in two independent samples comprising 2108 healthy controls, and in 260 clinical controls with bipolar disorder. Results showed that MDD patients with more severe insomnia had a smaller cortical surface area, mostly driven by the right insula, left inferior frontal gyrus pars triangularis, left frontal pole, right superior parietal cortex, right medial orbitofrontal cortex, and right supramarginal gyrus. Associations were specific for insomnia severity, and were not found for overall depression severity. Associations were also specific to MDD; healthy controls and clinical controls showed differential insomnia severity association profiles. The findings indicate that MDD patients with more severe insomnia show smaller surfaces in several frontoparietal cortical areas. While explained variance remains small, symptom-specific associations could bring us closer to clues on underlying biological phenomena of MDD.

  View details for DOI 10.1038/s41398-020-01109-5

  View details for PubMedID 33293520

• Sympathetic nervous system dominance during stress recovery mediates associations between stress sensitivity and social anxiety symptoms in female adolescents. Development and psychopathology Ho, T. C., Pham, H. T., Miller, J. G., Kircanski, K., Gotlib, I. H. 2020; 32 (5): 1914–25

  Abstract

  Social anxiety disorder (SAD) is commonly diagnosed during adolescence and is associated with psychological stress reactivity and heightened physiological arousal. No study, however, has systematically examined which aspects of autonomic nervous system function mediate likely links between stress sensitivity and social anxiety symptoms in adolescents. Here, we assessed 163 adolescents (90 females; 12.29 ± 1.39 years) with respect to life stress and social anxiety symptoms, and measured respiratory sinus arrhythmia (RSA) and skin conductance levels (SCL) during a psychosocial stress paradigm. We operationalized stress sensitivity as the residual variance in subjective stress severity after accounting for objective severity and changes in autonomic regulation using standardized change scores in RSA and SCL. In females only, stress sensitivity and social anxiety symptoms were significantly correlated with each other (p < .001) and with autonomic regulation during both reactivity and recovery (all ps < 0.04). Further, sympathetic nervous system dominance during recovery specifically mediated associations between stress sensitivity and social anxiety symptoms (B = 1.06, 95% CI: 0.02-2.64). In contrast, in males, stress sensitivity, autonomic regulation during reactivity or recovery, and social anxiety symptoms were not significantly associated (all ps > 0.1). We interpret these results in the context of psychobiological models of SAD and discuss implications for interventions targeting autonomic processes.

  View details for DOI 10.1017/S0954579420001261

  View details for PubMedID 33427188

• Naturalistic Language Input is Associated with Resting-State Functional Connectivity in Infancy. The Journal of neuroscience : the official journal of the Society for Neuroscience King, L. S., Camacho, M. C., Montez, D. F., Humphreys, K. L., Gotlib, I. H. 2020

  Abstract

  The quantity and quality of the language input that infants receive from their caregivers affects their future language abilities; however, it is unclear how variation in this input relates to preverbal brain circuitry. The current study investigated the relation between naturalistic language input and the functional connectivity of language networks in human infancy using resting-state functional magnetic resonance imaging (rsfMRI). We recorded the naturalistic language environments of 5- to 8-month-old male and female infants using the Linguistic Environment Analysis (LENA) system and measured the quantity and consistency of their exposure to adult words and adult-infant conversational turns. Infants completed an rsfMRI scan during natural sleep and we examined functional connectivity among regions of interest previously implicated in language comprehension, including the auditory cortex, the left inferior frontal gyrus (IFG), and the bilateral superior temporal gyrus (STG). Consistent with theory of the ontogeny of the cortical language network (Skeide and Friederici, 2016), we identified two subnetworks posited to have distinct developmental trajectories: a posterior temporal network involving connections of the auditory cortex and bilateral STG and a frontotemporal network involving connections of the left IFG. Independent of socioeconomic status, the quantity of conversational turns was uniquely associated with functional connectivity of these networks. Infants who engaged in a larger number of conversational turns in daily life had lower connectivity in the posterior temporal language network. These results provide evidence for the role of vocal interactions with caregivers, compared to overheard adult speech, in the function of language networks in infancy.SIGNIFICANCE STATEMENT Infants whose caregivers speak to them more develop better language skills. It is unclear, however, how real-word language input is associated with preverbal brain circuitry. Resting-state functional magnetic resonance imaging during natural sleep can noninvasively measure patterns of brain activation in infancy. The present study finds that the quantity of vocal interactions infants engage in with their caregivers in daily life correlates with the strength of resting-state functional connectivity in regions of the brain implicated in language comprehension. These results provide evidence for the role of vocal interactions with caregivers in the function of language networks in infancy. Interventions that focus on increasing vocal interactions may be associated with infant brain function in a manner that ultimately enhances language abilities.

  View details for DOI 10.1523/JNEUROSCI.0779-20.2020

  View details for PubMedID 33257324

• White-matter tract connecting anterior insula to nucleus accumbens predicts greater future motivation in adolescents. Developmental cognitive neuroscience Leong, J. K., Ho, T. C., Colich, N. L., Sisk, L., Knutson, B., Gotlib, I. H. 2020; 47: 100881

  Abstract

  The motivation to approach or avoid incentives can change during adolescence. Advances in neuroimaging allow researchers to characterize specific brain circuits that underlie these developmental changes. Whereas activity in the nucleus accumbens (NAcc) can predict approach toward incentive gain, activity in anterior insula (AIns) is associated with avoidance of incentive loss. Recent research characterized the structural white-matter tract connecting the two brain regions, but the tract has neither been characterized in adolescence nor linked to functional activity during incentive anticipation. In this study, we collected diffusion MRI and characterized the tract connecting the AIns to the NAcc for the first time in early adolescents. We then measured NAcc functional activity during a monetary incentive delay task and found that structural coherence of the AIns-NAcc tract is correlated with decreased functional activity at the NAcc terminal of the tract during anticipation of no incentives. In adolescents who completed an assessment 2 years later, we found that AIns-NAcc tract coherence could predict greater future self-reported motivation, and that NAcc functional activity could statistically mediate this association. Together, the findings establish links from brain structure to function to future motivation and provide targets to study the reciprocal development of brain structure and function.

  View details for DOI 10.1016/j.dcn.2020.100881

  View details for PubMedID 33373886

• Air pollution is associated with elevated HPA-Axis response to stress in anxious adolescent girls. Comprehensive psychoneuroendocrinology Miller, J. G., Gillette, J. S., Kircanski, K., LeMoult, J., Gotlib, I. H. 2020; 4: 100015

  Abstract

  Research suggests that exposure to fine particulate air pollution (PM2.5) increases hypothalamic-pituitary-adrenal (HPA) axis activation in adults; it is unclear, however, whether PM2.5 is associated with HPA-axis functioning in psychosocial contexts, such as during the experience of social stress. One recent study of adolescents found that PM2.5 was associated with heightened autonomic reactivity to a social stress task, and that this association was strongest for adolescents with more severe internalizing symptoms. Here, we sought to replicate and extend these findings to HPA-axis stress responsivity in an independent sample of adolescent girls (N ​= ​130). We estimated PM2.5 concentrations at each participant's address using data from nearby air quality monitoring stations, and assessed participants' anxiety symptoms. We measured salivary cortisol in response to a social stress task and characterized HPA-axis functioning by computing area under the curve with respect to ground (AUCg) and with respect to increase (AUCi). Controlling for demographic factors, we found that PM2.5 was associated with heightened HPA-axis stress responsivity (both AUCg and AUCi) for girls who reported more severe levels of anxiety. We did not find a main effect of PM2.5 on HPA-axis functioning. These findings suggest that anxious adolescents are particularly vulnerable to the adverse effects of PM2.5 exposure on biological sensitivity to social stress.

  View details for DOI 10.1016/j.cpnec.2020.100015

  View details for PubMedID 35755623

  View details for PubMedCentralID PMC9216601

• A Comparison of Quantitative R1 and Cortical Thickness in Identifying Age, Lifespan Dynamics, and Disease States of the Human Cortex. Cerebral cortex (New York, N.Y. : 1991) Erramuzpe, A., Schurr, R., Yeatman, J. D., Gotlib, I. H., Sacchet, M. D., Travis, K. E., Feldman, H. M., Mezer, A. A. 2020

  Abstract

  Brain development and aging are complex processes that unfold in multiple brain regions simultaneously. Recently, models of brain age prediction have aroused great interest, as these models can potentially help to understand neurological diseases and elucidate basic neurobiological mechanisms. We test whether quantitative magnetic resonance imaging can contribute to such age prediction models. Using R1, the longitudinal rate of relaxation, we explore lifespan dynamics in cortical gray matter. We compare R1 with cortical thickness, a well-established biomarker of brain development and aging. Using 160 healthy individuals (6-81 years old), we found that R1 and cortical thickness predicted age similarly, but the regions contributing to the prediction differed. Next, we characterized R1 development and aging dynamics. Compared with anterior regions, in posterior regions we found an earlier R1 peak but a steeper postpeak decline. We replicate these findings: firstly, we tested a subset (N=10) of the original dataset for whom we had additional scans at a lower resolution; and second, we verified the results on an independent dataset (N=34). Finally, we compared the age prediction models on a subset of 10 patients with multiple sclerosis. The patients are predicted older than their chronological age using R1 but not with cortical thickness.

  View details for DOI 10.1093/cercor/bhaa288

  View details for PubMedID 33095854

• Study Protocol for Teen Inflammation Glutamate Emotion Research (TIGER) FRONTIERS IN HUMAN NEUROSCIENCE Walker, J. C., Teresi, G. I., Weisenburger, R. L., Segarra, J. R., Ojha, A., Kulla, A., Sisk, L., Gu, M., Spielman, D. M., Rosenberg-Hasson, Y., Maecker, H. T., Singh, M. K., Gotlib, I. H., Ho, T. C. 2020; 14

  View details for DOI 10.3389/fnhum.2020.585512

  View details for Web of Science ID 000583260500001

• Study Protocol for Teen Inflammation Glutamate Emotion Research (TIGER). Frontiers in human neuroscience Walker, J. C., Teresi, G. I., Weisenburger, R. L., Segarra, J. R., Ojha, A., Kulla, A., Sisk, L., Gu, M., Spielman, D. M., Rosenberg-Hasson, Y., Maecker, H. T., Singh, M. K., Gotlib, I. H., Ho, T. C. 2020; 14: 585512

  Abstract

  This article provides an overview of the study protocol for the Teen Inflammation Glutamate Emotion Research (TIGER) project, a longitudinal study in which we plan to recruit 60 depressed adolescents (ages 13-18 years) and 30 psychiatrically healthy controls in order to examine the inflammatory and glutamatergic pathways that contribute to the recurrence of depression in adolescents. TIGER is the first study to examine the effects of peripheral inflammation on neurodevelopmental trajectories by assessing changes in cortical glutamate in depressed adolescents. Here, we describe the scientific rationale, design, and methods for the TIGER project. This article is intended to serve as an introduction to this project and to provide details for investigators who may be seeking to replicate or extend these methods for other related research endeavors.

  View details for DOI 10.3389/fnhum.2020.585512

  View details for PubMedID 33192421

  View details for PubMedCentralID PMC7604389

• Attachment Security in Pregnancy Mediates the Association Between Maternal Childhood Maltreatment and Emotional and Behavioral Problems in Offspring. Child psychiatry and human development Roth, M. C., Humphreys, K. L., King, L. S., Mondal, S., Gotlib, I. H., Robakis, T. 2020

  Abstract

  Attachment security may be a mechanism by which exposure to early life adversity affects subsequent generations. We used a prospective cohort design to examine this possibility in a convenience sample of 124 women (age=23-45 years, M=32.32 [SD=4.83] years; 57.3% White, 22.6% Asian) who provided self-reports of attachment style during pregnancy using the Attachment Style Questionnaire, of whom 96 (age=28-50 years, M=36.67 [SD=4.90] years; 60.4% White, 19.8% Asian) were reassessed when their child was preschool-age (M=4.38 [SD=1.29] years). Women self-reported on their own childhood maltreatment severity and their child's current emotional and behavioral problems using the Childhood Trauma Questionnaire and the Child Behavior Checklist for ages 1.5-5, respectively. Maternal childhood maltreatment severity was associated with less secure, and more avoidant and anxious attachment. Mediation analyses revealed further that less secure maternal attachment, but not avoidant or anxious attachment, mediated the associations between maternal childhood maltreatment and offspring emotional and behavioral problems. These findings suggest that improving maternal attachment security, which can be identified even prior to the child's birth, is an important target to consider for intervention efforts aimed at minimizing adverse intergenerational effects of early life adversity.

  View details for DOI 10.1007/s10578-020-01073-7

  View details for PubMedID 33047183

• EARLY-LIFE STRESS DIFFERENTIALLY AFFECTS WHITE MATTER TRACTS IN MALES AND FEMALES DURING EARLY PUBERTY: ASSOCIATIONS WITH INTERNALIZING AND EXTERNALIZING PROBLEMS Chahal, R., Kirshenbaum, J., Mastrovito, D., Gotlib, I. ELSEVIER SCIENCE INC. 2020: S320

  View details for DOI 10.1016/j.jaac.2020.07.755

  View details for Web of Science ID 000579844101452

• Standards for Socially-and Achievement-Oriented Roles in Major Depressive Disorder and Generalized Anxiety Disorder. Cognitive therapy and research Thompson, R. J., Borenstein, J. B., Kircanski, K., Gotlib, I. H. 2020; 44 (5): 1025-1033

  Abstract

  People with major depressive disorder (MDD) and generalized anxiety disorder (GAD) have elevated trait perfectionism. We tested whether they hold perfectionistic standards for specific life roles and examined the extent to which they met their own expectations for, gained satisfaction from, and expended effort in these roles.Seventy-four women with MDD, GAD, both disorders, or no mental disorders (CTL) described their standards for a socially- and achievement-oriented roles, coded for perfectionism. Using ecological momentary assessment, participants reported the extent to which they met, how much satisfaction they gained from, and how much effort they expended in each role.Although the clinical groups endorsed elevated trait perfectionism, they did not differ from CTLs in their role-specific standards. Compared to CTLs, the clinical groups reported meeting their standards to a lesser extent and receiving less satisfaction from both roles. The two MDD groups reported expending less effort in achievement-oriented, but not socially-oriented, roles than the other two groups.Despite similar standards for socially- and achievement-oriented roles, people with MDD and/or GAD are less likely to meet their standards and gain satisfaction from these roles. Having MDD, independent of GAD, is associated with putting less effort into achievement-oriented roles.

  View details for DOI 10.1007/s10608-020-10123-2

  View details for PubMedID 33551520

  View details for PubMedCentralID PMC7864562

• The structure of depressive symptoms and characteristics and their relation to overall severity in major depressive disorder. Psychiatry research Miller, C. H., Davis, E. G., King, L. S., Sacchet, M. D., Grill-Spector, K., Gotlib, I. H. 2020; 294: 113399

  Abstract

  Although many investigators have examined symptoms of major depressive disorder (MDD), the multivariate relations among these features of depression and their relative associations with overall severity of depression are not well understood. The present study is the first to examine the underlying factor structure of depression across a broad set of constructs and to model the multivariate association of these factors with the overall severity of depression. We conducted a large-scale factor analysis and multiple regression in a sample of participants diagnosed with MDD (N=233) and healthy controls (N=235). We obtained a five-factor solution composed of the following factors: (1) anxiety; (2) behavioral activation; (3) core symptoms; (4) rumination; and (5) emotional intensity. The core symptoms factor, composed primarily of DSM-5 diagnostic criteria for MDD, was the only factor that showed a consistent, significant association with overall severity of depression and functional impairment. Rumination combined with behavioral inhibition and positive and negative affect combined with each other to form coherent constructs that may be useful in examining differences among depressed individuals. These findings provide an important data-driven framework for the multidimensional symptom structure of depression and suggest several actionable ways for improving clinical assessment and treatment for individuals with MDD.

  View details for DOI 10.1016/j.psychres.2020.113399

  View details for PubMedID 33070106

• PROSPECTIVE ASSOCIATIONS BETWEEN LIPID PROFILES AT BIRTH AND MENTAL HEALTH AT SCHOOL ENTRY Manczak, E., Gotlib, I. LIPPINCOTT WILLIAMS & WILKINS. 2020: A191–A192

  View details for Web of Science ID 000549961200531

• Support Vector Machines and Affective Science EMOTION REVIEW Miller, C. H., Sacchet, M. D., Gotlib, I. H. 2020

  View details for DOI 10.1177/1754073920930784

  View details for Web of Science ID 000542320400001

• Standards for Socially-and Achievement-Oriented Roles in Major Depressive Disorder and Generalized Anxiety Disorder COGNITIVE THERAPY AND RESEARCH Thompson, R. J., Borenstein, J. B., Kircanski, K., Gotlib, I. H. 2020

  View details for DOI 10.1007/s10608-020-10123-2

  View details for Web of Science ID 000542776500001

• Towards personalized medicine in maternal and child health: integrating biologic and social determinants. Pediatric research Stevenson, D. K., Wong, R. J., Aghaeepour, N., Maric, I., Angst, M. S., Contrepois, K., Darmstadt, G. L., Druzin, M. L., Eisenberg, M. L., Gaudilliere, B., Gibbs, R. S., Gotlib, I. H., Gould, J. B., Lee, H. C., Ling, X. B., Mayo, J. A., Moufarrej, M. N., Quaintance, C. C., Quake, S. R., Relman, D. A., Sirota, M., Snyder, M. P., Sylvester, K. G., Hao, S., Wise, P. H., Shaw, G. M., Katz, M. 2020

  View details for DOI 10.1038/s41390-020-0981-8

  View details for PubMedID 32454518

• Cross-sectional and longitudinal associations of family income-to-needs ratio with cortical and subcortical brain volume in adolescent boys and girls. Developmental cognitive neuroscience King, L. S., Dennis, E. L., Humphreys, K. L., Thompson, P. M., Gotlib, I. H. 2020; 44: 100796

  Abstract

  Deviations in neurodevelopment may underlie the association between lower childhood socioeconomic status and difficulties in cognitive and socioemotional domains. Most previous investigations of the association between childhood socioeconomic status and brain morphology have used cross-sectional designs with samples that span wide age ranges, occluding effects specific to adolescence. Sex differences in the association between socioeconomic status and neurodevelopment may emerge or intensify during adolescence. In a sample representative of the San Francisco Bay Area, we used whole-brain tensor-based morphometry to examine sex differences in the cross-sectional association between variation in family income-to-needs ratio (INR) and cortical and subcortical gray and white matter volume during early adolescence (ages 9-13 years; N = 147), as well as in the longitudinal association between INR and change in volume from early to later adolescence (ages 11-16 years, N = 109). Biological sex interacted with INR to explain variation in volume in several areas cross-sectionally and longitudinally. Effects were primarily in cortical gray matter areas, including regions of the association cortex and sensorimotor processing areas. Effect sizes tended to be larger in boys than in girls. Biological sex may be an important variable to consider in analyses of the effects of family income on structural neurodevelopment during adolescence.

  View details for DOI 10.1016/j.dcn.2020.100796

  View details for PubMedID 32479375

• Brain aging in major depressive disorder: results from the ENIGMA major depressive disorder working group. Molecular psychiatry Han, L. K., Dinga, R., Hahn, T., Ching, C. R., Eyler, L. T., Aftanas, L., Aghajani, M., Aleman, A., Baune, B. T., Berger, K., Brak, I., Filho, G. B., Carballedo, A., Connolly, C. G., Couvy-Duchesne, B., Cullen, K. R., Dannlowski, U., Davey, C. G., Dima, D., Duran, F. L., Enneking, V., Filimonova, E., Frenzel, S., Frodl, T., Fu, C. H., Godlewska, B. R., Gotlib, I. H., Grabe, H. J., Groenewold, N. A., Grotegerd, D., Gruber, O., Hall, G. B., Harrison, B. J., Hatton, S. N., Hermesdorf, M., Hickie, I. B., Ho, T. C., Hosten, N., Jansen, A., Kahler, C., Kircher, T., Klimes-Dougan, B., Kramer, B., Krug, A., Lagopoulos, J., Leenings, R., MacMaster, F. P., MacQueen, G., McIntosh, A., McLellan, Q., McMahon, K. L., Medland, S. E., Mueller, B. A., Mwangi, B., Osipov, E., Portella, M. J., Pozzi, E., Reneman, L., Repple, J., Rosa, P. G., Sacchet, M. D., Samann, P. G., Schnell, K., Schrantee, A., Simulionyte, E., Soares, J. C., Sommer, J., Stein, D. J., Steinstrater, O., Strike, L. T., Thomopoulos, S. I., van Tol, M., Veer, I. M., Vermeiren, R. R., Walter, H., van der Wee, N. J., van der Werff, S. J., Whalley, H., Winter, N. R., Wittfeld, K., Wright, M. J., Wu, M., Volzke, H., Yang, T. T., Zannias, V., de Zubicaray, G. I., Zunta-Soares, G. B., Abe, C., Alda, M., Andreassen, O. A., Boen, E., Bonnin, C. M., Canales-Rodriguez, E. J., Cannon, D., Caseras, X., Chaim-Avancini, T. M., Elvsashagen, T., Favre, P., Foley, S. F., Fullerton, J. M., Goikolea, J. M., Haarman, B. C., Hajek, T., Henry, C., Houenou, J., Howells, F. M., Ingvar, M., Kuplicki, R., Lafer, B., Landen, M., Machado-Vieira, R., Malt, U. F., McDonald, C., Mitchell, P. B., Nabulsi, L., Otaduy, M. C., Overs, B. J., Polosan, M., Pomarol-Clotet, E., Radua, J., Rive, M. M., Roberts, G., Ruhe, H. G., Salvador, R., Sarro, S., Satterthwaite, T. D., Savitz, J., Schene, A. H., Schofield, P. R., Serpa, M. H., Sim, K., Soeiro-de-Souza, M. G., Sutherland, A. N., Temmingh, H. S., Timmons, G. M., Uhlmann, A., Vieta, E., Wolf, D. H., Zanetti, M. V., Jahanshad, N., Thompson, P. M., Veltman, D. J., Penninx, B. W., Marquand, A. F., Cole, J. H., Schmaal, L. 2020

  Abstract

  Major depressive disorder (MDD) is associated with an increased risk of brain atrophy, aging-related diseases, and mortality. We examined potential advanced brain aging in adult MDD patients, and whether this process is associated with clinical characteristics in a large multicenter international dataset. We performed a mega-analysis by pooling brain measures derived from T1-weighted MRI scans from 19 samples worldwide. Healthy brain aging was estimated by predicting chronological age (18-75 years) from 7 subcortical volumes, 34 cortical thickness and 34 surface area, lateral ventricles and total intracranial volume measures separately in 952 male and 1236 female controls from the ENIGMA MDD working group. The learned model coefficients were applied to 927 male controls and 986 depressed males, and 1199 female controls and 1689 depressed females to obtain independent unbiased brain-based age predictions. The difference between predicted "brain age" and chronological age was calculated to indicate brain-predicted age difference (brain-PAD). On average, MDD patients showed a higher brain-PAD of +1.08 (SE 0.22) years (Cohen's d=0.14, 95% CI: 0.08-0.20) compared with controls. However, this difference did not seem to be driven by specific clinical characteristics (recurrent status, remission status, antidepressant medication use, age of onset, or symptom severity). This highly powered collaborative effort showed subtle patterns of age-related structural brain abnormalities in MDD. Substantial within-group variance and overlap between groups were observed. Longitudinal studies of MDD and somatic health outcomes are needed to further assess the clinical value of these brain-PAD estimates.

  View details for DOI 10.1038/s41380-020-0754-0

  View details for PubMedID 32424236

• Biomarker Trends: Luminex & Olink, Dried Blood Spots & Plasma Rosenberg-Hasson, Y., Ho, T. C., Simon, T. D., Liang, J., Chang, S., Herschmann, I., Gotlib, I. H., Maecker, H. T. AMER ASSOC IMMUNOLOGISTS. 2020

  View details for Web of Science ID 000589972401526

• The Effects of Maternal Depression on Infant White Matter Organization and Social-Emotional Development: A Longitudinal Study Borchers, L., Dennis, E., King, L., Humphreys, K., Gotlib, I. ELSEVIER SCIENCE INC. 2020: S106

  View details for Web of Science ID 000535308200251

• Family Dynamics and Emotion Processing: Functional Connectivity Biomarkers of Risk and Resilience in Youth at Familial Risk for Mood Disorders Fischer, A., Holt-Gosselin, B., Nimarko, A., Carta, K., Kaur, J., Lu, Y., Rodriguez, N., Takada, C., Gotlib, I., Singh, M. ELSEVIER SCIENCE INC. 2020: S288

  View details for Web of Science ID 000535308200705

• Sex differences in the effects of gonadal hormones on white matter microstructure development in adolescence. Developmental cognitive neuroscience Ho, T. C., Colich, N. L., Sisk, L. M., Oskirko, K., Jo, B., Gotlib, I. H. 2020; 42: 100773

  Abstract

  Adolescence is characterized by rapid brain development in white matter (WM) that is attributed in part to surges in gonadal hormones. To date, however, there have been few longitudinal investigations relating changes in gonadal hormones and WM development in adolescents. We acquired diffusion-weighted MRI to estimate mean fractional anisotropy (FA) from 10 WM tracts and salivary testosterone from 51 females and 29 males (ages 9-14 years) who were matched on pubertal stage and followed, on average, for 2 years. We tested whether interactions between sex and changes in testosterone levels significantly explained changes in FA. We found positive associations between changes in testosterone and changes in FA within the corpus callosum, cingulum cingulate, and corticospinal tract in females (all ps<0.05, corrected) and non-significant associations in males. We also collected salivary estradiol from females and found that increases in estradiol were associated with increases in FA in the left uncinate fasciculus (p=0.04, uncorrected); however, this effect was no longer significant after accounting for changes in testosterone. Our findings indicate there are sex differences in how changes in testosterone relate to changes in WM microstructure of tracts that support impulse control and emotion regulation across the pubertal transition.

  View details for DOI 10.1016/j.dcn.2020.100773

  View details for PubMedID 32452463

• Studying the Intergenerational Transmission of Risk for Depression: Current Status and Future Directions. Current directions in psychological science Gotlib, I. H., Goodman, S. H., Humphreys, K. L. 2020; 29 (2): 174-179

  Abstract

  Studying offspring of depressed mothers is a promising strategy for elucidating factors that contribute to depression onset, given that these offspring are three to six times more likely to develop depression than are their low-risk peers. In this paper we briefly describe representative findings from studies of younger and older offspring of depressed mothers and identify factors that have garnered the most consistent empirical support across development. We discuss what these studies can and cannot tell us about mechanisms that might underlie the intergenerational transmission of risk for depression, regardless of the age of offspring being studied. Finally, in light of limitations of this literature, we offer recommendations for future research.

  View details for DOI 10.1177/0963721420901590

  View details for PubMedID 33758474

  View details for PubMedCentralID PMC7983041

• Subcortical shape alterations in major depressive disorder: Findings from the ENIGMA major depressive disorder working group. Human brain mapping Ho, T. C., Gutman, B., Pozzi, E., Grabe, H. J., Hosten, N., Wittfeld, K., Volzke, H., Baune, B., Dannlowski, U., Forster, K., Grotegerd, D., Redlich, R., Jansen, A., Kircher, T., Krug, A., Meinert, S., Nenadic, I., Opel, N., Dinga, R., Veltman, D. J., Schnell, K., Veer, I., Walter, H., Gotlib, I. H., Sacchet, M. D., Aleman, A., Groenewold, N. A., Stein, D. J., Li, M., Walter, M., Ching, C. R., Jahanshad, N., Ragothaman, A., Isaev, D., Zavaliangos-Petropulu, A., Thompson, P. M., Samann, P. G., Schmaal, L. 2020

  Abstract

  Alterations in regional subcortical brain volumes have been investigated as part of the efforts of an international consortium, ENIGMA, to identify reliable neural correlates of major depressive disorder (MDD). Given that subcortical structures are comprised of distinct subfields, we sought to build significantly from prior work by precisely mapping localized MDD-related differences in subcortical regions using shape analysis. In this meta-analysis of subcortical shape from the ENIGMA-MDD working group, we compared 1,781 patients with MDD and 2,953 healthy controls (CTL) on individual measures of shape metrics (thickness and surface area) on the surface of seven bilateral subcortical structures: nucleus accumbens, amygdala, caudate, hippocampus, pallidum, putamen, and thalamus. Harmonized data processing and statistical analyses were conducted locally at each site, and findings were aggregated by meta-analysis. Relative to CTL, patients with adolescent-onset MDD (≤ 21years) had lower thickness and surface area of the subiculum, cornu ammonis (CA) 1 of the hippocampus and basolateral amygdala (Cohen's d =-0.164 to -0.180). Relative to first-episode MDD, recurrent MDD patients had lower thickness and surface area in the CA1 of the hippocampus and the basolateral amygdala (Cohen's d = -0.173 to -0.184). Our results suggest that previously reported MDD-associated volumetric differences may be localized to specific subfields of these structures that have been shown to be sensitive to the effects of stress, with important implications for mapping treatments to patients based on specific neural targets and key clinical features.

  View details for DOI 10.1002/hbm.24988

  View details for PubMedID 32198905

• Associations of waking cortisol with DHEA and testosterone across the pubertal transition: Effects of threat-related early life stress. Psychoneuroendocrinology King, L. S., Graber, M. G., Colich, N. L., Gotlib, I. H. 2020; 115: 104651

  Abstract

  Atypical regulation of the hypothalamic-pituitary-adrenal (HPA) axis is a putative mechanism underlying the association between exposure to early life stress (ELS) and the subsequent development of mental and physical health difficulties. Recent research indicates that puberty is a period of HPA-axis plasticity during which the effects of exposure to ELS on cortisol regulation may change. In particular, increases in the sex hormones that drive pubertal maturation, including dehydroepiandrosterone (DHEA) and testosterone, may be implicated in pubertal recalibration of cortisol regulation. In the current study, we examined the associations among levels of objectively-rated threat-related ELS and salivary waking cortisol, DHEA, and testosterone in a sample of 178 adolescents (55 % female) who were in early puberty at baseline (Tanner stages 1-3; mean Tanner stage[SD] = 1.93[0.64]; mean age[SD] = 11.42[1.04]) and were followed up approximately two years later (mean Tanner stage[SD] = 3.46[0.86]; mean age[SD] = 13.38[1.06]). Using multi-level modeling, we disaggregated the effects of between-individual levels and within-individual increases in pubertal stage and sex hormones on change in cortisol. Controlling for between-individual differences in average pubertal stage, the association between levels of cortisol and DHEA was more strongly positive among adolescents who evidenced greater within-individual increases in pubertal stage across time. Both higher average levels and greater within-individual increases in DHEA and testosterone were associated with increases in cortisol across time, indicating positive coupling of developmental changes in these hormones; however, coupling was attenuated in adolescents who were exposed to more severe threat-related ELS prior to puberty. These findings advance our understanding of the development of the HPA-axis and its association with childhood environmental risk during puberty.

  View details for DOI 10.1016/j.psyneuen.2020.104651

  View details for PubMedID 32199287

• The human connectome project for disordered emotional states: Protocol and rationale for a research domain criteria study of brain connectivity in young adult anxiety and depression. NeuroImage Tozzi, L., Staveland, B., Holt-Gosselin, B., Chesnut, M., Chang, S. E., Choi, D., Shiner, M. L., Wu, H., Lerma-Usabiaga, G., Sporns, O., Barch, D., Gotlib, I. H., Hastie, T. J., Kerr, A. B., Poldrack, R. A., Wandell, B. A., Wintermark, M., Williams, L. M. 2020: 116715

  Abstract

  Through the Human Connectome Project (HCP) our understanding of the functional connectome of the healthy brain has been dramatically accelerated. Given the pressing public health need, we must increase our understanding of how connectome dysfunctions give rise to disordered mental states. Mental disorders arising from high levels of negative emotion or from the loss of positive emotional experience affect over 400 million people globally. Such states of disordered emotion cut across multiple diagnostic categories of mood and anxiety disorders and are compounded by accompanying disruptions in cognitive function. Not surprisingly, these forms of psychopathology are the leading cause of disability worldwide. The Research Domain Criteria (RDoC) initiative spearheaded by NIMH offers a framework for characterizing the relations among connectome dysfunctions, anchored in neural circuits and phenotypic profiles of behavior and self-reported symptoms. Here, we report on our Connectomes Related to Human Disease protocol for integrating an RDoC framework with HCP protocols to characterize connectome dysfunctions in disordered emotional states, and present quality control data from a representative sample of participants. We focus on three RDoC domains and constructs most relevant to depression and anxiety: 1) loss and acute threat within the Negative Valence System (NVS) domain; 2) reward valuation and responsiveness within the Positive Valence System (PVS) domain; and 3) working memory and cognitive control within the Cognitive System (CS) domain. For 29 healthy controls, we present preliminary imaging data: functional magnetic resonance imaging collected in the resting state and in tasks matching our constructs of interest ("Emotion", "Gambling" and "Continuous Performance" tasks), as well as diffusion-weighted imaging. All functional scans demonstrated good signal-to-noise ratio. Established neural networks were robustly identified in the resting state condition by independent component analysis. Processing of negative emotional faces significantly activated the bilateral dorsolateral prefrontal and occipital cortices, fusiform gyrus and amygdalae. Reward elicited a response in the bilateral dorsolateral prefrontal, parietal and occipital cortices, and in the striatum. Working memory was associated with activation in the dorsolateral prefrontal, parietal, motor, temporal and insular cortices, in the striatum and cerebellum. Diffusion tractography showed consistent profiles of fractional anisotropy along known white matter tracts. We also show that results are comparable to those in a matched sample from the HCP Healthy Young Adult data release. These preliminary data provide the foundation for acquisition of 250 subjects who are experiencing disordered emotional states. When complete, these data will be used to develop a neurobiological model that maps connectome dysfunctions to specific behaviors and symptoms.

  View details for DOI 10.1016/j.neuroimage.2020.116715

  View details for PubMedID 32147367

• Studying the Intergenerational Transmission of Risk for Depression: Current Status and Future Directions CURRENT DIRECTIONS IN PSYCHOLOGICAL SCIENCE Gotlib, I. H., Goodman, S. H., Humphreys, K. L. 2020

  View details for DOI 10.1177/0963721420901590

  View details for Web of Science ID 000515461700001

• Child maltreatment and depression: A meta-analysis of studies using the Childhood Trauma Questionnaire. Child abuse & neglect Humphreys, K. L., LeMoult, J., Wear, J. G., Piersiak, H. A., Lee, A., Gotlib, I. H. 2020; 102: 104361

  Abstract

  BACKGROUND: Researchers have documented that child maltreatment is associated with adverse long-term consequences for mental health, including increased risk for depression. Attempts to conduct meta-analyses of the association between different forms of child maltreatment and depressive symptomatology in adulthood, however, have been limited by the wide range of definitions of child maltreatment in the literature.OBJECTIVE: We sought to meta-analyze a single, widely-used dimensional measure of child maltreatment, the Childhood Trauma Questionnaire, with respect to depression diagnosis and symptom scores.PARTICIPANTS AND SETTING: 192 unique samples consisting of 68,830 individuals.METHODS: We explored the association between total scores and scores from specific forms of child maltreatment (i.e., emotional abuse, physical abuse, sexual abuse, emotional neglect, and physical neglect) and depression using a random-effects meta-analysis.RESULTS: We found that higher child maltreatment scores were associated with a diagnosis of depression (g = 1.07; 95 % CI, 0.95-1.19) and with higher depression symptom scores (Z = .35; 95 % CI, .32-.38). Moreover, although each type of child maltreatment was positively associated with depression diagnosis and scores, there was variability in the size of the effects, with emotional abuse and emotional neglect demonstrating the strongest associations.CONCLUSIONS: These analyses provide important evidence of the link between child maltreatment and depression, and highlight the particularly larger association with emotional maltreatment in childhood.

  View details for DOI 10.1016/j.chiabu.2020.104361

  View details for PubMedID 32062423

• Epigenetic signatures of attachment insecurity and childhood adversity provide evidence for role transition in the pathogenesis of perinatal depression. Translational psychiatry Robakis, T. K., Zhang, S., Rasgon, N. L., Li, T., Wang, T., Roth, M. C., Humphreys, K. L., Gotlib, I. H., Ho, M., Khechaduri, A., Watson, K., Roat-Shumway, S., Budhan, V. V., Davis, K. N., Crowe, S. D., Ellie Williams, K., Urban, A. E. 2020; 10 (1): 48

  Abstract

  Early life adversity and insecure attachment style are known risk factors for perinatal depression. The biological pathways linking these experiences, however, have not yet been elucidated. We hypothesized that overlap in patterns of DNA methylation in association with each of these phenomena could identify genes and pathways of importance. Specifically, we wished to distinguish between allostatic-load and role-transition hypotheses of perinatal depression. We conducted a large-scale analysis of methylation patterns across 5*106 individual CG dinucleotides in 54 women participating in a longitudinal prospective study of perinatal depression, using clustering-based criteria for significance to control for multiple comparisons. We identified 1580 regions in which methylation density was associated with childhood adversity, 3 in which methylation density was associated with insecure attachment style, and 6 in which methylation density was associated with perinatal depression. Shorter telomeres were observed in association with childhood trauma but not with perinatal depression or attachment insecurity. A detailed analysis of methylation density in the oxytocin receptor gene revealed similar patterns of DNA methylation in association with perinatal depression and with insecure attachment style, while childhood trauma was associated with a distinct methylation pattern in this gene. Clinically, attachment style was strongly associated with depression only in pregnancy and the early postpartum, whereas the association of childhood adversity with depression was time-invariant. We concluded that the broad DNA methylation signature and reduced telomere length associated with childhood adversity could indicate increased allostatic load across multiple body systems, whereas perinatal depression and attachment insecurity may be narrower phenotypes with more limited DNA methylation signatures outside the CNS, and no apparent association with telomere length or, by extension, allostatic load. In contrast, the finding of matching DNA methylation patterns within the oxytocin receptor gene for perinatal depression and attachment insecurity is consistent with the theory that the perinatal period is a time of activation of existing attachment schemas for the purpose of structuring the mother-child relationship, and that such activation may occur in part through specific patterns of methylation of the oxytocin receptor gene.

  View details for DOI 10.1038/s41398-020-0703-3

  View details for PubMedID 32066670

• The role of affective control in emotion regulation during adolescence. Emotion (Washington, D.C.) Schweizer, S., Gotlib, I. H., Blakemore, S. 2020; 20 (1): 80–86

  Abstract

  In this review, we evaluate evidence for the hypothesis that developmental changes in emotion regulation tendencies during adolescence depend on the maturation of affective control. Affective control refers to the application of cognitive control to affective contexts, that is, the capacity to attend and respond to goal-relevant affective information, while inhibiting attention and responses toward distracting affective information. The evidence suggests that affective control develops throughout adolescence into adulthood. However, the developmental trajectory appears not to be uniform across different facets of affective control. In particular, the capacity to inhibit attention and responses to distracting affective information may be reduced during adolescence relative to childhood and adulthood. Focusing on the association between affective control and emotion regulation development in adolescence, the research reviewed supports the notion of affective control as a cognitive building block of successful emotion regulation. Good affective control appears related to fewer ruminative tendencies in adolescence as well as more frequent and successful reappraisal in older adolescents. Lower use of habitual suppression, itself a type of affective inhibition, shows an association with updating capacity. We conclude by discussing the implications of these findings for mental health and the potential mental health benefits associated with improving affective control. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

  View details for DOI 10.1037/emo0000695

  View details for PubMedID 31961183

• Effects of working memory training on cognitive, affective, and biological responses to stress in major depression: A novel cognitive bias modification protocol. Journal of affective disorders Jopling, E., Gotlib, I. H., LeMoult, J. 2020; 265: 45–51

  Abstract

  BACKGROUND: Over 320 million individuals are living with Major Depressive Disorder (MDD), a leading cause of disability worldwide. Thus, there is a crucial need to identify processes that contribute to the maintenance of depressive episodes. Difficulty removing negative information from working memory (WM) is posited to exacerbate affective, cognitive, and biological dysregulation in Major Depressive Disorder (MDD), but this has not yet been tested empirically.METHODS: In this study we examined whether training depressed individuals to remove negative information from WM (RNI training) would reduce symptoms of depression and levels of rumination, and would be associated with attenuated biological responsivity to stress. Individuals diagnosed with MDD were randomly assigned to complete Real-RNI training or Sham-RNI training for six days.RESULTS: Across conditions, participants exhibited significant improvements from pre- to post-training in removing negative information from WM, symptoms of depression, and rumination. Furthermore, participants in the Real-RNI condition showed a more attenuated pattern of cortisol and respiratory sinus arrhythmia (RSA) responses to stress than did participants in the Sham-RNI training condition.LIMITATIONS: We did not assess the long-term effects of training. It will be important for future research to examine whether the documented training-related effects persist across time.CONCLUSIONS: This study is the first to examine the effects of RNI training on clinical symptoms and biological responses to stress in MDD, and it provides experimental evidence that training individuals with depression to remove negative information from WM can help to modulate the heightened biological responses to stress seen in depression.

  View details for DOI 10.1016/j.jad.2020.01.007

  View details for PubMedID 31957691

• Water contaminant levels interact with parenting environment to predict development of depressive symptoms in adolescents DEVELOPMENTAL SCIENCE Manczak, E. M., Miller, J. G., Gotlib, I. H. 2020; 23 (1)

  View details for DOI 10.1111/desc.12838

  View details for Web of Science ID 000501321400020

• Maternal Depression in Early Childhood and Developmental Vulnerability at School Entry. Pediatrics Wall-Wieler, E. n., Roos, L. L., Gotlib, I. H. 2020

  Abstract

  To assess the relation between exposure to maternal depression before age 5 and 5 domains of developmental vulnerability at school entry, overall, and by age at exposure.This cohort study included all children born in Manitoba, Canada, who completed the Early Development Instrument between 2005 and 2016 (N = 52 103). Maternal depression was defined by using physician visits, hospitalizations, and pharmaceutical data; developmental vulnerability was assessed by using the Early Development Instrument. Relative risk of developmental vulnerability was assessed by using log-binomial regression models adjusted for characteristics at birth.Children exposed to maternal depression before age 5 had a 17% higher risk of having at least 1 developmental vulnerability at school entry than did children not exposed to maternal depression before age 5. Exposure to maternal depression was most strongly associated with difficulties in social competence (adjusted relative risk [aRR] = 1.28; 95% confidence interval [CI]: 1.20-1.38), physical health and well-being (aRR = 1.28; 95% CI: 1.20-1.36), and emotional maturity (aRR = 1.27; 95% CI: 1.18-1.37). For most developmental domains, exposure to maternal depression before age 1 and between ages 4 and 5 had the strongest association with developmental vulnerability.Our finding that children exposed to maternal depression are at higher risk for developmental vulnerability at school entry is consistent with previous findings. We extended this literature by documenting that the adverse effects of exposure to maternal depression are specific to particular developmental domains and that these effects vary depending on the age at which the child is exposed to maternal depression.

  View details for DOI 10.1542/peds.2020-0794

  View details for PubMedID 32817440

• Virtual Histology of Cortical Thickness and Shared Neurobiology in 6 Psychiatric Disorders. JAMA psychiatry Patel, Y. n., Parker, N. n., Shin, J. n., Howard, D. n., French, L. n., Thomopoulos, S. I., Pozzi, E. n., Abe, Y. n., Abé, C. n., Anticevic, A. n., Alda, M. n., Aleman, A. n., Alloza, C. n., Alonso-Lana, S. n., Ameis, S. H., Anagnostou, E. n., McIntosh, A. A., Arango, C. n., Arnold, P. D., Asherson, P. n., Assogna, F. n., Auzias, G. n., Ayesa-Arriola, R. n., Bakker, G. n., Banaj, N. n., Banaschewski, T. n., Bandeira, C. E., Baranov, A. n., Bargalló, N. n., Bau, C. H., Baumeister, S. n., Baune, B. T., Bellgrove, M. A., Benedetti, F. n., Bertolino, A. n., Boedhoe, P. S., Boks, M. n., Bollettini, I. n., Del Mar Bonnin, C. n., Borgers, T. n., Borgwardt, S. n., Brandeis, D. n., Brennan, B. P., Bruggemann, J. M., Bülow, R. n., Busatto, G. F., Calderoni, S. n., Calhoun, V. D., Calvo, R. n., Canales-Rodríguez, E. J., Cannon, D. M., Carr, V. J., Cascella, N. n., Cercignani, M. n., Chaim-Avancini, T. M., Christakou, A. n., Coghill, D. n., Conzelmann, A. n., Crespo-Facorro, B. n., Cubillo, A. I., Cullen, K. R., Cupertino, R. B., Daly, E. n., Dannlowski, U. n., Davey, C. G., Denys, D. n., Deruelle, C. n., Di Giorgio, A. n., Dickie, E. W., Dima, D. n., Dohm, K. n., Ehrlich, S. n., Ely, B. A., Erwin-Grabner, T. n., Ethofer, T. n., Fair, D. A., Fallgatter, A. J., Faraone, S. V., Fatjó-Vilas, M. n., Fedor, J. M., Fitzgerald, K. D., Ford, J. M., Frodl, T. n., Fu, C. H., Fullerton, J. M., Gabel, M. C., Glahn, D. C., Roberts, G. n., Gogberashvili, T. n., Goikolea, J. M., Gotlib, I. H., Goya-Maldonado, R. n., Grabe, H. J., Green, M. J., Grevet, E. H., Groenewold, N. A., Grotegerd, D. n., Gruber, O. n., Gruner, P. n., Guerrero-Pedraza, A. n., Gur, R. E., Gur, R. C., Haar, S. n., Haarman, B. C., Haavik, J. n., Hahn, T. n., Hajek, T. n., Harrison, B. J., Harrison, N. A., Hartman, C. A., Whalley, H. C., Heslenfeld, D. J., Hibar, D. P., Hilland, E. n., Hirano, Y. n., Ho, T. C., Hoekstra, P. J., Hoekstra, L. n., Hohmann, S. n., Hong, L. E., Höschl, C. n., Høvik, M. F., Howells, F. M., Nenadic, I. n., Jalbrzikowski, M. n., James, A. C., Janssen, J. n., Jaspers-Fayer, F. n., Xu, J. n., Jonassen, R. n., Karkashadze, G. n., King, J. A., Kircher, T. n., Kirschner, M. n., Koch, K. n., Kochunov, P. n., Kohls, G. n., Konrad, K. n., Krämer, B. n., Krug, A. n., Kuntsi, J. n., Kwon, J. S., Landén, M. n., Landrø, N. I., Lazaro, L. n., Lebedeva, I. S., Leehr, E. J., Lera-Miguel, S. n., Lesch, K. P., Lochner, C. n., Louza, M. R., Luna, B. n., Lundervold, A. J., MacMaster, F. P., Maglanoc, L. A., Malpas, C. B., Portella, M. J., Marsh, R. n., Martyn, F. M., Mataix-Cols, D. n., Mathalon, D. H., McCarthy, H. n., McDonald, C. n., McPhilemey, G. n., Meinert, S. n., Menchón, J. M., Minuzzi, L. n., Mitchell, P. B., Moreno, C. n., Morgado, P. n., Muratori, F. n., Murphy, C. M., Murphy, D. n., Mwangi, B. n., Nabulsi, L. n., Nakagawa, A. n., Nakamae, T. n., Namazova, L. n., Narayanaswamy, J. n., Jahanshad, N. n., Nguyen, D. D., Nicolau, R. n., O'Gorman Tuura, R. L., O'Hearn, K. n., Oosterlaan, J. n., Opel, N. n., Ophoff, R. A., Oranje, B. n., García de la Foz, V. O., Overs, B. J., Paloyelis, Y. n., Pantelis, C. n., Parellada, M. n., Pauli, P. n., Picó-Pérez, M. n., Picon, F. A., Piras, F. n., Piras, F. n., Plessen, K. J., Pomarol-Clotet, E. n., Preda, A. n., Puig, O. n., Quidé, Y. n., Radua, J. n., Ramos-Quiroga, J. A., Rasser, P. E., Rauer, L. n., Reddy, J. n., Redlich, R. n., Reif, A. n., Reneman, L. n., Repple, J. n., Retico, A. n., Richarte, V. n., Richter, A. n., Rosa, P. G., Rubia, K. K., Hashimoto, R. n., Sacchet, M. D., Salvador, R. n., Santonja, J. n., Sarink, K. n., Sarró, S. n., Satterthwaite, T. D., Sawa, A. n., Schall, U. n., Schofield, P. R., Schrantee, A. n., Seitz, J. n., Serpa, M. H., Setién-Suero, E. n., Shaw, P. n., Shook, D. n., Silk, T. J., Sim, K. n., Simon, S. n., Simpson, H. B., Singh, A. n., Skoch, A. n., Skokauskas, N. n., Soares, J. C., Soreni, N. n., Soriano-Mas, C. n., Spalletta, G. n., Spaniel, F. n., Lawrie, S. M., Stern, E. R., Stewart, S. E., Takayanagi, Y. n., Temmingh, H. S., Tolin, D. F., Tomecek, D. n., Tordesillas-Gutiérrez, D. n., Tosetti, M. n., Uhlmann, A. n., van Amelsvoort, T. n., van der Wee, N. J., van der Werff, S. J., van Haren, N. E., van Wingen, G. A., Vance, A. n., Vázquez-Bourgon, J. n., Vecchio, D. n., Venkatasubramanian, G. n., Vieta, E. n., Vilarroya, O. n., Vives-Gilabert, Y. n., Voineskos, A. N., Völzke, H. n., von Polier, G. G., Walton, E. n., Weickert, T. W., Weickert, C. S., Weideman, A. S., Wittfeld, K. n., Wolf, D. H., Wu, M. J., Yang, T. T., Yang, K. n., Yoncheva, Y. n., Yun, J. Y., Cheng, Y. n., Zanetti, M. V., Ziegler, G. C., Franke, B. n., Hoogman, M. n., Buitelaar, J. K., van Rooij, D. n., Andreassen, O. A., Ching, C. R., Veltman, D. J., Schmaal, L. n., Stein, D. J., van den Heuvel, O. A., Turner, J. A., van Erp, T. G., Pausova, Z. n., Thompson, P. M., Paus, T. n. 2020

  Abstract

  Large-scale neuroimaging studies have revealed group differences in cortical thickness across many psychiatric disorders. The underlying neurobiology behind these differences is not well understood.To determine neurobiologic correlates of group differences in cortical thickness between cases and controls in 6 disorders: attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BD), major depressive disorder (MDD), obsessive-compulsive disorder (OCD), and schizophrenia.Profiles of group differences in cortical thickness between cases and controls were generated using T1-weighted magnetic resonance images. Similarity between interregional profiles of cell-specific gene expression and those in the group differences in cortical thickness were investigated in each disorder. Next, principal component analysis was used to reveal a shared profile of group difference in thickness across the disorders. Analysis for gene coexpression, clustering, and enrichment for genes associated with these disorders were conducted. Data analysis was conducted between June and December 2019. The analysis included 145 cohorts across 6 psychiatric disorders drawn from the ENIGMA consortium. The numbers of cases and controls in each of the 6 disorders were as follows: ADHD: 1814 and 1602; ASD: 1748 and 1770; BD: 1547 and 3405; MDD: 2658 and 3572; OCD: 2266 and 2007; and schizophrenia: 2688 and 3244.Interregional profiles of group difference in cortical thickness between cases and controls.A total of 12 721 cases and 15 600 controls, ranging from ages 2 to 89 years, were included in this study. Interregional profiles of group differences in cortical thickness for each of the 6 psychiatric disorders were associated with profiles of gene expression specific to pyramidal (CA1) cells, astrocytes (except for BD), and microglia (except for OCD); collectively, gene-expression profiles of the 3 cell types explain between 25% and 54% of variance in interregional profiles of group differences in cortical thickness. Principal component analysis revealed a shared profile of difference in cortical thickness across the 6 disorders (48% variance explained); interregional profile of this principal component 1 was associated with that of the pyramidal-cell gene expression (explaining 56% of interregional variation). Coexpression analyses of these genes revealed 2 clusters: (1) a prenatal cluster enriched with genes involved in neurodevelopmental (axon guidance) processes and (2) a postnatal cluster enriched with genes involved in synaptic activity and plasticity-related processes. These clusters were enriched with genes associated with all 6 psychiatric disorders.In this study, shared neurobiologic processes were associated with differences in cortical thickness across multiple psychiatric disorders. These processes implicate a common role of prenatal development and postnatal functioning of the cerebral cortex in these disorders.

  View details for DOI 10.1001/jamapsychiatry.2020.2694

  View details for PubMedID 32857118

• Greater age-related changes in white matter morphometry following early life stress: Associations with internalizing problems in adolescence. Developmental cognitive neuroscience Chahal, R. n., Kirshenbaum, J. S., Ho, T. C., Mastrovito, D. n., Gotlib, I. H. 2020; 47: 100899

  Abstract

  Early life stress (ELS) is associated with increased risk for internalizing disorders and variations in gray matter development. It is unclear, however, whether ELS affects normative age-related changes in white matter (WM) morphology, and if such maturational differences are associated with risk for internalizing psychopathology. We conducted comprehensive interviews in a cross-sectional sample of young adolescents (N = 156; 89 F; Ages 9-14) to assess lifetime exposure to stress and objective cumulative ELS severity. We used diffusion-weighted imaging to measure WM fixel-based morphometry and tested the effects of age and ELS on WM fiber density and cross-section (FDC), and associations between WM FDC and internalizing problems. Age was positively associated with FDC in all WM tracts; greater ELS severity was related to stronger age-WM associations in several association tracts connecting the frontal lobes with limbic, parietal, and occipital regions, including bilateral superior and inferior longitudinal and uncinate fasciculi (UF). Among older adolescents with greater ELS severity, a higher UF FDC was associated with fewer internalizing problems. Greater ELS severity predicted more mature WM morphometry in tracts implicated in emotion regulation and cognitive processing. More phenotypically mature UF WM may be adaptive against internalizing psychopathology in adolescents exposed to ELS.

  View details for DOI 10.1016/j.dcn.2020.100899

  View details for PubMedID 33340790

• Distinctions between sex and time in patterns of DNA methylation across puberty. BMC genomics Moore, S. R., Humphreys, K. L., Colich, N. L., Davis, E. G., Lin, D. T., MacIsaac, J. L., Kobor, M. S., Gotlib, I. H. 2020; 21 (1): 389

  Abstract

  There are significant sex differences in human physiology and disease; the genomic sources of these differences, however, are not well understood. During puberty, a drastic neuroendocrine shift signals physical changes resulting in robust sex differences in human physiology. Here, we explore how shifting patterns of DNA methylation may inform these pathways of biological plasticity during the pubertal transition. In this study we analyzed DNA methylation (DNAm) in saliva at two time points across the pubertal transition within the same individuals. Our purpose was to compare two domains of DNAm patterns that may inform processes of sexual differentiation 1) sex related sites, which demonstrated differences between males from females and 2) time related sites in which DNAm shifted significantly between timepoints. We further explored the correlated network structure sex and time related DNAm networks and linked these patterns to pubertal stage, assays of salivary testosterone, a reliable diagnostic of free, unbound hormone that is available to act on target tissues, and overlap with androgen response elements.Sites that differed by biological sex were largely independent of sites that underwent change across puberty. Time-related DNAm sites, but not sex-related sites, formed correlated networks that were associated with pubertal stage. Both time and sex DNAm networks reflected salivary testosterone levels that were enriched for androgen response elements, with sex-related DNAm networks being informative of testosterone levels above and beyond biological sex later in the pubertal transition.These results inform our understanding of the distinction between sex- and time-related differences in DNAm during the critical period of puberty and highlight a novel linkage between correlated patterns of sex-related DNAm and levels of salivary testosterone.

  View details for DOI 10.1186/s12864-020-06789-3

  View details for PubMedID 32493224

• Greater male than female variability in regional brain structure across the lifespan. Human brain mapping Wierenga, L. M., Doucet, G. E., Dima, D. n., Agartz, I. n., Aghajani, M. n., Akudjedu, T. N., Albajes-Eizagirre, A. n., Alnaes, D. n., Alpert, K. I., Andreassen, O. A., Anticevic, A. n., Asherson, P. n., Banaschewski, T. n., Bargallo, N. n., Baumeister, S. n., Baur-Streubel, R. n., Bertolino, A. n., Bonvino, A. n., Boomsma, D. I., Borgwardt, S. n., Bourque, J. n., den Braber, A. n., Brandeis, D. n., Breier, A. n., Brodaty, H. n., Brouwer, R. M., Buitelaar, J. K., Busatto, G. F., Calhoun, V. D., Canales-Rodríguez, E. J., Cannon, D. M., Caseras, X. n., Castellanos, F. X., Chaim-Avancini, T. M., Ching, C. R., Clark, V. P., Conrod, P. J., Conzelmann, A. n., Crivello, F. n., Davey, C. G., Dickie, E. W., Ehrlich, S. n., Van't Ent, D. n., Fisher, S. E., Fouche, J. P., Franke, B. n., Fuentes-Claramonte, P. n., de Geus, E. J., Giorgio, A. D., Glahn, D. C., Gotlib, I. H., Grabe, H. J., Gruber, O. n., Gruner, P. n., Gur, R. E., Gur, R. C., Gurholt, T. P., de Haan, L. n., Haatveit, B. n., Harrison, B. J., Hartman, C. A., Hatton, S. N., Heslenfeld, D. J., van den Heuvel, O. A., Hickie, I. B., Hoekstra, P. J., Hohmann, S. n., Holmes, A. J., Hoogman, M. n., Hosten, N. n., Howells, F. M., Hulshoff Pol, H. E., Huyser, C. n., Jahanshad, N. n., James, A. C., Jiang, J. n., Jönsson, E. G., Joska, J. A., Kalnin, A. J., Klein, M. n., Koenders, L. n., Kolskår, K. K., Krämer, B. n., Kuntsi, J. n., Lagopoulos, J. n., Lazaro, L. n., Lebedeva, I. S., Lee, P. H., Lochner, C. n., Machielsen, M. W., Maingault, S. n., Martin, N. G., Martínez-Zalacaín, I. n., Mataix-Cols, D. n., Mazoyer, B. n., McDonald, B. C., McDonald, C. n., McIntosh, A. M., McMahon, K. L., McPhilemy, G. n., van der Meer, D. n., Menchón, J. M., Naaijen, J. n., Nyberg, L. n., Oosterlaan, J. n., Paloyelis, Y. n., Pauli, P. n., Pergola, G. n., Pomarol-Clotet, E. n., Portella, M. J., Radua, J. n., Reif, A. n., Richard, G. n., Roffman, J. L., Rosa, P. G., Sacchet, M. D., Sachdev, P. S., Salvador, R. n., Sarró, S. n., Satterthwaite, T. D., Saykin, A. J., Serpa, M. H., Sim, K. n., Simmons, A. n., Smoller, J. W., Sommer, I. E., Soriano-Mas, C. n., Stein, D. J., Strike, L. T., Szeszko, P. R., Temmingh, H. S., Thomopoulos, S. I., Tomyshev, A. S., Trollor, J. N., Uhlmann, A. n., Veer, I. M., Veltman, D. J., Voineskos, A. n., Völzke, H. n., Walter, H. n., Wang, L. n., Wang, Y. n., Weber, B. n., Wen, W. n., West, J. D., Westlye, L. T., Whalley, H. C., Williams, S. C., Wittfeld, K. n., Wolf, D. H., Wright, M. J., Yoncheva, Y. N., Zanetti, M. V., Ziegler, G. C., de Zubicaray, G. I., Thompson, P. M., Crone, E. A., Frangou, S. n., Tamnes, C. K. 2020

  Abstract

  For many traits, males show greater variability than females, with possible implications for understanding sex differences in health and disease. Here, the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Consortium presents the largest-ever mega-analysis of sex differences in variability of brain structure, based on international data spanning nine decades of life. Subcortical volumes, cortical surface area and cortical thickness were assessed in MRI data of 16,683 healthy individuals 1-90 years old (47% females). We observed significant patterns of greater male than female between-subject variance for all subcortical volumetric measures, all cortical surface area measures, and 60% of cortical thickness measures. This pattern was stable across the lifespan for 50% of the subcortical structures, 70% of the regional area measures, and nearly all regions for thickness. Our findings that these sex differences are present in childhood implicate early life genetic or gene-environment interaction mechanisms. The findings highlight the importance of individual differences within the sexes, that may underpin sex-specific vulnerability to disorders.

  View details for DOI 10.1002/hbm.25204

  View details for PubMedID 33044802

• Smaller caudate gray matter volume is associated with greater implicit suicidal ideation in depressed adolescents. Journal of affective disorders Ho, T. C., Teresi, G. I., Ojha, A. n., Walker, J. C., Kirshenbaum, J. S., Singh, M. K., Gotlib, I. H. 2020; 278: 650–57

  Abstract

  Objective biomarkers of cognitive vulnerabilities related to suicidal ideation (SI) may assist in early prevention in adolescents. Previously, we found that smaller gray matter volumes (GMVs) of the dorsal striatum prospectively predicted implicit SI, measured using a computerized implicit association test (IAT) assessing associations between "self" and "death," in a community sample of adolescents. Here, we sought to replicate these findings in an independent sample of depressed adolescents.53 depressed adolescents who varied in severity of suicidal thoughts and behaviors completed high-resolution structural MRI. Caudate, putamen, and nucleus accumbens GMVs were estimated using FreeSurfer 6.0. Robust linear regressions were used to examine associations between striatal GMVs and implicit and explicit SI, covarying for sex, age, total intracranial volume, medication use, and depression severity. Significance was determined using Bonferroni correction. Finally, LASSO regression was used to identify which striatal GMV contributed most to prediction of implicit SI.Smaller bilateral caudate and right nucleus accumbens GMVs were associated with higher IAT scores (all ps<0.001). Smaller putamen and nucleus accumbens GMVs were not associated with implicit or explicit SI. Our LASSO analysis indicated that right caudate GMV contributed most to the prediction of IAT scores.This study is the first to demonstrate that caudate GMVs are significantly associated with implicit self-associations with death in a sample of depressed adolescents. When considered with our previous work, smaller caudate GMVs may be a robust biomarker of implicit SI in adolescents, with clinical implications for early identification of youth at risk for engaging in suicidal behaviors.

  View details for DOI 10.1016/j.jad.2020.09.046

  View details for PubMedID 33039875

• Higher Executive Control Network Coherence Buffers Against Puberty-Related Increases in Internalizing Symptoms During the COVID-19 Pandemic. Biological psychiatry. Cognitive neuroscience and neuroimaging Chahal, R. n., Kirshenbaum, J. S., Miller, J. G., Ho, T. C., Gotlib, I. H. 2020

  Abstract

  Early pubertal maturation has been posited to be a biopsychosocial risk factor for the onset of internalizing psychopathology in adolescence; further, early-maturing youths exhibit heightened reactivity to stressful events. School closures and enforced social distancing, as well as health and financial uncertainties, during the COVID-19 pandemic are expected to adversely affect mental health in youths, particularly adolescents who are already at risk for experiencing emotional difficulties. The executive control network (ECN) supports cognitive processes required to successfully navigate novel challenges and regulate emotions in stressful contexts.We examined whether functional coherence of the ECN, measured using resting-state functional magnetic resonance imaging 5 years before the pandemic (T1), is a neurobiological marker of resilience to increases in the severity of internalizing symptoms during COVID-19 in adolescents who were in more advanced stages of puberty at T1 relative to their same-age peers (N = 85, 49 female).On average, participants reported an increase in symptoms from the 3 months before pandemic to the 2 most recent weeks during the pandemic. We found that early-maturing youths exhibited greater increases in internalizing symptoms during the pandemic if their ECN coherence was low; in contrast, relative pubertal stage was not associated with changes in internalizing symptoms in adolescents with higher ECN coherence at T1.These findings highlight the role of the functional architecture of the brain that supports executive functioning in protecting against risk factors that may exacerbate symptoms of internalizing psychopathology during periods of stress and uncertainty.

  View details for DOI 10.1016/j.bpsc.2020.08.010

  View details for PubMedID 33097469

• Sex Differences in Pubertal Associations with Fronto-accumbal White Matter Morphometry: Implications for Understanding Sensitivity to Reward and Punishment NeuroImage Chahal, R., Delevich, K., Kirshenbaum, J. S., Borchers, L. R., Ho, T. C., Gotlib, I. H. 2020

  View details for DOI 10.1016/j.neuroimage.2020.117598

• Functional neuroimaging biomarkers of resilience in major depressive disorder. Current opinion in psychiatry Fischer, A. S., Hagan, K. E., Gotlib, I. H. 2020

  Abstract

  In this review, we provide an overview of definitions and determinants of resilience in the context of neuroimaging research in major depressive disorder (MDD). We summarize emerging literature on functional neuroimaging biomarkers of resilience in MDD and discuss their clinical relevance and implications for future research.Resilience in MDD is characterized by dissociable profiles of activation and functional connectivity within brain networks involved in cognitive control, emotion regulation, and reward processing. Increased activation of frontal cortical brain regions implicated in cognitive appraisal and emotion regulation is a common characteristic of resilient individuals at high risk for MDD and of individuals with MDD with a favorable illness course. Furthermore, significant associations between fronto-striato-limbic functional connectivity and both positively interpreted stressful life events in resilient high-risk individuals and a favorable response to first-line treatments in depressed individuals suggest that neuro-compensatory changes and experience-dependent plasticity underlie resilience in MDD.Emerging research has identified putative functional neuroimaging biomarkers of resilience in MDD. A continued focus on identifying neurobiological underpinnings of resilience, in the context of dynamic environmental and developmental influences on MDD, will advance our understanding of resilience in this disorder and improve approaches to prevention and treatment.

  View details for DOI 10.1097/YCO.0000000000000662

  View details for PubMedID 33027183

• Early Life Stress, Frontoamygdala Connectivity, and Biological Aging in Adolescence: A Longitudinal Investigation. Cerebral cortex (New York, N.Y. : 1991) Miller, J. G., Ho, T. C., Humphreys, K. L., King, L. S., Foland-Ross, L. C., Colich, N. L., Ordaz, S. J., Lin, J. n., Gotlib, I. H. 2020

  Abstract

  Early life stress (ELS) may accelerate frontoamygdala development related to socioemotional processing, serving as a potential source of resilience. Whether this circuit is associated with other proposed measures of accelerated development is unknown. In a sample of young adolescents, we examined the relations among ELS, frontoamygdala circuitry during viewing of emotional faces, cellular aging as measured by telomere shortening, and pubertal tempo. We found that greater cumulative severity of ELS was associated with stronger negative coupling between bilateral centromedial amygdala and the ventromedial prefrontal cortex, a pattern that may reflect more mature connectivity. More negative frontoamygdala coupling (for distinct amygdala subdivisions) was associated with slower telomere shortening and pubertal tempo over 2 years. These potentially protective associations of negative frontoamygdala connectivity were most pronounced in adolescents who had been exposed to higher ELS. Our findings provide support for the formulation that ELS accelerates maturation of frontoamygdala connectivity and provide novel evidence that this neural circuitry confers protection against accelerated biological aging, particularly for adolescents who have experienced higher ELS. Although negative frontoamygdala connectivity may be an adaptation to ELS, frontoamygdala connectivity, cellular aging, and pubertal tempo do not appear to be measures of the same developmental process.

  View details for DOI 10.1093/cercor/bhaa057

  View details for PubMedID 32215605

• Brain network connectivity and the heterogeneity of depression in adolescence: A precision mental health perspective Journal of Child Psychology and Psychiatry Chahal, R., Gotlib, I. H., Guyer, A. E. 2020

  View details for DOI 10.1111/jcpp.13250

• Brain structural abnormalities in obesity: relation to age, genetic risk, and common psychiatric disorders : Evidence through univariate and multivariate mega-analysis including 6420 participants from the ENIGMA MDD working group. Molecular psychiatry Opel, N. n., Thalamuthu, A. n., Milaneschi, Y. n., Grotegerd, D. n., Flint, C. n., Leenings, R. n., Goltermann, J. n., Richter, M. n., Hahn, T. n., Woditsch, G. n., Berger, K. n., Hermesdorf, M. n., McIntosh, A. n., Whalley, H. C., Harris, M. A., MacMaster, F. P., Walter, H. n., Veer, I. M., Frodl, T. n., Carballedo, A. n., Krug, A. n., Nenadic, I. n., Kircher, T. n., Aleman, A. n., Groenewold, N. A., Stein, D. J., Soares, J. C., Zunta-Soares, G. B., Mwangi, B. n., Wu, M. J., Walter, M. n., Li, M. n., Harrison, B. J., Davey, C. G., Cullen, K. R., Klimes-Dougan, B. n., Mueller, B. A., Sämann, P. G., Penninx, B. n., Nawijn, L. n., Veltman, D. J., Aftanas, L. n., Brak, I. V., Filimonova, E. A., Osipov, E. A., Reneman, L. n., Schrantee, A. n., Grabe, H. J., Van der Auwera, S. n., Wittfeld, K. n., Hosten, N. n., Völzke, H. n., Sim, K. n., Gotlib, I. H., Sacchet, M. D., Lagopoulos, J. n., Hatton, S. N., Hickie, I. n., Pozzi, E. n., Thompson, P. M., Jahanshad, N. n., Schmaal, L. n., Baune, B. T., Dannlowski, U. n. 2020

  Abstract

  Emerging evidence suggests that obesity impacts brain physiology at multiple levels. Here we aimed to clarify the relationship between obesity and brain structure using structural MRI (n = 6420) and genetic data (n = 3907) from the ENIGMA Major Depressive Disorder (MDD) working group. Obesity (BMI > 30) was significantly associated with cortical and subcortical abnormalities in both mass-univariate and multivariate pattern recognition analyses independent of MDD diagnosis. The most pronounced effects were found for associations between obesity and lower temporo-frontal cortical thickness (maximum Cohen´s d (left fusiform gyrus) = -0.33). The observed regional distribution and effect size of cortical thickness reductions in obesity revealed considerable similarities with corresponding patterns of lower cortical thickness in previously published studies of neuropsychiatric disorders. A higher polygenic risk score for obesity significantly correlated with lower occipital surface area. In addition, a significant age-by-obesity interaction on cortical thickness emerged driven by lower thickness in older participants. Our findings suggest a neurobiological interaction between obesity and brain structure under physiological and pathological brain conditions.

  View details for DOI 10.1038/s41380-020-0774-9

  View details for PubMedID 32467648

• ENIGMA MDD: seven years of global neuroimaging studies of major depression through worldwide data sharing. Translational psychiatry Schmaal, L. n., Pozzi, E. n., C Ho, T. n., van Velzen, L. S., Veer, I. M., Opel, N. n., Van Someren, E. J., Han, L. K., Aftanas, L. n., Aleman, A. n., Baune, B. T., Berger, K. n., Blanken, T. F., Capitão, L. n., Couvy-Duchesne, B. n., R Cullen, K. n., Dannlowski, U. n., Davey, C. n., Erwin-Grabner, T. n., Evans, J. n., Frodl, T. n., Fu, C. H., Godlewska, B. n., Gotlib, I. H., Goya-Maldonado, R. n., Grabe, H. J., Groenewold, N. A., Grotegerd, D. n., Gruber, O. n., Gutman, B. A., Hall, G. B., Harrison, B. J., Hatton, S. N., Hermesdorf, M. n., Hickie, I. B., Hilland, E. n., Irungu, B. n., Jonassen, R. n., Kelly, S. n., Kircher, T. n., Klimes-Dougan, B. n., Krug, A. n., Landrø, N. I., Lagopoulos, J. n., Leerssen, J. n., Li, M. n., Linden, D. E., MacMaster, F. P., M McIntosh, A. n., Mehler, D. M., Nenadić, I. n., Penninx, B. W., Portella, M. J., Reneman, L. n., Rentería, M. E., Sacchet, M. D., G Sämann, P. n., Schrantee, A. n., Sim, K. n., Soares, J. C., Stein, D. J., Tozzi, L. n., van Der Wee, N. J., van Tol, M. J., Vermeiren, R. n., Vives-Gilabert, Y. n., Walter, H. n., Walter, M. n., Whalley, H. C., Wittfeld, K. n., Whittle, S. n., Wright, M. J., Yang, T. T., Zarate, C. n., Thomopoulos, S. I., Jahanshad, N. n., Thompson, P. M., Veltman, D. J. 2020; 10 (1): 172

  Abstract

  A key objective in the field of translational psychiatry over the past few decades has been to identify the brain correlates of major depressive disorder (MDD). Identifying measurable indicators of brain processes associated with MDD could facilitate the detection of individuals at risk, and the development of novel treatments, the monitoring of treatment effects, and predicting who might benefit most from treatments that target specific brain mechanisms. However, despite intensive neuroimaging research towards this effort, underpowered studies and a lack of reproducible findings have hindered progress. Here, we discuss the work of the ENIGMA Major Depressive Disorder (MDD) Consortium, which was established to address issues of poor replication, unreliable results, and overestimation of effect sizes in previous studies. The ENIGMA MDD Consortium currently includes data from 45 MDD study cohorts from 14 countries across six continents. The primary aim of ENIGMA MDD is to identify structural and functional brain alterations associated with MDD that can be reliably detected and replicated across cohorts worldwide. A secondary goal is to investigate how demographic, genetic, clinical, psychological, and environmental factors affect these associations. In this review, we summarize findings of the ENIGMA MDD disease working group to date and discuss future directions. We also highlight the challenges and benefits of large-scale data sharing for mental health research.

  View details for DOI 10.1038/s41398-020-0842-6

  View details for PubMedID 32472038

• Relational Victimization and Telomere Length in Adolescent Girls JOURNAL OF RESEARCH ON ADOLESCENCE Manczak, E. M., Gotlib, I. H. 2020; 30: 39–45

  View details for DOI 10.1111/jora.12447

  View details for Web of Science ID 000508756700003

• Cerebral Blood Flow in 5- To 8-Month-Olds: Regional Tissue Maturity is Associated with Infant Affect. Developmental science Camacho, M. C., King, L. S., Ojha, A., Garcia, C. M., Sisk, L. S., Cichocki, A. C., Humphreys, K. L., Gotlib, I. H. 2019: e12928

  Abstract

  Infancy is marked by rapid neural and emotional development. The relation between brain function and emotion in infancy, however, is not well understood. Methods for measuring brain function predominantly rely on the BOLD signal; however, interpretation of the BOLD signal in infancy is challenging because the neuronal-hemodynamic relation is immature. Regional cerebral blood flow (rCBF) provides a context for the infant BOLD signal and can yield insight into the developmental maturity of brain regions that may support affective behaviors. This study aims to elucidate the relations among rCBF, age, and emotion in infancy. One hundred and seven mothers reported their infants' (infant age M±SD=6.14±0.51months) temperament. A subsample of infants completed MRI scans, thirty-eight of whom produced usable perfusion MRI during natural sleep to quantify rCBF. Mother-infant dyads completed the repeated Still-Face Paradigm, from which infant affect reactivity and recovery to stress were quantified. We tested associations of infant age at scan, temperament factor scores, and observed affect reactivity and recovery with voxel-wise rCBF. Infant age was positively associated with CBF in nearly all voxels, with peaks located in sensory cortices and the ventral prefrontal cortex, supporting the formulation that rCBF is an indicator of tissue maturity. Temperamental negative affect and recovery of positive affect following a stressor were positively associated with rCBF in several cortical and subcortical limbic regions, including the orbitofrontal cortex and inferior frontal gyrus. This finding yields insight into the nature of affective neurodevelopment during infancy. Specifically, infants with relatively increased prefrontal cortex maturity may evidence a disposition toward greater negative affect and negative reactivity in their daily lives yet show better recovery of positive affect following a social stressor.

  View details for DOI 10.1111/desc.12928

  View details for PubMedID 31802580

• Demographic and psychosocial factors associated with hair cortisol concentrations in preschool children. Pediatric research Anand, K. J., Rovnaghi, C. R., Rigdon, J., Qin, F., Tembulkar, S., Murphy, L. E., Barr, D. A., Gotlib, I. H., Tylavsky, F. A. 2019

  Abstract

  BACKGROUND: Early life stress has enduring effects on physical and mental health. Hair cortisol concentrations (HCCs) reflect exposures to contextual stressors in early life, but are understudied in preschool children.METHODS: Hair samples from children (N=693) during clinic visits (CVs) scheduled at 1-4 years (CV1-CV4) were measured using validated assay methods for HCC.RESULTS: HCCs were highest at CV1 and decreased at CV2-CV4, with no sex differences. Black children had higher HCC than White/other children; these differences persisted even after adjusting for socioeconomic factors. Bivariable analyses showed significant effects on HCC for Black race, with specific demographic and psychosocial factors at different ages. Multivariable analyses showed that higher HCC at CV1 were associated with Black race and male sex; at CV2 with Black race, lower maternal self-esteem, socioeconomic adversity, and the child's risk for developmental delay; at CV3 with Black race; at CV4 with maternal depression and the child's prior HCC values.CONCLUSIONS: HCCs were higher in Black children than White/other races; differences were related to maternal factors, socioeconomic adversity, and the child's risk for developmental delay. Public health measures to reduce disparities between Blacks and other races must also consider the long-term effects of chronic stress in early life.

  View details for DOI 10.1038/s41390-019-0691-2

  View details for PubMedID 31791042

• Functional Connectivity Biomarkers of Emotion Regulation That Distinguish Risk for Bipolar Versus Unipolar Depression in Clinically Asymptomatic High-Risk Youth Fischer, A., Nimarko, A., Hagan, K., Gotlib, I., Singh, M. NATURE PUBLISHING GROUP. 2019: 434–35

  View details for Web of Science ID 000509665600788

• Meta-Analysis: Exposure to Early Life Stress and Risk for Depression in Childhood and Adolescence. Journal of the American Academy of Child and Adolescent Psychiatry LeMoult, J., Humphreys, K. L., Tracy, A., Hoffmeister, J., Ip, E., Gotlib, I. H. 2019

  Abstract

  OBJECTIVE: Early life stress (ELS) is associated with increased risk for the development of major depressive disorder (MDD) in adulthood; the degree to which ELS is associated with an early onset of MDD (ie, during childhood or adolescence), however, is not known. In this meta-analysis, we estimated the associations between ELS and the risk for onset of MDD before age 18 years. In addition, we examined the associations between eight specific forms of ELS (ie, sexual abuse, physical abuse, poverty, physical illness/injury, death of a family member, domestic violence, natural disaster, and emotional abuse) and risk for youth-onset MDD.METHOD: We conducted a systematic search in scientific databases for studies that assessed both ELS and the presence or absence of MDD before age 18 years. We identified 62 journal articles with a total of 44,066 unique participants. We assessed study quality using the Newcastle-Ottawa Scale. When heterogeneous effect sizes were detected, we tested whether demographic and/or methodological factors moderated the association between ELS and MDD.RESULTS: Using a random-effects meta-analysis, we found that individuals who experienced ELS were more likely to develop MDD before the age of 18 than were individuals without a history of ELS (OR=2.50; 95% CI [2.08, 3.00]). Separate meta-analyses revealed a range of associations with MDD; while some types of ELS (eg, poverty) were not associated with MDD, other types (eg, emotional abuse) were associated more strongly with MDD than was ELS considered more broadly.CONCLUSION: These findings provide important evidence that the adverse effect of ELS on MDD risk manifests early in development, prior to adulthood, and varies by type of ELS.

  View details for DOI 10.1016/j.jaac.2019.10.011

  View details for PubMedID 31676392

• Depressive Symptoms Predict Change in Telomere Length and Mitochondrial DNA Copy Number Across Adolescence. Journal of the American Academy of Child and Adolescent Psychiatry Humphreys, K. L., Sisk, L. M., Manczak, E. M., Lin, J., Gotlib, I. H. 2019

  Abstract

  OBJECTIVE: Several studies have found associations between a diagnosis or symptoms of major depressive disorder and markers of cellular aging and dysfunction. These investigations, however, are predominantly cross-sectional and focus on adults. In the present study, we used a prospective longitudinal design to test the cross-sectional association between depressive symptoms in adolescents and telomere length (TL) as well as mitochondrial DNA copy number (mtDNA-cn).METHOD: 121 adolescents (Mean age=11.38, SD=1.03; 39 percent male) were followed for approximately two years. At baseline and follow-up, participants provided saliva for DNA extraction, from which measures of TL and mtDNA-cn were obtained. Depressive symptoms were obtained via the Children's Depression Inventory.RESULTS: There was no association between depressive symptoms and markers of cellular aging at baseline; however, depressive symptoms at baseline predicted higher rates of telomere erosion (beta=-.201, p=.016) and greater increases in mtDNA-cn (beta=.190, p=.012) over the follow-up period. Markers of cellular aging at baseline did not predict subsequent changes in depressive symptoms. Furthermore, including number of stressful life events did not alter these patterns of findings.CONCLUSION: These results indicate that depressive symptoms precede changes in cellular aging and dysfunction, rather than the reverse.

  View details for DOI 10.1016/j.jaac.2019.09.031

  View details for PubMedID 31628984

• Early life stress, cortisol, frontolimbic connectivity, and depressive symptoms during puberty DEVELOPMENT AND PSYCHOPATHOLOGY Kircanski, K., Sisk, L. M., Ho, T. C., Humphreys, K. L., King, L. S., Colich, N. L., Ordaz, S. J., Gotlib, I. H. 2019; 31 (3): 1011–22

  View details for DOI 10.1017/S0954579419000555

  View details for Web of Science ID 000474919900017

• Beyond a Binary Classification of Sex: An Examination of Brain Sex Differentiation, Psychopathology, and Genotype JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY Phillips, O. R., Onopa, A. K., Hsu, V., Ollila, H., Hillary, R., Hallmayer, J., Gotlib, I. H., Taylor, J., Mackey, L., Singh, M. K. 2019; 58 (8): 787–98

  View details for DOI 10.1016/j.jaac.2018.09.425

  View details for Web of Science ID 000518530600008

• Time Spent with Parents Predicts Change in Depressive Symptoms in Adolescents with Major Depressive Disorder JOURNAL OF ABNORMAL CHILD PSYCHOLOGY Manczak, E. M., Ordaz, S. J., Singh, M. K., Goyer, M. S., Gotlib, I. H. 2019; 47 (8): 1401–8

  View details for DOI 10.1007/s10802-019-00526-5

  View details for Web of Science ID 000475747900011

• No Alterations of Brain Structural Asymmetry in Major Depressive Disorder: An ENIGMA Consortium Analysis. The American journal of psychiatry de Kovel, C. G., Aftanas, L., Aleman, A., Alexander-Bloch, A. F., Baune, B. T., Brack, I., Bulow, R., Busatto Filho, G., Carballedo, A., Connolly, C. G., Cullen, K. R., Dannlowski, U., Davey, C. G., Dima, D., Dohm, K., Erwin-Grabner, T., Frodl, T., Fu, C. H., Hall, G. B., Glahn, D. C., Godlewska, B., Gotlib, I. H., Goya-Maldonado, R., Grabe, H. J., Groenewold, N. A., Grotegerd, D., Gruber, O., Harris, M. A., Harrison, B. J., Hatton, S. N., Hickie, I. B., Ho, T. C., Jahanshad, N., Kircher, T., Kramer, B., Krug, A., Lagopoulos, J., Leehr, E. J., Li, M., MacMaster, F. P., MacQueen, G., McIntosh, A. M., McLellan, Q., Medland, S. E., Mueller, B. A., Nenadic, I., Osipov, E., Papmeyer, M., Portella, M. J., Reneman, L., Rosa, P. G., Sacchet, M. D., Schnell, K., Schrantee, A., Sim, K., Simulionyte, E., Sindermann, L., Singh, A., Stein, D. J., Ubani, B. N., Van der Wee, N. J., Van der Werff, S. J., Veer, I. M., Vives-Gilabert, Y., Volzke, H., Walter, H., Walter, M., Schreiner, M. W., Whalley, H., Winter, N., Wittfeld, K., Yang, T. T., Yuksel, D., Zaremba, D., Thompson, P. M., Veltman, D. J., Schmaal, L., Francks, C. 2019: appiajp201918101144

  Abstract

  OBJECTIVE: Asymmetry is a subtle but pervasive aspect of the human brain, and it may be altered in several psychiatric conditions. MRI studies have shown subtle differences of brain anatomy between people with major depressive disorder and healthy control subjects, but few studies have specifically examined brain anatomical asymmetry in relation to this disorder, and results from those studies have remained inconclusive. At the functional level, some electroencephalography studies have indicated left fronto-cortical hypoactivity and right parietal hypoactivity in depressive disorders, so aspects of lateralized anatomy may also be affected. The authors used pooled individual-level data from data sets collected around the world to investigate differences in laterality in measures of cortical thickness, cortical surface area, and subcortical volume between individuals with major depression and healthy control subjects.METHODS: The authors investigated differences in the laterality of thickness and surface area measures of 34 cerebral cortical regions in 2,256 individuals with major depression and 3,504 control subjects from 31 separate data sets, and they investigated volume asymmetries of eight subcortical structures in 2,540 individuals with major depression and 4,230 control subjects from 32 data sets. T1-weighted MRI data were processed with a single protocol using FreeSurfer and the Desikan-Killiany atlas. The large sample size provided 80% power to detect effects of the order of Cohen's d=0.1.RESULTS: The largest effect size (Cohen's d) of major depression diagnosis was 0.085 for the thickness asymmetry of the superior temporal cortex, which was not significant after adjustment for multiple testing. Asymmetry measures were not significantly associated with medication use, acute compared with remitted status, first episode compared with recurrent status, or age at onset.CONCLUSIONS: Altered brain macro-anatomical asymmetry may be of little relevance to major depression etiology in most cases.

  View details for DOI 10.1176/appi.ajp.2019.18101144

  View details for PubMedID 31352813

• Irritability and Brain Volume in Adolescents: Cross-sectional and Longitudinal Associations. Social cognitive and affective neuroscience Dennis, E. L., Humphreys, K. L., King, L. S., Thompson, P. M., Gotlib, I. H. 2019

  Abstract

  Irritability is garnering increasing attention in psychiatric research as a transdiagnostic marker of both internalizing and externalizing disorders. These disorders often emerge during adolescence, highlighting the need to examine changes in the brain and in psychological functioning during this developmental period. Adolescents were recruited for a longitudinal study examining the effects of early life stress on the development of psychopathology. 151 adolescents (73 M/78 F, average age=11.5 years, standard deviation=1.1) were scanned with a T1-weighted MRI sequence and parents completed reports of adolescent irritability using the Affective Reactivity Index. Of these 151 adolescents, 94 (46 M/48 F) returned for a second session (average interval=1.9 years, SD=0.4). We used tensor-based morphometry to examine cross-sectional and longitudinal associations between irritability and regional brain volume. Irritability was associated with brain volume across a number of regions. More irritable individuals had larger hippocampi, insula, medial orbitofrontal cortex, and cingulum/cingulate cortex, and smaller putamen and internal capsule. Across the brain, more irritable individuals also had larger volume and less volume contraction in a number of areas that typically decrease in volume over the developmental period studied here, suggesting delayed maturation. These structural changes may increase adolescents' vulnerability for internalizing and externalizing disorders.

  View details for DOI 10.1093/scan/nsz053

  View details for PubMedID 31309969

• Measuring socioeconomic adversity in early life ACTA PAEDIATRICA Anand, K. S., Rigdon, J., Rovnaghi, C. R., Qin, F., Tembulkar, S., Bush, N., LeWinn, K., Tylavsky, F. A., Davis, R., Barr, D. A., Gotlib, I. H. 2019; 108 (7): 1267–77

  View details for DOI 10.1111/apa.14715

  View details for Web of Science ID 000471904300016

• Longitudinal Decreases in Suicidal Ideation are Associated With Increases in Salience Network Coherence in Depressed Adolescents Schwartz, J., Ho, T., Ordaz, S., Gotlib, I. ELSEVIER SCIENCE INC. 2019: S77

  View details for DOI 10.1016/j.biopsych.2019.03.200

  View details for Web of Science ID 000472661000187

• Sensitive Periods of Stress and Adolescent Amygdala-Ventromedial Prefrontal Cortex Connectivity: A Longitudinal Investigation Ho, T., Humphreys, K., King, L., Colich, N., Schwartz, J., Ohashi, K., Teicher, M., Gotlib, I. ELSEVIER SCIENCE INC. 2019: S100

  View details for DOI 10.1016/j.biopsych.2019.03.255

  View details for Web of Science ID 000472661000242

• Higher Concentrations of Interleukin-6 Are Associated With Smaller Nucleus Accumbens Gray Matter Volume and More Severe Symptoms in Depressed Adolescents Ojha, A., Rosenberg-Hasson, Y., Maecker, H., Gotlib, I., Ho, T. ELSEVIER SCIENCE INC. 2019: S164

  View details for DOI 10.1016/j.biopsych.2019.03.416

  View details for Web of Science ID 000472661000398

• Antenatal Depressive Symptoms are Associated With the Trajectory of Hair Cortisol Concentration Across Pregnancy Querdasi, F., King, L., Humphreys, K., Gotlib, I. ELSEVIER SCIENCE INC. 2019: S331

  View details for DOI 10.1016/j.biopsych.2019.03.840

  View details for Web of Science ID 000472661000810

• Higher Levels of Inflammatory Proteins are Associated With Reduced White Matter Integrity in Depressed Adolescents Sisk, L., Kulla, A., Rosenberg-Hasson, Y., Maecker, H., Gotlib, I., Ho, T. ELSEVIER SCIENCE INC. 2019: S251

  View details for DOI 10.1016/j.biopsych.2019.03.636

  View details for Web of Science ID 000472661000612

• Evidence for a sensitive period in the effects of early life stress on hippocampal volume DEVELOPMENTAL SCIENCE Humphreys, K. L., King, L. S., Sacchet, M. D., Camacho, M., Colich, N. L., Ordaz, S. J., Ho, T. C., Gotlib, I. H. 2019; 22 (3)

  View details for DOI 10.1111/desc.12775

  View details for Web of Science ID 000465042300008

• LIFETIME STRESS EXPOSURE, INFLAMMATION, AND DEPRESSION SEVERITY IN DEPRESSED ADOLESCENTS Sanabria, M. M., Ho, T. C., Walker, J. C., Kulla, A., Slavich, G. M., Gotlib, I. H. LIPPINCOTT WILLIAMS & WILKINS. 2019: A22

  View details for Web of Science ID 000467560700064

• A person-centered approach to the assessment of early life stress: Associations with the volume of stress-sensitive brain regions in early adolescence DEVELOPMENT AND PSYCHOPATHOLOGY King, L. S., Humphreys, K. L., Camacho, M., Gotlib, I. H. 2019; 31 (2): 643–55

  View details for DOI 10.1017/S0954579418000184

  View details for Web of Science ID 000466341900019

• Water Contaminant Levels Interact with Parenting Environment to Predict Development of Depressive Symptoms in Adolescents. Developmental science Manczak, E. M., Miller, J. G., Gotlib, I. H. 2019: e12838

  Abstract

  Contaminants in drinking water, such as lead, nitrate, and arsenic, have been linked to negative physical health outcomes. We know less, however, about whether such pollutants also predict mental health problems and, if so, the conditions under which such effects are strongest. In this longitudinal study, we examined whether drinking water contaminants interact with negative family environments (parental psychological control) to predict changes in depressive symptoms in 110 adolescents-a developmental period when symptoms often first emerge. We found that for adolescents in psychologically controlling families, levels of drinking water contaminants prospectively predicted depressive symptoms two years later; this effect was not present in adolescents in non-controlling families. Importantly, these associations were not accounted for by family- or community-level socioeconomic resources, demographic features, or by the adolescents' stress exposure. These findings highlight the interplay of physical and psychological environments in influencing depressive symptoms in adolescents. This article is protected by copyright. All rights reserved.

  View details for PubMedID 31009144

• Resting-state functional connectivity and inflexibility of daily emotions in major depression JOURNAL OF AFFECTIVE DISORDERS Schwartz, J., Ordaz, S. J., Kircanski, K., Ho, T. C., Davis, E. G., Camacho, M., Gotlib, I. H. 2019; 249: 26-34

  View details for DOI 10.1016/j.jad.2019.01.040

  View details for Web of Science ID 000461024900005

• Depression: A cognitive perspective CLINICAL PSYCHOLOGY REVIEW LeMoult, J., Gotlib, I. H. 2019; 69: 51–66

  View details for DOI 10.1016/j.cpr.2018.06.008

  View details for Web of Science ID 000465191700005

• Time Spent with Parents Predicts Change in Depressive Symptoms in Adolescents with Major Depressive Disorder. Journal of abnormal child psychology Manczak, E. M., Ordaz, S. J., Singh, M. K., Goyer, M. S., Gotlib, I. H. 2019

  Abstract

  Research with community samples suggests that non-affective features of families, such as the amount of time parents and adolescents spend together, affect depressive symptoms in adolescents. It is possible, however, that spending time with parents not only protects against the onset of depressive symptoms, but also reduces symptoms in adolescents who are already depressed. The current study was designed to test this formulation while also examining whether affective dimensions of family functioning - specifically parental warmth - accounted for or moderated observed associations. Finally, we tested the reverse direction of the associations, examining whether greater severity of depression in adolescents results in parents spending less time with them. Forty-one adolescents (ages 14 to 17years) who met criteria for a current major depressive episode participated in the present study with one parent. Once each month for six time points, dyads completed reports of depressive symptoms and the amount of time parents and adolescents spent with each other. Participants also completed measures of parental warmth. Results of lagged multilevel modeling indicated that spending more time with a parent predicted fewer depressive symptoms in adolescents at the following assessment relative to their mean; in contrast, greater severity of depressive symptoms did not predict spending less time with a parent at the following assessment. In contrast, parental warmth did not account for or moderate the association between time together and depressive symptoms. These results suggest that non-affective dimensions of family life, specifically spending more time with parents, have beneficial effects on depressive symptoms in adolescents diagnosed with depression.

  View details for PubMedID 30847667

• Reward-circuit biomarkers of risk and resilience in adolescent depression. Journal of affective disorders Fischer, A. S., Ellwood-Lowe, M. E., Colich, N. L., Cichocki, A., Ho, T. C., Gotlib, I. H. 2019; 246: 902-909

  Abstract

  Dysfunctional reward processing is a core feature of major depressive disorder. While there is growing knowledge of reward processing in adolescent depression, researchers have ignored neural mechanisms of resilience to depression. Here, we examine neural correlates of reward processing that characterize resilience and risk in adolescents at risk for depression, facilitating the development of effective intervention approaches that strengthen resilience to psychopathology in at-risk youth.50 adolescent females were followed through age 18: 32 at-risk adolescents who either did (remitted-depressed; n = 15) or did not (resilient; n = 17) experience a depressive episode, and 18 low-risk healthy controls. Participants completed clinical assessments at 18-month intervals and an fMRI reward-processing task in late adolescence. We conducted predictive modeling with a priori reward regions of interest (ROIs).At-risk resilient and remitted-depressed adolescents exhibited less striatal activation than did controls during anticipation of reward. Resilient adolescents exhibited greater activation than did remitted-depressed adolescents in the middle frontal gyrus during reward anticipation, and less activation in the superior frontal gyrus and cuneus during processing of reward outcome. Using predictive modeling, ventral anterior cingulate cortex and putamen activation during reward processing distinguished resilient from remitted-depressed adolescents with 83% accuracy.The relatively small sample size of only females and the fact that fMRI data were obtained at one time point in late adolescence are limitations.Distinct patterns of neural activation in reward circuitry appear to be markers of risk and resilience that may be targets for prevention and treatment approaches aimed at strengthening adaptive reward processing in at-risk adolescents.

  View details for DOI 10.1016/j.jad.2018.12.104

  View details for PubMedID 30795497

  View details for PubMedCentralID PMC6391738

• Stressful Life Events, ADHD Symptoms, and Brain Structure in Early Adolescence JOURNAL OF ABNORMAL CHILD PSYCHOLOGY Humphreys, K. L., Watts, E. L., Dennis, E. L., King, L. S., Thompson, P. M., Gotlib, I. H. 2019; 47 (3): 421-432

  View details for DOI 10.1007/s10802-018-0443-5

  View details for Web of Science ID 000460359800004

• The Neglect-Enrichment Continuum: Characterizing Variation in Early Caregiving Environments. Developmental review : DR King, L. S., Humphreys, K. L., Gotlib, I. H. 2019; 51: 109-122

  View details for DOI 10.1016/j.dr.2019.01.001

  View details for PubMedID 32669751

  View details for PubMedCentralID PMC7363411

• The neglect-enrichment continuum: Characterizing variation in early caregiving environments DEVELOPMENTAL REVIEW King, L. S., Humphreys, K. L., Gotlib, I. H. 2019; 51: 109–22

  View details for DOI 10.1016/j.dr.2019.01.001

  View details for Web of Science ID 000459951300006

• Reward-circuit biomarkers of risk and resilience in adolescent depression JOURNAL OF AFFECTIVE DISORDERS Fischer, A. S., Ellwood-Lowe, M. E., Colich, N. L., Cichocki, A., Ho, T. C., Gotlib, I. H. 2019; 246: 902–9

  View details for DOI 10.1016/j.jad.2018.12.104

  View details for Web of Science ID 000457276200111

• Longitudinal decreases in suicidal ideation are associated with increases in salience network coherence in depressed adolescents JOURNAL OF AFFECTIVE DISORDERS Schwartz, J., Ordaz, S. J., Ho, T. C., Gotlib, I. H. 2019; 245: 545-552

  View details for DOI 10.1016/j.jad.2018.11.009

  View details for Web of Science ID 000456697100068

• Resting-state functional connectivity and inflexibility of daily emotions in major depression. Journal of affective disorders Schwartz, J., Ordaz, S. J., Kircanski, K., Ho, T. C., Davis, E. G., Camacho, M. C., Gotlib, I. H. 2019; 249: 26–34

  Abstract

  BACKGROUND: Major Depressive Disorder (MDD) is characterized by aberrant resting-state functional connectivity (FC) in anterior cingulate regions (e.g., subgenual anterior cingulate [sgACC]) and by negative emotional functioning that is inflexible or resistant to change.METHODS: MDD (N = 33) and control (CTL; N = 31) adults completed a resting-state scan, followed by a smartphone-based Experience Sampling Methodology (ESM) protocol surveying 10 positive and negative emotions 5 times per day for 21 days. We used multilevel modeling to assess moment-to-moment emotional inflexibility (i.e., strong temporal connections between emotions). We examined group differences in whole-brain FC analysis of bilateral sgACC, and then examined associations between emotional experiences and the extracted FC values within each group.RESULTS: As predicted, MDDs had inflexibility in sadness and avoidance (p<.001, FDR-corrected p<.05), indicating that these emotional experiences persist in depression. MDDs showed weaker FC between the right sgACC and pregenual/dorsal anterior cingulate (pg/dACC) than did CTLs (FWE-corrected, voxelwise p=.01). Importantly, sgACC-pg/dACC FC predicted sadness inflexibility in both MDDs (p = .046) and CTLs (p = .033), suggesting that sgACC FC is associated with day-to-day negative emotions.LIMITATIONS: Other maladaptive behaviors likely also affect the flexibility of negative emotions. We cannot generalize our finding of a positive relation between sgACC FC and inflexibility of sadness to individuals with more chronic depression or who have recovered from depression.CONCLUSIONS: Our preliminary findings suggest that connections between portions of the ACC contribute to the persistence of negative emotions and are important in identifying a brain mechanism that may underlie the maintenance of sadness in daily life.

  View details for PubMedID 30743019

• People are Better at Maintaining Positive Than Negative Emotional States EMOTION Waugh, C. E., Running, K. E., Reynolds, O. C., Gotlib, I. H. 2019; 19 (1): 132–45

  Abstract

  Determining how people maintain positive and negative emotional states is critical to understanding emotional dynamics, individual differences in emotion, and the instrumental value of emotions. There has been a surge in interest in tasks assessing affective working memory that can examine how people maintain stimulus-independent positive and negative emotional states. In these tasks, people are asked to maintain their emotional state that was induced by an initial stimulus in order to compare that state with the state induced by a subsequent stimulus. It is unclear, however, whether measures of accuracy in this task actually reflect the success of maintaining the initial emotional state. In a series of studies, we introduce an idiographic metric of accuracy that reflects the success of emotional maintenance and use that metric to examine whether people are better at maintaining positive or negative emotional states. We demonstrate that people are generally better at maintaining positive emotional states than they are at maintaining negative emotional states (Studies 1-3). We also show that this effect is not due to decay or to spontaneous interference processes (Studies 2-3), retroactive interference processes (Studies 4-5), or reduced engagement with the initial emotional state (Study 5). Although the mechanism underlying this effect is not yet clear, our results have important implications for understanding emotional maintenance and the possible functions of positive and negative emotions. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

  View details for PubMedID 29565611

  View details for PubMedCentralID PMC6151172

• Associations Among Early Life Stress, Rumination, Symptoms of Psychopathology, and Sex in Youth in the Early Stages of Puberty: a Moderated Mediation Analysis JOURNAL OF ABNORMAL CHILD PSYCHOLOGY LeMoult, J., Humphreys, K. L., King, L. S., Colich, N. L., Price, A. N., Ordaz, S. J., Gotlib, I. H. 2019; 47 (2): 199–207

  Abstract

  Despite the high prevalence and substantial costs of early life stress (ELS), the mechanisms through which ELS confers risk for psychopathology are poorly understood, particularly among youth who are in an earlier stage of the transition through puberty. We sought to advance our understanding of the link between ELS and psychopathology by testing whether rumination mediates the relation between ELS and symptoms of psychopathology in youth in the early stages of puberty, and whether sex moderates this mediation. We assessed levels of ELS, both brooding and reflection subtypes of rumination, and internalizing and externalizing symptoms in 170 youth in the early stages of puberty (56% girls) ages 9-13 years. Brooding, but not reflection, mediated the relation between ELS and both internalizing and externalizing symptoms. Importantly, however, sex moderated the relation among ELS, brooding, and symptoms. Specifically, brooding mediated the relation between ELS and both internalizing and externalizing symptoms for girls, but not for boys. Findings support the formulation that brooding is a mechanism linking ELS to multiple forms of behavioral and emotional problems exclusively in girls in the early stages of puberty.

  View details for PubMedID 29774495

• Symptoms of social anxiety disorder and major depressive disorder: A network perspective. Journal of affective disorders Langer, J. K., Tonge, N. A., Piccirillo, M., Rodebaugh, T. L., Thompson, R. J., Gotlib, I. H. 2019; 243: 531–38

  Abstract

  BACKGROUND: We used network analyses to examine symptoms that may play a role in the co-occurrence of social anxiety disorder (SAD) and major depressive disorder (MDD). Whereas latent variable models examine relations among latent constructs, network analyses have the advantage of characterizing direct relations among the symptoms themselves.METHOD: We conducted network modeling on symptoms of social anxiety and depression in a clinical sample of 130 women who met criteria for SAD, MDD, both disorders, or had no lifetime history of mental illness.RESULTS: In the resulting network, the core symptoms of social fear and depressed mood appeared at opposite ends of the network and were weakly related; so-called "bridges" between these symptoms appeared to occur via intervening variables. In particular, the worthless variable appeared to play a central role in the network.LIMITATIONS: Because our data were cross-sectional, we are unable to draw conclusions about the direction of these effects or whether these variables are related to each other prospectively.CONCLUSIONS: Continued testing of these pathways using longitudinal data will help facilitate the development of more effective clinical interventions for these disorders.

  View details for PubMedID 30292147

• Symptoms of social anxiety disorder and major depressive disorder: A network perspective JOURNAL OF AFFECTIVE DISORDERS Langer, J. K., Tonge, N. A., Piccirillo, M., Rodebaugh, T. L., Thompson, R. J., Gotlib, I. H. 2019; 243: 531-538

  View details for DOI 10.1016/j.jad.2018.09.078

  View details for Web of Science ID 000446860300068

• Measuring socioeconomic adversity in early life. Acta paediatrica (Oslo, Norway : 1992) Anand, K. J., Rigdon, J., Rovnaghi, C. R., Qin, F., Tembulkar, S., Bush, N., LeWinn, K., Tylavsky, F. A., Davis, R., Barr, D. A., Gotlib, I. H. 2019

  Abstract

  AIM: Early life adversity in leads to enduring effects on physical and mental health, school performance, and other outcomes. We sought to identify potentially modifiable factors leading to socioeconomic adversity in early life.METHODS: We enrolled 1,503 pregnant women aged 16-40 years, without pregnancy complications or pre-existing conditions from Shelby County, Tennessee. Social, familial, and economic variables were analyzed using principal components (PCs) analyses to generate the Socioeconomic Adversity Index (SAI). This was replicated using the National Survey of Children's Health (NSCH). Health and social outcomes were compared across the quintile groups defined by SAI values at the county, state, and national levels.RESULTS: Significant differences occurred across the SAI Quintile-1 to Quintile-5 groups in marital status, household structure, annual income, education, and health insurance. Significantly worse health and social outcomes occurred in the lower vs. higher SAI quintiles, including maternal depression, parental incarceration, child's birthweight, and potential for child abuse. Maternal age and race also differed significantly across the SAI quintiles.CONCLUSION: Modifiable factors contributing to socioeconomic adversity in early life included marital status, household structure, annual income, education, and health insurance. Those exposed to greater socioeconomic adversity as defined by SAI values had significantly worse maternal and child outcomes. This article is protected by copyright. All rights reserved.

  View details for PubMedID 30614554

• Early life stress, cortisol, frontolimbic connectivity, and depressive symptoms during puberty. Development and psychopathology Kircanski, K. n., Sisk, L. M., Ho, T. C., Humphreys, K. L., King, L. S., Colich, N. L., Ordaz, S. J., Gotlib, I. H. 2019: 1–12

  Abstract

  Early life stress (ELS) is a risk factor for the development of depression in adolescence; the mediating neurobiological mechanisms, however, are unknown. In this study, we examined in early pubertal youth the associations among ELS, cortisol stress responsivity, and white matter microstructure of the uncinate fasciculus and the fornix, two key frontolimbic tracts; we also tested whether and how these variables predicted depressive symptoms in later puberty. A total of 208 participants (117 females; M age = 11.37 years; M Tanner stage = 2.03) provided data across two or more assessment modalities: ELS; salivary cortisol levels during a psychosocial stress task; diffusion magnetic resonance imaging; and depressive symptoms. In early puberty there were significant associations between higher ELS and decreased cortisol production, and between decreased cortisol production and increased fractional anisotropy in the uncinate fasciculus. Further, increased fractional anisotropy in the uncinate fasciculus predicted higher depressive symptoms in later puberty, above and beyond earlier symptoms. In post hoc analyses, we found that sex moderated several additional associations. We discuss these findings within a broader conceptual model linking ELS, emotion dysregulation, and depression across the transition through puberty, and contend that brain circuits implicated in the control of hypothalamic-pituitary-adrenal axis function should be a focus of continued research.

  View details for PubMedID 31064568

• Heart rate variability as a biomarker of anxious depression response to antidepressant medication DEPRESSION AND ANXIETY Kircanski, K., Williams, L. M., Gotlib, I. H. 2019; 36 (1): 63–71

  View details for DOI 10.1002/da.22843

  View details for Web of Science ID 000454899400006

• White matter disturbances in major depressive disorder: a coordinated analysis across 20 international cohorts in the ENIGMA MDD working group. Molecular psychiatry van Velzen, L. S., Kelly, S. n., Isaev, D. n., Aleman, A. n., Aftanas, L. I., Bauer, J. n., Baune, B. T., Brak, I. V., Carballedo, A. n., Connolly, C. G., Couvy-Duchesne, B. n., Cullen, K. R., Danilenko, K. V., Dannlowski, U. n., Enneking, V. n., Filimonova, E. n., Förster, K. n., Frodl, T. n., Gotlib, I. H., Groenewold, N. A., Grotegerd, D. n., Harris, M. A., Hatton, S. N., Hawkins, E. L., Hickie, I. B., Ho, T. C., Jansen, A. n., Kircher, T. n., Klimes-Dougan, B. n., Kochunov, P. n., Krug, A. n., Lagopoulos, J. n., Lee, R. n., Lett, T. A., Li, M. n., MacMaster, F. P., Martin, N. G., McIntosh, A. M., McLellan, Q. n., Meinert, S. n., Nenadić, I. n., Osipov, E. n., Penninx, B. W., Portella, M. J., Repple, J. n., Roos, A. n., Sacchet, M. D., Sämann, P. G., Schnell, K. n., Shen, X. n., Sim, K. n., Stein, D. J., van Tol, M. J., Tomyshev, A. S., Tozzi, L. n., Veer, I. M., Vermeiren, R. n., Vives-Gilabert, Y. n., Walter, H. n., Walter, M. n., van der Wee, N. J., van der Werff, S. J., Schreiner, M. W., Whalley, H. C., Wright, M. J., Yang, T. T., Zhu, A. n., Veltman, D. J., Thompson, P. M., Jahanshad, N. n., Schmaal, L. n. 2019

  Abstract

  Alterations in white matter (WM) microstructure have been implicated in the pathophysiology of major depressive disorder (MDD). However, previous findings have been inconsistent, partially due to low statistical power and the heterogeneity of depression. In the largest multi-site study to date, we examined WM anisotropy and diffusivity in 1305 MDD patients and 1602 healthy controls (age range 12-88 years) from 20 samples worldwide, which included both adults and adolescents, within the MDD Working Group of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) consortium. Processing of diffusion tensor imaging (DTI) data and statistical analyses were harmonized across sites and effects were meta-analyzed across studies. We observed subtle, but widespread, lower fractional anisotropy (FA) in adult MDD patients compared with controls in 16 out of 25 WM tracts of interest (Cohen's d between 0.12 and 0.26). The largest differences were observed in the corpus callosum and corona radiata. Widespread higher radial diffusivity (RD) was also observed (all Cohen's d between 0.12 and 0.18). Findings appeared to be driven by patients with recurrent MDD and an adult age of onset of depression. White matter microstructural differences in a smaller sample of adolescent MDD patients and controls did not survive correction for multiple testing. In this coordinated and harmonized multisite DTI study, we showed subtle, but widespread differences in WM microstructure in adult MDD, which may suggest structural disconnectivity in MDD.

  View details for DOI 10.1038/s41380-019-0477-2

  View details for PubMedID 31471575

• Fine Particle Air Pollution and Physiological Reactivity to Social Stress in Adolescence: The Moderating Role of Anxiety and Depression. Psychosomatic medicine Miller, J. G., Gillette, J. S., Manczak, E. M., Kircanski, K. n., Gotlib, I. H. 2019; 81 (7): 641–48

  Abstract

  Exposure to high levels of fine particle air pollution (PM2.5) is associated with adolescent pathophysiology. It is unclear, however, if PM2.5 is associated with physiology within psychosocial contexts, such as social stress, and whether some adolescents are particularly vulnerable to PM2.5-related adverse effects. This study examined the association between PM2.5 and autonomic reactivity to social stress in adolescents and tested whether symptoms of anxiety and depression moderated this association.Adolescents from Northern California (N = 144) participated in a modified Trier Social Stress Test while providing high-frequency heart rate variability and skin conductance level data. PM2.5 data were recorded from CalEnviroScreen. Adolescents reported on their own symptoms of anxiety and depression using the Youth Self-Report, which has been used in prior studies and has good psychometric properties (Cronbach's α in this sample was .86).Adolescents residing in neighborhoods characterized by higher concentrations of PM2.5 demonstrated greater autonomic reactivity (i.e., indexed by lower heart rate variability and higher skin conductance level) (β = .27; b = .44, p = .001, 95% CI = 0.19 to 0.68) in response to social stress; this association was not accounted for by socioeconomic factors. In addition, adolescents who reported more severe anxiety and depression symptoms showed the strongest association between PM2.5 and autonomic reactivity to social stress (β = .53; b = .86, p < .001, 95% CI = 0.48 to 1.23).Exposure to PM2.5 may heighten adolescent physiological reactivity to social stressors. Moreover, adolescents who experience anxiety and depression may be particularly vulnerable to the adverse effects of PM2.5 on stress reactivity.

  View details for DOI 10.1097/PSY.0000000000000714

  View details for PubMedID 31460967

• Neural responses to monetary incentives in bipolar disorder. NeuroImage. Clinical Johnson, S. L., Mehta, H. n., Ketter, T. A., Gotlib, I. H., Knutson, B. n. 2019; 24: 102018

  Abstract

  Although behavioral sensitivity to reward predicts the onset and course of mania in bipolar disorder, the evidence for neural abnormalities in reward processing in bipolar disorder is mixed. To probe neural responsiveness to anticipated and received rewards in the context of bipolar disorder, we scanned individuals with remitted bipolar I disorder (n = 24) and well-matched controls (n = 24; matched for age and gender) using Functional Magnetic Resonance Imaging (FMRI) during a Monetary Incentive Delay (MID) task. Relative to controls, the bipolar group showed reduced NAcc activity during anticipation of gains. Across groups, this blunting correlated with individual differences in impulsive responses to positive emotions (Positive Urgency), which statistically accounted for the association of blunted NAcc activity with bipolar diagnosis. These results suggest that blunted NAcc responses during gain anticipation in the context of bipolar disorder may reflect individual differences in Positive Urgency. These findings may help resolve discrepancies in the literature on neural responses to reward in bipolar disorder, and clarify the relationship between brain activity and the propensity to experience manic episodes.

  View details for DOI 10.1016/j.nicl.2019.102018

  View details for PubMedID 31670069

• Lipid Profiles at Birth Predict Teacher-Rated Child Emotional and Social Development 5 Years Later. Psychological science Manczak, E. M., Gotlib, I. H. 2019: 956797619885649

  Abstract

  The fetal environment has been increasingly implicated in later psychological health, but the role of lipids is unknown. Drawing on the ethnically diverse Born in Bradford (BiB) birth cohort, the current study related levels of high-density lipoprotein (HDL), very-low-density lipoprotein (VLDL), and triglycerides in umbilical cord blood to 1,369 children's teacher-rated psychosocial competence approximately 5 years later. Results of ordinal logistic regressions indicated that low levels of HDL, high levels of VLDL, and high levels of triglycerides predicted greater likelihood of being rated as less competent in domains of emotion regulation, self-awareness, and interpersonal functioning. Furthermore, these results generalized across ethnic background and children's sex and were not accounted for by variables reflecting mothers' psychological or physical health, children's physical health, or children's special education status. Together, these results identify fetal exposure to anomalous lipid levels as a possible contributor to subsequent psychological health and social functioning.

  View details for DOI 10.1177/0956797619885649

  View details for PubMedID 31710576

• Irritability, Externalizing, and Internalizing Psychopathology in Adolescence: Cross-Sectional and Longitudinal Associations and Moderation by Sex JOURNAL OF CLINICAL CHILD AND ADOLESCENT PSYCHOLOGY Humphreys, K. L., Schouboe, S. F., Kircanski, K., Leibenluft, E., Stringaris, A., Gotlib, I. H. 2019; 48 (5): 781–89

  View details for DOI 10.1080/15374416.2018.1460847

  View details for Web of Science ID 000483281600008

• ASSOCIATIONS BETWEEN MATERNAL DEPRESSION AND INFANT FRONTO-LIMBIC CONNECTIVITY Dennis, E. L., Singh, A., Corbin, C. K., Jahanshad, N., Ho, T. C., King, L. S., Borchers, L. R., Humphreys, K. L., Thompson, P. M., Gotlib, I. H., IEEE IEEE. 2019: 126–30

  View details for Web of Science ID 000485040000030

• DNA methylation of HPA-axis genes and the onset of major depressive disorder in adolescent girls: a prospective analysis. Translational psychiatry Humphreys, K. L., Moore, S. R., Davis, E. G., MacIsaac, J. L., Lin, D. T., Kobor, M. S., Gotlib, I. H. 2019; 9 (1): 245

  Abstract

  The stress response system is disrupted in individuals with major depressive disorder (MDD) as well as in those at elevated risk for developing MDD. We examined whether DNA methylation (DNAm) levels of CpG sites within HPA-axis genes predict the onset of MDD. Seventy-seven girls, approximately half (n = 37) of whom were at familial risk for MDD, were followed longitudinally. Saliva samples were taken in adolescence (M age = 13.06 years [SD = 1.52]) when participants had no current or past MDD diagnosis. Diagnostic interviews were administered approximately every 18 months until the first onset of MDD or early adulthood (M age of last follow-up = 19.23 years [SD = 2.69]). We quantified DNAm in saliva samples using the Illumina EPIC chip and examined CpG sites within six key HPA-axis genes (NR3C1, NR3C2, CRH, CRHR1, CRHR2, FKBP5) alongside 59 genotypes for tagging SNPs capturing cis genetic variability. DNAm levels within CpG sites in NR3C1, CRH, CRHR1, and CRHR2 were associated with risk for MDD across adolescence and young adulthood. To rule out the possibility that findings were merely due to the contribution of genetic variability, we re-analyzed the data controlling for cis genetic variation within these candidate genes. Importantly, methylation levels in these CpG sites continued to significantly predict the onset of MDD, suggesting that variation in the epigenome, independent of proximal genetic variants, prospectively predicts the onset of MDD. These findings suggest that variation in the HPA axis at the level of the methylome may predict the development of MDD.

  View details for DOI 10.1038/s41398-019-0582-7

  View details for PubMedID 31582756

• Reply to: Sample Size, Model Robustness, and Classification Accuracy in Diagnostic Multivariate Neuroimaging Analyses BIOLOGICAL PSYCHIATRY Kambeitz, J., Cabral, C., Sacchet, M. D., Gotlib, I. H., Zahn, R., Serpa, M. H., Walter, M., Falkai, P., Koutsouleris, N. 2018; 84 (11): E81–E82

  View details for PubMedID 29580572

• Subcortical Shape Alterations in Major Depressive Disorder: Meta-Analytic Findings From the ENIGMA MDD Working Group Ho, T., Gutman, B., Pozzi, E., Grabe, H., Wittfeld, K., Dannlowski, U., Baune, B., Krug, A., Kircher, T., Veltman, D., Walter, H., Veer, I., Gotlib, I., Sacchet, M., Groenewold, N., Aleman, A., Walter, M., Li, M., Jahanshad, N., Thompson, P., Samann, P., Schmaal, L. NATURE PUBLISHING GROUP. 2018: S285-S286

  View details for Web of Science ID 000509546600529

• Reward-Circuit Biomarkers of Risk and Resilience in Adolescent Depression Fischer, A., Ellwood-Lowe, M., Colich, N., Cichocki, A., Ho, T., Gotlib, I. NATURE PUBLISHING GROUP. 2018: S126

  View details for Web of Science ID 000509546600246

• Striatal dopamine deficits predict reductions in striatal functional connectivity in major depression: a concurrent 11C-raclopride positron emission tomography and functional magnetic resonance imaging investigation. Translational psychiatry Hamilton, J. P., Sacchet, M. D., Hjornevik, T., Chin, F. T., Shen, B., Kampe, R., Park, J. H., Knutson, B. D., Williams, L. M., Borg, N., Zaharchuk, G., Camacho, M. C., Mackey, S., Heilig, M., Drevets, W. C., Glover, G. H., Gambhir, S. S., Gotlib, I. H. 2018; 8 (1): 264

  Abstract

  Major depressive disorder (MDD) is characterized by the altered integration of reward histories and reduced responding of the striatum. We have posited that this reduced striatal activation in MDD is due to tonically decreased stimulation of striatal dopamine synapses which results in decremented propagation of information along the cortico-striatal-pallido-thalamic (CSPT) spiral. In the present investigation, we tested predictions of this formulation by conducting concurrent functional magnetic resonance imaging (fMRI) and 11C-raclopride positron emission tomography (PET) in depressed and control (CTL) participants. We scanned 16 depressed and 14 CTL participants with simultaneous fMRI and 11C-raclopride PET. We estimated raclopride binding potential (BPND), voxel-wise, and compared MDD and CTL samples with respect to BPND in the striatum. Using striatal regions that showed significant between-group BPND differences as seeds, we conducted whole-brain functional connectivity analysis using the fMRI data and identified brain regions in each group in which connectivity with striatal seed regions scaled linearly with BPND from these regions. We observed increased BPND in the ventral striatum, bilaterally, and in the right dorsal striatum in the depressed participants. Further, we found that as BPND increased in both the left ventral striatum and right dorsal striatum in MDD, connectivity with the cortical targets of these regions (default-mode network and salience network, respectively) decreased. Deficits in stimulation of striatal dopamine receptors in MDD could account in part for the failure of transfer of information up the CSPT circuit in the pathophysiology of this disorder.

  View details for PubMedID 30504860

• Striatal dopamine deficits predict reductions in striatal functional connectivity in major depression: a concurrent C-11-raclopride positron emission tomography and functional magnetic resonance imaging investigation TRANSLATIONAL PSYCHIATRY Hamilton, J., Sacchet, M. D., Hjornevik, T., Chin, F. T., Shen, B., Kampe, R., Park, J., Knutson, B. D., Williams, L. M., Borg, N., Zaharchuk, G., Camacho, M., Mackey, S., Heilig, M., Drevets, W. C., Glover, G. H., Gambhir, S. S., Gotlib, I. H. 2018; 8

  View details for DOI 10.1038/s41398-018-0316-2

  View details for Web of Science ID 000452318900002

• Evidence for a Sensitive Period in the Effects of Early Life Stress on Hippocampal Volume. Developmental science Humphreys, K. L., King, L. S., Sacchet, M. D., Camacho, C., Colich, N. L., Ordaz, S. J., Ho, T. C., Gotlib, I. H. 2018: e12775

  Abstract

  Exposure to stress has been causally linked to changes in hippocampal volume (HV). Given that the hippocampus undergoes rapid changes in the first years of life, stressful experiences during this period may be particularly important in understanding individual differences in the development of the hippocampus. One hundred seventy-eight early adolescents (ages 9-13 years; 43% male) were interviewed regarding exposure to and age of onset of experiences of stress; the severity of each stressful event was rated by an objective panel. All participants underwent structural magnetic resonance imaging, from which HVs were automatically segmented. Without considering the age of onset for stressful experiences, there was a small but statistically significant negative association of stress severity with bilateral HV. When considering the age of onset, there was a moderate and significant negative association between stress severity during early childhood (through age 5 years) and HV; there was no association between stress severity during later childhood and HV (age 6 years and older). We provide evidence of a sensitive period through age 5 years for the effects of life stress on HV in adolescence. It will be important in future research to elucidate how reduced HV stemming from early life stress may contribute to stress-related health outcomes. This article is protected by copyright. All rights reserved.

  View details for PubMedID 30471167

• Longitudinal decreases in suicidal ideation are associated with increases in salience network coherence in depressed adolescents. Journal of affective disorders Schwartz, J., Ordaz, S. J., Ho, T. C., Gotlib, I. H. 2018; 245: 545–52

  Abstract

  BACKGROUND: Suicidal ideation (SI) is an important predictor of suicide attempt, yet SI is difficult to predict. Given that SI begins in adolescence when brain networks are maturing, it is important to understand associations between network functioning and changes in severity of SI.METHODS: Thirty-three depressed adolescents were administered the Columbia-Suicide Severity Rating Scale to assess SI and completed resting-state fMRI at baseline (T1) and 6 months later (T2). We computed coherence in the executive control (ECN), default mode (DMN), salience (SN), and non-relevant noise networks and then examined the association between changes in brain network coherence and changes in SI severity from T1 to T2.RESULTS: A greater reduction in severity of SI was associated with a stronger increase in SN coherence from T1 to T2. There were no associations between the other networks and SI.LIMITATIONS: We cannot generalize our findings to more psychiatrically diverse samples. More time-points are necessary to understand the trajectory of SI and SN coherence change.CONCLUSIONS: Our finding that reductions in SI are associated with increases in SN coherence extends previous cross-sectional results documenting a negative association between SI severity and SN coherence. The SN is involved in coordinating activation of ECN and DMN in response to salient information. Given this regulatory role of the SN, the association between SN coherence and SI suggests that adolescents with reduced SN coherence might more easily engage in harmful thoughts. Thus, the SN may be particularly relevant as a target for treatment applications in depressed adolescents.

  View details for PubMedID 30439679

• Reduced dorsal striatal gray matter volume predicts implicit suicidal ideation in adolescents SOCIAL COGNITIVE AND AFFECTIVE NEUROSCIENCE Ho, T. C., Cichocki, A. C., Gifuni, A. J., Camacho, M., Ordaz, S. J., Singh, M. K., Gotlib, I. H. 2018; 13 (11): 1215-1224

  View details for DOI 10.1093/scan/nsy089

  View details for Web of Science ID 000456665500010

• Heart rate variability as a biomarker of anxious depression response to antidepressant medication. Depression and anxiety Kircanski, K., Williams, L. M., Gotlib, I. H. 2018

  Abstract

  BACKGROUND: There is a need to identify biomarkers of treatment outcomes for major depressive disorder (MDD) that can be disseminated. We investigated the predictive utility of pretreatment heart rate variability (HRV) for outcomes of antidepressant medication in MDD, with pretreatment anxious depression as a hypothesized moderator of HRV effects.METHODS: A large, randomized, multicenter practical trial (International Study to Predict Optimized Treatment in Depression) in patients with current nonpsychotic MDD (N=1,008; 722 completers) had three arms: escitalopram, sertraline, and venlafaxine-extended release. At pretreatment, patients were defined as having anxious (N=309) versus nonanxious (N=413) depression and their resting high-frequency HRV (root mean square of successive differences) was assessed. Patients' usual treating clinicians managed medication. At 8weeks, primary outcomes were clinician-rated depressive symptom response and remission; secondary outcomes were self-reported response and remission.RESULTS: Pretreatment HRV predicted antidepressant outcomes as a function of anxious versus nonanxious depression. In anxious depression, patients with higher HRV had better outcomes, whereas patients with lower HRV had poorer outcomes. In nonanxious depression, patients with lower HRV had better outcomes, whereas patients with higher HRV had poorer outcomes. Some simple effects were not significant. Results did not differ by treatment arm and remained significant when controlling for important covariates.CONCLUSIONS: These findings inform a precision medicine approach in which clinical and biological assessments may be integrated to facilitate treatment outcome prediction. Knowing about HRV may help determine which patients with anxious depression could benefit from antidepressants and which patients may require a different treatment approach.

  View details for PubMedID 30311742

• Beyond a Binary Classification of Sex: An Examination of Brain Sex Differentiation, Psychopathology, and Genotype. Journal of the American Academy of Child and Adolescent Psychiatry Phillips, O. R., Onopa, A. K., Hsu, V., Ollila, H. M., Hillary, R. P., Hallmayer, J., Gotlib, I. H., Taylor, J., Mackey, L., Singh, M. K. 2018

  Abstract

  OBJECTIVE: Sex differences in the brain are traditionally treated as binary. We present new evidence that a continuous measure of sex differentiation of the brain can explain sex differences in psychopathology. The degree of sex differentiated brain features (ie, features that are more common in one sex) may predispose individuals toward sex-biased psychopathology and may also be influenced by the genome. We hypothesized that individuals with a female-biased differentiation score would have greater female-biased psychopathology (internalizing symptoms, such as anxiety and depression), whereas individuals with a male-biased differentiation score would have greater male-biased psychopathology (externalizing symptoms, such as disruptive behaviors).METHOD: Using the Philadelphia Neurodevelopmental Cohort database acquired from database of Genotypes and Phenotypes, we calculated the sex differentiation measure, a continuous data-driven calculation of each individual's degree of sex differentiating features extracted from multimodal brain imaging data (Magnetic resonance imaging (MRI) /Diffusion MRI) from the imaged participants (n=866, 407F/459M).RESULTS: In males, higher differentiation scores were correlated with higher levels of externalizing symptoms (r=0.119, p=0.016). The differentiation measure reached genome-wide association study significance (p<5*10-8) in males with single nucleotide polymorphisms Chromsome5:rs111161632:RASGEF1C and Chromosome19:rs75918199:GEMIN7, and in females with Chromosome2:rs78372132:PARD3B and Chromosome15:rs73442006:HCN4.CONCLUSION: The sex differentiation measure provides an initial topography of quantifying male and female brain features. This demonstration that the sex of the human brain can be conceptualized on a continuum has implications for both the presentation of psychopathology and the relation of the brain with genetic variants that may be associated with brain differentiation.

  View details for PubMedID 30768381

• Limbic Intrinsic Connectivity in Depressed and High-Risk Youth. Journal of the American Academy of Child and Adolescent Psychiatry Singh, M. K., Leslie, S. M., Packer, M. M., Weisman, E. F., Gotlib, I. H. 2018; 57 (10): 775

  Abstract

  OBJECTIVE: Depression runs in families and has been associated with dysfunctional limbic connectivity. Whether aberrant limbic connectivity is a risk factor for or a consequence of depression is unclear. To examine this question, we compared resting state functional connectivity (RSFC) in youth with depressive disorders (DEP), healthy offspring of parents with depression (DEP-risk), and healthy comparison (HC) youth.METHOD: Magnetic resonance imaging at rest was acquired from 119 youth, aged 8 to 17 years (DEP, n= 41, DEP-risk, n= 39, and HC, n= 39) and analyzed using seed-based RSFC in bilateral amygdala and nucleus accumbens (NAcc), covarying for age, IQ, and sex.RESULTS: We found distinct risk- and disorder-specific patterns of RSFC across groups. DEP-risk and DEP youth shared reduced negative amygdala-right frontal cortex RSFC and reduced positive amygdala-lingual gyrus RSFC compared to HC youth (p< .001). DEP-risk youth had weaker negative amygdala-precuneus RSFC compared to DEP and HC youth (p< .001), suggesting a resilience marker for depression. In contrast, DEP youth had increased positive NAcc-left frontal cortex RSFC and reduced positive NAcc-insula RSFC compared to DEP-risk and HC youth (p<.001), suggestive of disorder-specific features of depression. Greater depression severity was correlated with disorder-specific amygdala and NAcc RSFC (p< .05).CONCLUSION: RSFC in the amygdala and NAcc may represent selective disorder- and risk-specific markers in youth with, and at familial risk for, depression. Longitudinal studies are needed to determine whether these patterns predict long-term clinical outcomes.

  View details for PubMedID 30274652

• Limbic Intrinsic Connectivity in Depressed and High-Risk Youth JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY Singh, M. K., Leslie, S. M., Packer, M. M., Weisman, E. F., Gotlib, I. H. 2018; 57 (10): 775-+

  View details for DOI 10.1016/j.jaac.2018.06.017

  View details for Web of Science ID 000453802800011

• Maternal depressive symptoms, self-focus, and caregiving behavior JOURNAL OF AFFECTIVE DISORDERS Humphreys, K. L., King, L. S., Choi, P., Gotlib, I. H. 2018; 238: 465-471

  View details for DOI 10.1016/j.jad.2018.05.072

  View details for Web of Science ID 000439557000063

• Reduced dorsal striatal gray matter volume predicts implicit suicidal ideation in adolescents. Social cognitive and affective neuroscience Ho, T. C., Cichocki, A., Gifuni, A. J., Catalina Camacho, M., Ordaz, S. J., Singh, M. K., Gotlib, I. H. 2018

  Abstract

  Suicidal ideation (SI), a potent risk factor for suicide attempts, increases in adolescence. While alterations in dopaminergic functioning have been implicated in suicidal acts-particularly in adults-we do not know whether morphological alterations in dopamine-rich regions of the brain, such as the striatum, are vulnerability factors for the emergence of SI in adolescents. At baseline, a community sample of 152 adolescents (89 female; mean age: 11.41 ± 1.01 years) completed an MRI scan that was used to estimate gray matter volumes (GMV) of three striatal structures: caudate, nucleus accumbens, and putamen. At a 24-month follow-up session, participants completed a self-report measure of suicidal ideation frequency (SIQ) and the death-version of the Implicit Association Test (IAT). Robust linear regression models were conducted to predict SIQ and IAT scores from striatal GMV. Bilateral putamen and left caudate GMV significantly predicted IAT scores (all ps<0.03). No other associations were significant (all ps>0.05). Our finding of reduced dorsal striatal GMV predicting implicit SI may indicate that downstream dopaminergic dysfunction is implicated in the development of overt suicidal behaviors. Self-reported SI was not associated with striatal GMV, suggesting that biological correlates of suicide risk may correlate specifically with objective measurements of SI in adolescents.

  View details for PubMedID 30256980

• Relational Victimization and Telomere Length in Adolescent Girls. Journal of research on adolescence : the official journal of the Society for Research on Adolescence Manczak, E. M., Gotlib, I. H. 2018

  Abstract

  An emerging body of research suggests that telomere length (TL)-a measure of cellular aging-is inversely associated with experiences of childhood stress. Given the salience of peer relationships in childhood and adolescence, we tested whether relational victimization is a unique and specific predictor of salivary TL in girls. Results examining 122 girls (ages 9-15) revealed that greater relational victimization was related to shorter TL but that similar associations were not evident for other measures of social relationships nor accounted for by factors related to depression, life stress, or 5-HTTLPR genotype. The present findings suggest that relational victimization is uniquely associated with TL in adolescence, revealing a link between key aspects of social relationships and biological processes.

  View details for PubMedID 30133038

• Neural correlates of top-down regulation and generation of negative affect in major depressive disorder PSYCHIATRY RESEARCH-NEUROIMAGING Davis, E., Foland-Ross, L. C., Gotlib, I. H. 2018; 276: 1–8

  Abstract

  Major depressive disorder (MDD) is characterized by biased information processing that leads to difficulties regulating negative affect, which includes difficulty decreasing negative affect as well as maladaptively increasing negative affect via cognitive processes. To examine the underlying neural correlates, we scanned depressed and never-depressed adults as they completed a cognitive reappraisal task which required decreasing negative affect while viewing a negative image (down-regulation) and increasing negative affect while viewing a neutral image (emotion generation). Compared to control participants, MDD participants had less recruitment of the dorsal anterior cingulate (dACC) and supplementary motor area (SMA) during early phases of down-regulation, the latter associated with poorer negative affect regulation. Further, MDD participants exhibited greater recruitment of the right middle temporal gyrus (MTG) during emotion generation, which was associated with lower negative affect. Dysregulated negative affect in MDD may be due to impairments in efficiently activating the dACC and SMA to meet regulation demands, and maladaptive generation of negative affect that characterizes individuals with MDD may be counteracted by compensatory activation in the MTG. Elucidating neural mechanisms that underlie the generation of negative affect in the absence of external stimuli is an important extension of previous work examining dysfunctional emotional processes in MDD.

  View details for PubMedID 29689500

• Depression: A cognitive perspective. Clinical psychology review LeMoult, J., Gotlib, I. H. 2018

  Abstract

  Cognitive science has been instrumental in advancing our understanding of the onset, maintenance, and treatment of depression. Research conducted over the last 50 years supports the proposition that depression and risk for depression are characterized by the operation of negative biases, and often by a lack of positive biases, in self-referential processing, interpretation, attention, and memory, as well as the use of maladaptive cognitive emotion regulation strategies. There is also evidence to suggest that deficits in cognitive control over mood-congruent material underlie these cognitive processes. Specifically, research indicates that difficulty inhibiting and disengaging from negative material in working memory: (1) increases the use of maladaptive emotion regulation strategies (e.g., rumination), decreases the use of adaptive emotion regulation strategies (e.g., reappraisal), and potentially impedes flexible selection and implementation of emotion regulation strategies; (2) is associated with negative biases in attention; and (3) contributes to negative biases in long-term memory. Moreover, studies suggest that these cognitive processes exacerbate and sustain the negative mood that typifies depressive episodes. In this review, we present evidence in support of this conceptualization of depression and discuss implications of research findings for theory and practice. Finally, we advance directions for future research.

  View details for PubMedID 29961601

• Maternal depressive symptoms, self-focus, and caregiving behavior. Journal of affective disorders Humphreys, K. L., King, L. S., Choi, P., Gotlib, I. H. 2018; 238: 465–71

  Abstract

  BACKGROUND: Parent-child interactions set the stage for child mental health and development. Given that maternal depressive symptoms are associated with poorer observed caregiving behaviors, examining potential cognitive mediators is important for identifying mechanisms underlying the intergenerational transmission of risk and possible targets for intervention.METHODS: We assessed depressive symptoms and levels of self-focus and psychological distancing from infant-centered verbal narratives obtained from 54 mothers, and examined caregiving behaviors in a structured interaction with their six-month-old infants.RESULTS: Higher depressive symptoms were associated with pronoun use in narratives (i.e., greater "I" and reduced "we" use), reflecting increased self-focus and psychological distancing. Further, increased self-focus was associated with lower levels of caregiver warmth, and mediated the association between depressive symptoms and caregiving warmth.LIMITATIONS: This observational study does not allow for causal interpretations.CONCLUSION: These findings suggest that the cognitive styles associated with depression interfere with the caregiving relationship, affecting behavior in parent-child interactions that may increase the risk for the intergenerational transmission of depression.

  View details for PubMedID 29929156

• Self-reported neglect, amygdala volume, and symptoms of anxiety 1 in adolescent boys CHILD ABUSE & NEGLECT Roth, M. C., Humphreys, K. L., King, L. S., Gotlib, I. H. 2018; 80: 80–89

  Abstract

  Experiences of psychosocial neglect affect the developing brain and may place individuals at increased risk for anxiety. The majority of research in this area has focused on children who have experienced severe psychosocial deprivation; it is not clear whether typical variation in neglect experienced in community samples would have the same neurobiological consequences as those documented in extreme samples. The present study examined the associations among self-reported childhood neglect, amygdala volume, and anxiety symptoms in a community sample of 138 adolescents ages 9-15 years (43% male). Linear mixed modeling yielded a three-way interaction of neglect, sex, and brain hemisphere, reflecting a significant positive association between neglect and right amygdala volume in boys. Additional analyses indicated that right amygdala volume significantly mediated the association between neglect and anxiety symptoms in boys. These findings are consistent with previous reports of larger amygdala volumes in previously institutionalized children, and with documented associations between caregiving deprivation and anxiety symptoms. The results suggest that the effects of childhood neglect on limbic structures are sex-specific and lateralized, and provide support for a neural mechanism relating childhood neglect to later difficulties in emotional functioning.

  View details for PubMedID 29574295

• Stressful Life Events, ADHD Symptoms, and Brain Structure in Early Adolescence. Journal of abnormal child psychology Humphreys, K. L., Watts, E. L., Dennis, E. L., King, L. S., Thompson, P. M., Gotlib, I. H. 2018

  Abstract

  Despite a growing understanding that early adversity in childhood broadly affects risk for psychopathology, the contribution of stressful life events to the development of symptoms of attention-deficit/hyperactivity disorder (ADHD) is not clear. In the present study, we examined the association between number of stressful life events experienced and ADHD symptoms, assessed using the Attention Problems subscale of the Child Behavior Checklist, in a sample of 214 children (43% male) ages 9.11-13.98years (M=11.38, SD=1.05). In addition, we examined whether the timing of the events (i.e., onset through age 5years or after age 6years) was associated with ADHD symptoms. Finally, we examined variation in brain structure to determine whether stressful life events were associated with volume in brain regions that were found to vary as a function of symptoms of ADHD. We found a small to moderate association between number of stressful life events and ADHD symptoms. Although the strength of the associations between number of events and ADHD symptoms did not differ as a function of the age of occurrence of stressful experiences, different brain regions were implicated in the association between stressors and ADHD symptoms in the two age periods during which stressful life events occurred. These findings support the hypothesis that early adversity is associated with ADHD symptoms, and provide insight into possible brain-based mediators of this association.

  View details for PubMedID 29785533

• A person-centered approach to the assessment of early life stress: Associations with the volume of stress-sensitive brain regions in early adolescence. Development and psychopathology King, L. S., Humphreys, K. L., Camacho, M. C., Gotlib, I. H. 2018: 1–13

  Abstract

  Researchers are becoming increasingly interested in linking specific forms of early life stress (ELS) to specific neurobiological markers, including alterations in the morphology of stress-sensitive brain regions. We used a person-centered, multi-informant approach to investigate the associations of specific constellations of ELS with hippocampal and amygdala volume in a community sample of 211 9- to 13-year-old early adolescents. Further, we compared this approach to a cumulative risk model of ELS, in which ELS was quantified by the total number of stressors reported. Using latent class analysis, we identified three classes of ELS (labeled typical/low, family instability, and direct victimization) that were distinguished by experiences of family instability and victimization. Adolescents in the direct victimization class had significantly smaller hippocampal volume than did adolescents in the typical/low class; ELS classes were not significantly associated with amygdala volume. The cumulative risk model of ELS had a poorer fit than did the person-centered model; moreover, cumulative ELS was not significantly associated with hippocampal or amygdala volume. Our results underscore the utility of taking a person-centered approach to identify alterations in stress-sensitive brain regions based on constellations of ELS, and suggest victimization is specifically associated with hippocampal hypotrophy observed in early adolescence.

  View details for PubMedID 29716668

• Differing Windows of Sensitivity to Stress in Amygdala-Ventromedial Prefrontal Cortex Structural and Functional Connectivity: Implications for the Neurobiology of Depression in Youth Ho, T., Humphreys, K., King, L., Colich, N., Schwartz, J., Leong, J., Ohashi, K., Teicher, M., Gotlib, I. ELSEVIER SCIENCE INC. 2018: S81

  View details for Web of Science ID 000432466300201

• Neural Markers of Resilience in Adolescent Females at Familial Risk for Major Depressive Disorder JAMA PSYCHIATRY Fischer, A. S., Camacho, C., Ho, T. C., Whitfield-Gabrieli, S., Gotlib, I. H. 2018; 75 (5): 493–502

  Abstract

  Adolescence is a neurodevelopmental period during which experience-dependent plasticity in brain circuitry may confer vulnerability to depression as well as resilience to disorder. Little is known, however, about the neural mechanisms that underlie resilience during this critical period of brain development.To examine neural functional connectivity correlates of resilience in adolescent females at high and low familial risk for depression who did and did not develop the disorder.A longitudinal study was conducted at Stanford University from October 1, 2003, to January 31, 2017. Sixty-five female adolescents participated in the study: 20 at high risk in whom depression did not develop (resilient), 20 at high risk in whom depression developed (converted), and 25 at low risk with no history of psychopathology (control).We compared functional connectivity between resilient and converted, and between resilient and control, adolescent females using voxelwise 2-sided t tests to examine neural markers of resilience to depression as the main outcomes of interest. Specifically, we assessed differences in connectivity of the limbic (amygdala seed), salience (anterior insula seed), and executive control (dorsolateral prefrontal cortex seed) networks, implicated in emotion regulation. We also examined the association between functional connectivity and life events.Of the 65 participants (mean [SD] age, 18.9 [2.5] years), adolescent females in the resilient group had greater connectivity between the amygdala and orbitofrontal cortex (z score = 0.23; P < .001) and between the dorsolateral prefrontal cortex and frontotemporal regions (z score = 0.24; P < .001) than did converted adolescent females. In adolescent females in the resilient group only, strength of amygdala-orbitofrontal cortex connectivity was correlated with positive life events (r18 = 0.48; P = .03). Resilient adolescent females had greater connectivity within frontal (z score = 0.07; P < .001) and limbic (z score = 0.21; P < .001) networks than did control individuals. Both high-risk groups had greater salience network connectivity: the converted group had greater intranetwork connectivity than did the resilient (z score = 0.13; P < .001) and control (z score = 0.10; P < .001) groups, and the adolescent females in the resilient group had greater salience network connectivity with the superior frontal gyrus than did the converted (z score = 0.24; P < .001) adolescent females.Resilient adolescent females have compensatory functional connectivity patterns in emotion regulatory networks that correlate with positive life events, suggesting that experience-dependent plasticity within these networks may confer resilience to depression. Further studies are warranted concerning connectivity-associated targets for promoting resilience in high-risk individuals.

  View details for PubMedID 29562053

  View details for PubMedCentralID PMC5875355

• Irritability, Externalizing, and Internalizing Psychopathology in Adolescence: Cross-Sectional and Longitudinal Associations and Moderation by Sex. Journal of clinical child and adolescent psychology : the official journal for the Society of Clinical Child and Adolescent Psychology, American Psychological Association, Division 53 Humphreys, K. L., Schouboe, S. N., Kircanski, K., Leibenluft, E., Stringaris, A., Gotlib, I. H. 2018: 1–9

  Abstract

  Irritability is a common feature of many psychiatric disorders, including both externalizing and internalizing disorders. There is little research, however, examining associations between irritability and these symptom domains, particularly during the important developmental period of adolescence, characterized by sex differences in the prevalence of disorders. We examined the cross-sectional associations between irritability, measured with the Affective Reactivity Index, and symptoms of externalizing and internalizing domains of psychopathology, measured with the Youth Self Report, in a volunteer community sample (N = 183) of 9- to 13-year-old (M=11.39, SD=1.07) boys and girls (37% White/Caucasian, 8% Asian, 11% Hispanic, 8% African American, 2% Native American, 2% Pacific Islander, 28% Other, and 3% not reported). A subset of the sample (n=112) provided data at a 2-year follow-up, used to extend these associations. There were no sex differences in levels of irritability; however, the associations between irritability and symptom domains were moderated by sex. Specifically, in girls, irritability was associated equally with externalizing and internalizing symptoms. In contrast, in boys, irritability was associated more strongly with externalizing symptoms than with internalizing symptoms. Thus, across both sexes, irritability was moderately associated with externalizing symptoms, but the association between irritability and internalizing symptoms was stronger in girls than in boys. At follow-up, sex moderated the association between baseline irritability and later externalizing and internalizing symptoms. These findings indicate that irritability is associated with both externalizing and internalizing symptoms in early adolescence and that irritability is associated with internalizing symptoms more strongly in girls than in boys.

  View details for PubMedID 29667523

• Time-varying effects of income on hippocampal volume trajectories in adolescent girls DEVELOPMENTAL COGNITIVE NEUROSCIENCE Ellwood-Lowe, M. E., Humphreys, K. L., Ordaz, S. J., Camacho, M., Sacchet, M. D., Gotlib, I. H. 2018; 30: 41–50

  Abstract

  Children from lower-SES families exhibit smaller hippocampal volume than do their higher-SES peers. Few studies, however, have compared hippocampal developmental trajectories as a function of SES. Thus, it is unclear whether initial rank-order stability is preserved, or whether volumes diverge/converge over the course of adolescence. In a sample of 101 girls ages 10-24 years, we examined the longitudinal association between family income and parental education, proxies for SES, and changes in hippocampal volume. Hippocampal volume was obtained using MRI; using mixed modeling, we examined the effects of income and education on hippocampal volume across age. As expected, changes in volume were non-linear across development. Further, trajectories diverged in mid-adolescence, with lower-income girls exhibiting reductions in hippocampal volume. Maximal income-related differences were observed at 18 years, and trajectories converged thereafter. This interaction remained significant when accounting for maternal hippocampal volume, suggesting a unique contribution of environment over potential heritable differences. In contrast, the association between parental education and offspring hippocampal volume appeared to be stable across adolescence, with higher levels of parental education predicting consistently larger hippocampal volume. These findings constitute preliminary evidence that girls from lower-income homes exhibit unique trajectories of hippocampal growth, with differences most evident in late adolescence.

  View details for PubMedID 29275097

  View details for PubMedCentralID PMC5963716

• Emotional Arousal May Increase Susceptibility to Fraud in Older and Younger Adults Kircanski, K., Notthoff, N., DeLiema, M., Samanez-Larkin, G. R., Shadel, D., Mottola, G., Carstensen, L. L., Gotlib, I. H. AMER PSYCHOLOGICAL ASSOC. 2018: 325–37

  Abstract

  Financial fraud is a societal problem for adults of all ages, but financial losses are especially damaging to older adults who typically live on fixed incomes and have less time to recoup losses. Persuasion tactics used by fraud perpetrators often elicit high levels of emotional arousal; thus, studying emotional arousal may help to identify the conditions under which individuals are particularly susceptible to fraud. We examined whether inducing high-arousal positive (HAP) and high-arousal negative (HAN) emotions increased susceptibility to fraud. Older (ages 65 to 85) and younger (ages 30 to 40) adults were randomly assigned to 1 of 3 emotional arousal conditions in a laboratory task: HAP, HAN, or low arousal (LA). Fraud susceptibility was assessed through participants' responses to misleading advertisements. Both HAP and HAN emotions were successfully induced in older and younger participants. For participants who exhibited the intended induced emotional arousal, both the HAP and HAN conditions, relative to the LA condition, significantly increased participants' reported intention to purchase falsely advertised items. These effects did not differ significantly between older and younger adults and were mitigated in participants who did not exhibit the intended emotional arousal. However, irrespective of the emotional arousal condition to which older adults were assigned (HAP, HAN, or LA), they reported greater purchase intention than did younger adults. These results inform the literature on fraud susceptibility and aging. Educating consumers to postpone financial decisions until they are in calm emotional states may protect against this common persuasion tactic. (PsycINFO Database Record

  View details for PubMedID 29658750

• Network-based approaches to examining stress in the adolescent brain NEUROBIOLOGY OF STRESS Ho, T. C., Dennis, E. L., Thompson, P. M., Gotlib, I. H. 2018; 8: 147–57

  View details for DOI 10.1016/j.ynstr.2018.05.002

  View details for Web of Science ID 000433627600015

• Network-based approaches to examining stress in the adolescent brain. Neurobiology of stress Ho, T. C., Dennis, E. L., Thompson, P. M., Gotlib, I. H. 2018; 8: 147-157

  Abstract

  Exposure to stress, particularly in periods of rapid brain maturation such as adolescence, can profoundly influence developmental processes that undergird the organization of structural and functional brain networks and that may mediate the association between stressful experiences and maladaptive outcomes. While studies in translational developmental neuroscience often focus on how specific brain regions or targeted connections are altered by stress and psychiatric disease, the emerging field of network science may be especially valuable for elucidating the impact of stress on the intricate connectomics of the adolescent brain. Here we review recent studies that use graph theory and other network science approaches to understand normative adolescent brain development, effects of childhood maltreatment on the brain, and disorders characterized by pathological responses to stress in adolescents. Overall, these studies demonstrate that graph theory can be useful in identifying and quantifying developmental processes related to segregation, integration, and localized hub influence that are affected by stress exposure and that may lead to psychopathology. Finally, we discuss limitations in the current application of graph theory in this area and suggest what we believe are important directions for future work.

  View details for DOI 10.1016/j.ynstr.2018.05.002

  View details for PubMedID 29888310

  View details for PubMedCentralID PMC5991327

• Network basis of suicidal ideation in depressed adolescents JOURNAL OF AFFECTIVE DISORDERS Ordaz, S. J., Goyer, M. S., Ho, T. C., Singh, M. K., Gotlib, I. H. 2018; 226: 92–99

  Abstract

  Suicidal ideation rates rise precipitously in adolescence, contributing to risk for attempts. Although researchers are beginning to explore the brain basis of attempts in depressed adolescents, none have focused on the basis of ideation, which has implications for prevention. This study examined the association between intrinsic neural network coherence and the severity of suicidal ideation in depressed adolescents.Forty adolescents diagnosed with Major Depressive Disorder were administered the Columbia-Suicide Severity Rating Scale and underwent resting-state fMRI. We quantified within-network coherence in the executive control (ECN), default mode (DMN), and salience (SN) networks, and in a non-relevant network consisting of noise signal. We associated coherence in each of these networks with the greatest lifetime severity of suicidal ideation experienced, covarying for motion, age of depression onset, and severity of current depressive and anxious symptoms.Lower coherence in the left ECN, anterior DMN, and SN were independently associated with greater lifetime severity of suicidal ideation. When including all three significant networks and covariates in a single model, only the left ECN significantly predicted suicidal ideation.Studies with a larger sample size are needed to verify our findings.Our finding of hypoconnectivity in multiple networks extends emerging evidence for hypoconnectivity in adolescent suicidality and is consistent with theoretical conceptualizations of suicidal ideation as a complex set of cognitions associated with cognitive control, self-referential thinking, and processing salient information. While multiple networks could be targets for effective early interventions, those targeting ECN functionality (cognitive control) may be particularly beneficial.

  View details for PubMedID 28968564

• Corticotropin-releasing factor 1 receptor haplotype and cognitive features of major depression. Translational psychiatry Davis, E. G., Keller, J. n., Hallmayer, J. n., Pankow, H. R., Murphy, G. M., Gotlib, I. H., Schatzberg, A. F. 2018; 8 (1): 5

  Abstract

  Corticotropin-releasing factor signaling through CRF receptor type 1 (CRF1) has been shown to contribute to learning and memory function. A haplotype of alleles T-A-T in a set of common polymorphisms in the gene encoding for CRF1(CRHR1) has been associated with both depression vulnerability and alterations in cognitive functioning. The present study investigated the relations between the TAT haplotype and specific symptoms of depression, self-reported ruminative behaviors, and neuropsychological performance on a learning and memory task. Participants were adults with major depression with and without psychotic features (N = 406). Associations were examined between TAT haplotype and endorsement of depression symptoms from diagnostic interviews, scores on the rumination response scale (RRS), and verbal memory performance on the California Verbal Learning Test-II (CVLT-II). All analyses included depression subtype, age, and sex as covariates; CVLT-II analyses also included evening cortisol levels. Across the entire sample, carriers of more copies of the TAT haplotype reported greater endorsement of the symptom describing difficulty concentrating and making decisions. In separate subsamples, TAT homozygotes had higher rumination scores on the RRS, both brooding and reflection subscales, and more TAT copies were associated with poorer CVLT-II performance in both total learning and free recall trials. These data demonstrate that the CRHR1 TAT haplotype is associated with cognitive features of depression including difficulty with decision-making, higher rumination, and poorer learning and memory. It will be important in future research to identify the specific molecular mechanisms for CRF1signaling that contribute to depression-related cognitive dysfunction.

  View details for PubMedID 29317606

  View details for PubMedCentralID PMC5802461

• The everyday dynamics of rumination and worry: precipitant events and affective consequences COGNITION & EMOTION Kircanski, K., Thompson, R. J., Sorenson, J., Sherdell, L., Gotlib, I. H. 2018; 32 (7): 1424-1436

  View details for DOI 10.1080/02699931.2017.1278679

  View details for Web of Science ID 000450570500004

• Dynamic Functional Connectivity and Individual Differences in Emotions During Social Stress HUMAN BRAIN MAPPING Tobia, M. J., Hayashi, K., Ballard, G., Gotlib, I. H., Waugh, C. E. 2017; 38 (12): 6185–6205

  Abstract

  Exposure to acute stress induces multiple emotional responses, each with their own unique temporal dynamics. Dynamic functional connectivity (dFC) measures the temporal variability of network synchrony and captures individual differences in network neurodynamics. This study investigated the relationship between dFC and individual differences in emotions induced by an acute psychosocial stressor. Sixteen healthy adult women underwent fMRI scanning during a social evaluative threat (SET) task, and retrospectively completed questionnaires that assessed individual differences in subjectively experienced positive and negative emotions about stress and stress relief during the task. Group dFC was decomposed with parallel factor analysis (PARAFAC) into 10 components, each with a temporal signature, spatial network of functionally connected regions, and vector of participant loadings that captures individual differences in dFC. Participant loadings of two networks were positively correlated with stress-related emotions, indicating the existence of networks for positive and negative emotions. The emotion-related networks involved the ventromedial prefrontal cortex, cingulate cortex, anterior insula, and amygdala, among other distributed brain regions, and time signatures for these emotion-related networks were uncorrelated. These findings demonstrate that individual differences in stress-induced positive and negative emotions are each uniquely associated with large-scale brain networks, and suggest that dFC is a mechanism that generates individual differences in the emotional components of the stress response. Hum Brain Mapp 38:6185-6205, 2017. © 2017 Wiley Periodicals, Inc.

  View details for PubMedID 28940859

• The association between early life stress and prefrontal cortex activation during implicit emotion regulation is moderated by sex in early adolescence DEVELOPMENT AND PSYCHOPATHOLOGY Colich, N. L., Williams, E. S., Ho, T. C., King, L. S., Humphreys, K. L., Price, A. N., Ordaz, S. J., Gotlib, I. H. 2017; 29 (5): 1851–64

  Abstract

  Early life stress (ELS) is a significant risk factor for the emergence of internalizing problems in adolescence. Beginning in adolescence, females are twice as likely as males to experience internalizing disorders. The present study was designed to examine sex differences in the association between ELS and internalizing problems in early pubertal adolescents, and whether and how corticolimbic function and connectivity may underlie these associations. Fifty-nine early pubertal males and 78 early pubertal females, ages 9-13 years (all Tanner Stage 3 or below) underwent functional magnetic resonance imaging as they performed an emotion label task that robustly interrogates corticolimbic function. Participants were also interviewed about their experience of ELS. Females exhibited a positive association between ELS and internalizing problems, whereas males exhibited no such association. Whole-brain and amygdala region of interest analyses indicated that whereas females exhibited a positive association between ELS and the ventrolateral prefrontal cortex during implicit emotion regulation, males showed no such association. Activation in these regions was positively associated with internalizing problems in females but not males; however, activation in these regions did not mediate the association between ELS and internalizing problems. Finally, both boys and girls exhibited an association between ELS and increased negative connectivity between the right ventrolateral prefrontal cortex and bilateral amygdala. Using a carefully characterized sample of early pubertal adolescents, the current study highlights important sex differences in the development of corticolimbic circuitry during a critical period of brain development. These sex differences may play a significant role in subsequent risk for internalizing problems.

  View details for PubMedID 29162186

  View details for PubMedCentralID PMC5726300

• Fractional Anisotropy in the Frontal Segment of the Uncinate Fasciculus in Adolescents at Risk for Depression Ho, T., Nimarko, A., Oskirko, K., Leong, J., Ordaz, S., Gotlib, I. NATURE PUBLISHING GROUP. 2017: S496–S497

  View details for Web of Science ID 000416846303033

• Neural Correlates of Impaired Removal of Negative Information From Working Memory are Associated With Rumination and Reappraisal in Individuals Diagnosed With Major Depressive Disorder Davis, E., Uncapher, M., Camacho, M., Sacchet, M., Wagner, A., Gotlib, I. NATURE PUBLISHING GROUP. 2017: S562–S563

  View details for Web of Science ID 000416846303135

• Looking at the Brighter Side: Functional Connectivity Biomarkers of Resilience to Adolescent Depression in Emotion Regulation Networks Fischer, A., Camacho, M., Ho, T., Whitfield-Gabrieli, S., Gotlib, I. NATURE PUBLISHING GROUP. 2017: S501

  View details for Web of Science ID 000416846303040

• Positive and Negative Affective Forecasting in Remitted Individuals with Bipolar I Disorder, and Major Depressive Disorder, and Healthy Controls COGNITIVE THERAPY AND RESEARCH Thompson, R. J., Spectre, A., Insel, P. S., Mennin, D., Gotlib, I. H., Gruber, J. 2017; 41 (5): 673–85

  View details for DOI 10.1007/s10608-017-9840-2

  View details for Web of Science ID 000409958700001

• Machine Learning for Large-Scale Quality Control of 3D Shape Models in Neuroimaging. Machine learning in medical imaging. MLMI (Workshop) Petrov, D., Gutman, B. A., Yu, S. J., van Erp, T. G., Turner, J. A., Schmaal, L., Veltman, D., Wang, L., Alpert, K., Isaev, D., Zavaliangos-Petropulu, A., Ching, C. R., Calhoun, V., Glahn, D., Satterthwaite, T. D., Andreasen, O. A., Borgwardt, S., Howells, F., Groenewold, N., Voineskos, A., Radua, J., Potkin, S. G., Crespo-Facorro, B., Tordesillas-Gutierrez, D., Shen, L., Lebedeva, I., Spalletta, G., Donohoe, G., Kochunov, P., Rosa, P. G., James, A., Dannlowski, U., Baune, B. T., Aleman, A., Gotlib, I. H., Walter, H., Walter, M., Soares, J. C., Ehrlich, S., Gur, R. C., Doan, N. T., Agartz, I., Westlye, L. T., Harrisberger, F., Riecher-Rossler, A., Uhlmann, A., Stein, D. J., Dickie, E. W., Pomarol-Clotet, E., Fuentes-Claramonte, P., Canales-Rodriguez, E. J., Salvador, R., Huang, A. J., Roiz-Santianez, R., Cong, S., Tomyshev, A., Piras, F., Vecchio, D., Banaj, N., Ciullo, V., Hong, E., Busatto, G., Zanetti, M. V., Serpa, M. H., Cervenka, S., Kelly, S., Grotegerd, D., Sacchet, M. D., Veer, I. M., Li, M., Wu, M., Irungu, B., Walton, E., Thompson, P. M. 2017; 10541: 371–78

  Abstract

  As very large studies of complex neuroimaging phenotypes become more common, human quality assessment of MRI-derived data remains one of the last major bottlenecks. Few attempts have so far been made to address this issue with machine learning. In this work, we optimize predictive models of quality for meshes representing deep brain structure shapes. We use standard vertex-wise and global shape features computed homologously across 19 cohorts and over 7500 human-rated subjects, training kernelized Support Vector Machine and Gradient Boosted Decision Trees classifiers to detect meshes of failing quality. Our models generalize across datasets and diseases, reducing human workload by 30-70%, or equivalently hundreds of human rater hours for datasets of comparable size, with recall rates approaching inter-rater reliability.

  View details for PubMedID 30035274

• Hyperactivation in Cognitive Control and Visual Attention Brain Regions During Emotional Interference in Adolescent Depression. Biological psychiatry. Cognitive neuroscience and neuroimaging Colich, N. L., Ho, T. C., Foland-Ross, L. C., Eggleston, C., Ordaz, S. J., Singh, M. K., Gotlib, I. H. 2017; 2 (5): 388-395

  Abstract

  Individuals with Major Depressive Disorder (MDD) are characterized by biases in attention to negative emotional material. While there is evidence that anomalous functioning in frontocingulate regions may underlie these biases, we know little about the neural correlates of negative emotional biases in depressed adolescents.Eighteen adolescents diagnosed with MDD and 21 matched healthy control (CTL) adolescents underwent fMRI while performing an emotional distractor task. On each trial participants were presented with task-relevant house pairs and task-irrelevant face pairs. Participants indicated whether the house pairs were identical while ignoring the face pairs, which were either fearful, sad, or neutral.Despite equivalent behavioral performance (response time and accuracy) between groups, adolescents with MDD exhibited greater activation in frontocingulate regions, including dorsal anterior cingulate cortex (dACC) and inferior frontal gyrus/middle frontal gyrus (IFG/MFG), and occipitoparietal regions, including lateral occipital cortex and superior parietal lobule when ignoring fearful versus neutral faces. Response times to these trial conditions also correlated negatively with activation in IFG/MFG and lateral occipital cortex suggesting these regions are recruited in order to effectively ignore emotional distractors. Groups did not differ when ignoring sad versus neutral faces or fearful versus sad faces.Adolescents with MDD recruit both cognitive control and visual attention regions to a greater degree than do CTL adolescents, reflecting greater cognitive demand when downregulating threat-related stimuli.

  View details for DOI 10.1016/j.bpsc.2016.09.001

  View details for PubMedID 28890942

  View details for PubMedCentralID PMC5586219

• Cortical abnormalities in adults and adolescents with major depression based on brain scans from 20 cohorts worldwide in the ENIGMA Major Depressive Disorder Working Group MOLECULAR PSYCHIATRY Schmaal, L., Hibar, D. P., Saemann, P. G., Hall, G. B., Baune, B. T., Jahanshad, N., Cheung, J. W., van Erp, T. G., Bos, D., Ikram, M. A., Vernooij, M. W., Niessen, W. J., Tiemeier, H., Hofman, A., Wittfeld, K., Grabe, H. J., Janowitz, D., Buelow, R., Selonke, M., Voelzke, H., Grotegerd, D., Dannlowski, U., Arolt, V., Opel, N., Heindel, W., Kugel, H., Hoehn, D., Czisch, M., Couvy-Duchesne, B., Renteria, M. E., Strike, L. T., Wright, M. J., MILLS, N. T., de Zubicaray, G. I., McMahon, K. L., Medland, S. E., Martin, N. G., Gillespie, N. A., Goya-Maldonado, R., Gruber, O., Kraemer, B., Hatton, S. N., Lagopoulos, J., Hickie, I. B., Frodl, T., Carballedo, A., Frey, E. M., Van Velzen, L. S., Penninx, B. W., van Tol, M., Van der Wee, N. J., DAVEY, C. G., Harrison, B. J., Mwangi, B., Cao, B., Soares, J. C., Veer, I. M., Walter, H., Schoepf, D., Zurowski, B., Konrad, C., Schramm, E., Normann, C., Schnell, K., Sacchet, M. D., Gotlib, I. H., MacQueen, G. M., Godlewska, B. R., Nickson, T., McIntosh, A. M., Papmeyer, M., Whalley, H. C., Hall, J., Sussmann, J. E., Li, M., Walter, M., Aftanas, L., Brack, I., Bokhan, N. A., Thompson, P. M., Veltman, D. J. 2017; 22 (6): 900-909

  Abstract

  The neuro-anatomical substrates of major depressive disorder (MDD) are still not well understood, despite many neuroimaging studies over the past few decades. Here we present the largest ever worldwide study by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Major Depressive Disorder Working Group on cortical structural alterations in MDD. Structural T1-weighted brain magnetic resonance imaging (MRI) scans from 2148 MDD patients and 7957 healthy controls were analysed with harmonized protocols at 20 sites around the world. To detect consistent effects of MDD and its modulators on cortical thickness and surface area estimates derived from MRI, statistical effects from sites were meta-analysed separately for adults and adolescents. Adults with MDD had thinner cortical gray matter than controls in the orbitofrontal cortex (OFC), anterior and posterior cingulate, insula and temporal lobes (Cohen's d effect sizes: -0.10 to -0.14). These effects were most pronounced in first episode and adult-onset patients (>21 years). Compared to matched controls, adolescents with MDD had lower total surface area (but no differences in cortical thickness) and regional reductions in frontal regions (medial OFC and superior frontal gyrus) and primary and higher-order visual, somatosensory and motor areas (d: -0.26 to -0.57). The strongest effects were found in recurrent adolescent patients. This highly powered global effort to identify consistent brain abnormalities showed widespread cortical alterations in MDD patients as compared to controls and suggests that MDD may impact brain structure in a highly dynamic way, with different patterns of alterations at different stages of life.Molecular Psychiatry advance online publication, 3 May 2016; doi:10.1038/mp.2016.60.

  View details for DOI 10.1038/mp.2016.60

  View details for Web of Science ID 000401702800013

• Like Mother Like Daughter: Putamen Activation as a Mechanism Underlying Intergenerational Risk for Depression. Social cognitive and affective neuroscience Colich, N. L., Ho, T. C., Ellwood-Lowe, M., Foland-Ross, L. C., Sacchet, M. D., LeMoult, J. L., Gotlib, I. H. 2017

  Abstract

  Having a depressed mother is one of the strongest predictors for developing depression in adolescence. Given the role of aberrant reward processing in the onset and maintenance of depression, we examined the association between mothers' and their daughters' neural response to the anticipation of reward and loss. Fifteen non-depressed mothers with a history of recurrent depression and their never-disordered daughters, and 23 mothers without past or current depression and their never-disordered daughters, underwent fMRI while performing the monetary incentive delay (MID) task. To assess mother-daughter concordance, we first identified ROIs involved in the anticipation of reward and loss across all mother-daughter pairs. Within each of these ROIs, we examined the association between mothers' and daughters' neural response, and the interaction between group status and mothers' neural response in predicting daughters' neural response. We found a significant association between mothers' and daughters' putamen response to the anticipation of loss, regardless of mother's depression history. Furthermore, pubertal stage moderated the association between mother-daughter putamen concordance. Our findings suggest a unique role of the putamen in the maternal transmission of reward learning and have important implications for understanding disorders characterized by disturbances in reward learning and processing, such as major depression.

  View details for DOI 10.1093/scan/nsx073

  View details for PubMedID 28575505

• Inflexible Functional Connectivity of the Dorsal Anterior Cingulate Cortex in Adolescent Major Depressive Disorder. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology Ho, T. C., Sacchet, M. D., Connolly, C. G., Margulies, D. S., Tymofiyeva, O., Paulus, M. P., Simmons, A. N., Gotlib, I. H., Yang, T. T. 2017

  Abstract

  Recent evidence suggests that anterior cingulate cortex (ACC) maturation during adolescence contributes to or underlies the development of major depressive disorder (MDD) during this sensitive period. The ACC is a structure that sits at the intersection of several task-positive networks (eg, central executive network, CEN) which are still developing during adolescence. While recent work using seed-based approaches indicate that depressed adolescents show limited task-evoked versus resting-state connectivity (termed 'inflexibility') between the ACC and task-negative networks, no study has used network-based approaches to investigate inflexibility of the ACC in task-positive networks to understand adolescent MDD. Here, we used graph theory to compare flexibility of network-level topology in eight subregions of the ACC (spanning three task-positive networks) in 42 unmedicated adolescents with MDD and 53 well-matched healthy controls. All participants underwent fMRI scanning during resting-state and a response inhibition task that robustly engages task-positive networks. Relative to controls, depressed adolescents were characterized by inflexibility in local efficiency of a key ACC node in the CEN: right dorsal anterior cingulate cortex/medial frontal gyrus (R dACC/MFG). Furthermore, individual differences in flexibility of local efficiency of R dACC/MFG significantly predicted inhibition performance, consistent with current literature demonstrating that flexible network organization affords successful cognitive control. Finally, reduced local efficiency of dACC/MFG during the task was significantly associated with an earlier age of depression onset, consistent with prior work suggesting that MDD may alter functional network development. Our results support a neurodevelopmental hypothesis of MDD wherein dysfunctional self-regulation is potentially reflected by altered ACC maturation.Neuropsychopharmacology accepted article preview online, 29 May 2017. doi:10.1038/npp.2017.103.

  View details for DOI 10.1038/npp.2017.103

  View details for PubMedID 28553837

• Myelination of the brain in Major Depressive Disorder: An in vivo quantitative magnetic resonance imaging study SCIENTIFIC REPORTS Sacchet, M. D., Gotlib, I. H. 2017; 7

  Abstract

  Evidence from post-mortem, genetic, neuroimaging, and non-human animal research suggests that Major Depressive Disorder (MDD) is associated with abnormalities in brain myelin content. Brain regions implicated in this research, and in MDD more generally, include the nucleus accumbens (NAcc), lateral prefrontal cortex (LPFC), insula, subgenual anterior cingulate cortex (sgACC), and medial prefrontal cortex (mPFC). We examined whether MDD is characterized by reduced myelin at the whole-brain level and in NAcc, LPFC, insula, sgACC, and mPFC. Quantitative magnetic resonance imaging (qMRI) permits the assessment of myelin content, in vivo, in the human brain through the measure of R1. In this study we used qMRI to measure R1 in 40 MDD and 40 healthy control (CTL) participants. We found that the MDD participants had lower levels of myelin than did the CTL participants at the whole-brain level and in the NAcc, and that myelin in the LPFC was reduced in MDD participants who had experienced a greater number of depressive episodes. Although further research is needed to elucidate the role of myelin in affecting emotional, cognitive, behavioral, and clinical aspects of MDD, the current study provides important new evidence that a fundamental property of brain composition, myelin, is altered in this disorder.

  View details for DOI 10.1038/s41598-017-02062-y

  View details for Web of Science ID 000401614900058

  View details for PubMedID 28526817

• Perceived Social Standing Predicts Hippocampal Volume over and above the Effects of Income Ellwood-Lowe, M., Humphreys, K., Sacchet, M., Camacho, M., Ordaz, S., Gotlib, I. ELSEVIER SCIENCE INC. 2017: S188

  View details for DOI 10.1016/j.biopsych.2017.02.945

  View details for Web of Science ID 000400348700458

• Association of CRHR1 TAT Haplotype with Cognitive Features of Major Depressive Disorder Davis, E., Keller, J., Hallmayer, J., Ryan, H., Murphy, G., Gotlib, I., Schatzberg, A. ELSEVIER SCIENCE INC. 2017: S225–S226

  View details for DOI 10.1016/j.biopsych.2017.02.1166

  View details for Web of Science ID 000400348700555

• Depression in Men and Women One Year Following Traumatic Brain Injury (TBI): A TBI Model Systems Study FRONTIERS IN PSYCHOLOGY Lavoie, S., Sechrist, S., Quach, N., Ehsanian, R., Duong, T., Gotlib, I. H., Isaac, L. 2017; 8

  Abstract

  In the general population, females experience depression at significantly higher rates than males. Individuals with traumatic brain injury (TBI) are at substantially greater risk for depression compared to the overall population. Treatment of, and recovery from, TBI can be hindered by depression; comorbid TBI and depression can lead to adverse outcomes and negatively affect multiple aspects of individuals' lives. Gender differences in depression following TBI are not well understood, and relevant empirical findings have been mixed. Utilizing the Patient Health Questionnaire-9 (PHQ-9) 1 year after TBI, we examined whether women would experience more severe depressive symptoms, and would endorse higher levels of depression within each category of depression severity, than would men. Interestingly, and contrary to our hypothesis, men and women reported mild depression at equal rates; PHQ-9 total scores were slightly lower in women than in men. Men and women did not differ significantly in any PHQ-9 depression severity category. Item analyses, yielded significant gender differences on the following items: greater concentration difficulties (cognitive problems) in men and more sleep disturbances (psychosomatic issues) in women per uncorrected two-sample Z-test for proportions analyses; however, these results were not significant after the family-wise Bonferroni correction. Our results indicate that, in contrast to the general population, mild depression in persons with moderate to severe TBI may not be gender-specific. These findings underscore the need for early identification, active screening, and depression treatment equally for men and women to improve emotional well-being, promote recovery, and enhance quality of life following TBI.

  View details for DOI 10.3389/fpsyg.2017.00634

  View details for Web of Science ID 000401186500001

  View details for PubMedID 28529492

• The neuroscience of depression: Implications for assessment and intervention (vol 62, pg 60, 2014) BEHAVIOUR RESEARCH AND THERAPY Singh, M. K., Gotlib, I. H. 2017; 92: 106

  View details for PubMedID 28342540

• Effects of Sensitivity to Life Stress on Uncinate Fasciculus Segments in Early Adolescence. Social cognitive and affective neuroscience Ho, T. C., King, L. S., Leong, J. K., Colich, N. L., Humphreys, K. L., Ordaz, S. J., Gotlib, I. H. 2017

  Abstract

  Previous research suggests that exposure to early life stress (ELS) affects the structural integrity of the uncinate fasciculus (UF), a frontolimbic white matter tract that undergoes protracted development throughout adolescence. Adolescence is an important transitional period characterized by the emergence of internalizing psychopathology such as anxiety, particularly in individuals with high levels of stress sensitivity. We examined the relations among sensitivity to ELS, structural integrity of the UF, and anxiety symptoms in 104 early adolescents. We conducted structured interviews to assess exposure to ELS and obtained subjective and objective ratings of stress severity, from which we derived an index of ELS sensitivity. We also acquired diffusion MRI and conducted deterministic tractography to visualize UF trajectories and to compute measures of structural integrity from three distinct segments of the UF: frontal, insular, temporal. We found that higher sensitivity to ELS predicted both reduced fractional anisotropy in right frontal UF and higher levels of anxiety symptoms. These findings suggest that fibers in frontal UF, which are still developing throughout adolescence, are most vulnerable to the effects of heightened sensitivity to ELS, and that reduced structural integrity of frontal UF may underlie the relation between early stress and subsequent internalizing psychopathology.

  View details for DOI 10.1093/scan/nsx065

  View details for PubMedID 28460088

• GABA editing with macromolecule suppression using an improved MEGA-SPECIAL sequence. Magnetic resonance in medicine Gu, M., Hurd, R., Noeske, R., Baltusis, L., Hancock, R., Sacchet, M. D., Gotlib, I. H., Chin, F. T., Spielman, D. M. 2017

  Abstract

  The most common γ-aminobutyric-acid (GABA) editing approach, MEGA-PRESS, uses J-editing to measure GABA distinct from larger overlapping metabolites, but suffers contamination from coedited macromolecules (MMs) comprising 40 to 60% of the observed signal. MEGA-SPECIAL is an alternative method with better MM suppression, but is not widely used primarily because of its relatively poor spatial localization. Our goal was to develop an improved MM-suppressed GABA editing sequence at 3 Tesla.We modified a single-voxel MEGA-SPECIAL sequence with an oscillating readout gradient for improved spatial localization, and used very selective 30-ms editing pulses for improved suppression of coedited MMs.Simulation and in vivo experiments confirmed excellent MM suppression, insensitive to the range of B0 frequency drifts typically encountered in vivo. Both intersubject and intrasubject studies showed that MMs, when suppressed by the improved MEGA-SPECIAL method, contributed approximately 40% to the corresponding MEGA-PRESS measurements. From the intersubject study, the coefficient of variation for GABA+/Cre (MEGA-PRESS) was 11.2% versus 7% for GABA/Cre (improved MEGA-SPECIAL), demonstrating significantly reduced variance (P = 0.005), likely coming from coedited MMs.This improved MEGA-SPECIAL sequence provides unbiased GABA measurements with reduced variance as compared with conventional MEGA-PRESS. This approach is also relatively insensitive to the range of B0 drifts typically observed in in vivo human studies. Magn Reson Med, 2017. © 2017 International Society for Magnetic Resonance in Medicine.

  View details for DOI 10.1002/mrm.26691

  View details for PubMedID 28370458

• Interpretation Bias Training in Depressed Adolescents: Near- and Far-Transfer Effects. Journal of abnormal child psychology LeMoult, J., Colich, N., Joormann, J., Singh, M. K., Eggleston, C., Gotlib, I. H. 2017

  Abstract

  Depressed adolescents are characterized by negative interpretation biases. Although investigators have used cognitive bias modification for interpretation (CBM-I) to experimentally manipulate interpretation biases in depressed adults, the near- and far-transfer effects are not well understood in adolescents diagnosed with Major Depressive Disorder (MDD). In this study, we extend previous research by investigating the near- and far-transfer effects of 6 sessions of Positive versus Neutral CBM-I on independent measures of interpretation bias (near-transfer effects) and on attention biases and clinical symptoms (far-transfer effects) in a sample of adolescents with MDD (n = 46). At post-training, adolescents who received Positive CBM-I interpreted ambiguous scenarios more positively than did participants who received Neutral CBM-I, providing evidence of training effectiveness. There was no evidence, however, of near- or far-transfer effects. These findings raise concerns about the malleability of interpretation biases in adolescent depression and suggest that further work is needed to establish the clinical utility of CBM-I for adolescents with MDD.

  View details for DOI 10.1007/s10802-017-0285-6

  View details for PubMedID 28299526

• The impact of the severity of early life stress on diurnal cortisol: The role of puberty. Psychoneuroendocrinology King, L. S., Colich, N. L., LeMoult, J., Humphreys, K. L., Ordaz, S. J., Price, A. N., Gotlib, I. H. 2017; 77: 68-74

  Abstract

  Researchers have documented dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis in children and adolescents who experienced early life stress (ELS). The precise nature of this dysregulation, however, has been difficult to discern. In fact, both elevated and blunted patterns of diurnal cortisol regulation have been reported in children and adolescents exposed to greater ELS, including both reduced and heightened cortisol levels and change in cortisol across the day. These divergent findings may be due to developmental changes in the relation between ELS and HPA-axis functioning. The present study was designed to examine the role of puberty in the impact of the severity of ELS on the regulation of diurnal cortisol. Boys and girls (N=145) ages 9-13 years recruited from lower-risk communities completed an interview about their ELS experiences and at-home collection of diurnal cortisol. ELS experiences were objectively coded for severity, and children's level of pubertal development was measured using Tanner Staging. Multi-level piecewise mixed-effects models tested the effects of ELS severity and pubertal stage on cortisol levels at waking, the cortisol awakening response (CAR), and the daytime cortisol slope. While we found no significant interactive effects of pubertal stage and ELS severity on cortisol levels at waking or the daytime cortisol slope, findings indicated that pubertal stage interacted with ELS severity to predict the cortisol awakening response (CAR). Specifically, in earlier puberty, higher ELS was associated with a blunted CAR compared to lower ELS; in contrast, in later puberty, higher ELS was associated with a heightened CAR compared to lower ELS. Differences in the relation between ELS severity and the CAR were uniquely determined by puberty, and not by age. By considering and examining the role of puberty, the current study provides a developmental explanation for previous divergent findings of both blunted and heightened patterns of diurnal cortisol following ELS. These results indicate that careful attention should be given to children's pubertal status before drawing conclusions concerning the nature of diurnal cortisol dysregulation.

  View details for DOI 10.1016/j.psyneuen.2016.11.024

  View details for PubMedID 28024271

  View details for PubMedCentralID PMC5336485

• ADAPTIVE COPING MEDIATES THE RELATION BETWEEN MOTHERS' AND DAUGHTERS' DEPRESSIVE SYMPTOMS: A MODERATED MEDIATION STUDY JOURNAL OF SOCIAL AND CLINICAL PSYCHOLOGY Thompson, R. J., Mata, J., Gershon, A., Gotlib, I. H. 2017; 36 (3): 171-195

  View details for Web of Science ID 000397422600001

• Anticipatory and consummatory pleasure and displeasure in major depressive disorder: An experience sampling study. Journal of abnormal psychology Wu, H., Mata, J., Furman, D. J., Whitmer, A. J., Gotlib, I. H., Thompson, R. J. 2017; 126 (2): 149-159

  Abstract

  Pleasure and displeasure can be parsed into anticipatory and consummatory phases. However, research on pleasure and displeasure in major depressive disorder (MDD), a disorder characterized by anhedonia, has largely focused on deficits in the consummatory phase. Moreover, most studies in this area have been laboratory-based, raising the question of how component processes of pleasure and displeasure are experienced in the daily lives of depressed individuals. Using experience sampling, we compared anticipatory and consummatory pleasure and displeasure for daily activities reported by adults with MDD (n = 41) and healthy controls (n = 39). Participants carried electronic devices for one week and were randomly prompted eight times a day to answer questions about activities to which they most and least looked forward. Compared to healthy controls, MDD participants reported blunted levels of both anticipatory and consummatory pleasure and elevated levels of both anticipatory and consummatory displeasure for daily activities. Independent of MDD status, participants accurately predicted pleasure but overestimated displeasure. These results are the first to provide evidence that, across both anticipatory and consummatory phases, individuals with MDD experience blunted pleasure and elevated displeasure for daily activities. Our findings clarify the disturbances in pleasure and displeasure that characterize MDD and may inform treatment for this debilitating disorder. (PsycINFO Database Record

  View details for DOI 10.1037/abn0000244

  View details for PubMedID 27936838

  View details for PubMedCentralID PMC5305427

• Cognitive and neural consequences of memory suppression in major depressive disorder COGNITIVE AFFECTIVE & BEHAVIORAL NEUROSCIENCE Sacchet, M. D., Levy, B. J., Hamilton, J. P., Maksimovskiy, A., Hertel, P. T., Joormann, J., Anderson, M. C., Wagner, A. D., Gotlib, I. H. 2017; 17 (1): 77-93

  Abstract

  Negative biases in cognition have been documented consistently in major depressive disorder (MDD), including difficulties in the ability to control the processing of negative material. Although negative information-processing biases have been studied using both behavioral and neuroimaging paradigms, relatively little research has been conducted examining the difficulties of depressed persons with inhibiting the retrieval of negative information from long-term memory. In this study, we used the think/no-think paradigm and functional magnetic resonance imaging to assess the cognitive and neural consequences of memory suppression in individuals diagnosed with depression and in healthy controls. The participants showed typical behavioral forgetting effects, but contrary to our hypotheses, there were no differences between the depressed and nondepressed participants or between neutral and negative memories. Relative to controls, depressed individuals exhibited greater activity in right middle frontal gyrus during memory suppression, regardless of the valence of the suppressed stimuli, and differential activity in the amygdala and hippocampus during memory suppression involving negatively valenced stimuli. These findings indicate that depressed individuals are characterized by neural anomalies during the suppression of long-term memories, increasing our understanding of the brain bases of negative cognitive biases in MDD.

  View details for DOI 10.3758/s13415-016-0464-x

  View details for Web of Science ID 000393772800004

• Ruminative brooding is associated with salience network coherence in early pubertal youth SOCIAL COGNITIVE AND AFFECTIVE NEUROSCIENCE Ordaz, S. J., LeMoult, J., Colich, N. L., Prasad, G., Pollak, M., Popolizio, M., Price, A., Greicius, M., Gotlib, I. H. 2017; 12 (2): 298-310

  Abstract

  Rumination, and particularly ruminative brooding, perpetuates dysphoric mood states and contributes to the emergence of depression. Studies of adults and older adolescents have characterized the association between rumination and intrinsic functional connectivity within default mode (DMN), salience (SN) and executive control (ECN) networks; we know little, however, about the brain network basis of rumination during early puberty, a sensitive period for network reorganization. 112 early puberty boys and girls completed resting-state scans, the Ruminative Response Scale, and the Youth Self-Report questionnaire. Using independent components analysis and dual regression, we quantified coherence for each individual in networks of interest (SN, ECN, DMN) and in non-relevant networks (motor, visual) in which we predicted no correlations with behavioral measures. Boys and girls did not differ in levels of rumination or internalizing symptoms, or in coherence for any network. The relation between SN network coherence and rumination; however, and specifically ruminative brooding, was moderated by sex: greater SN coherence was associated with higher levels of brooding in girls but not in boys. Further, in girls, brooding mediated the relation between SN coherence and internalizing symptoms. These results point to coherence within the SN as a potential neurodevelopmental marker of risk for depression in early pubertal girls.

  View details for DOI 10.1093/scan/nsw133

  View details for Web of Science ID 000397312200011

  View details for PubMedCentralID PMC5390708

• The everyday dynamics of rumination and worry: precipitant events and affective consequences. Cognition & emotion Kircanski, K., Thompson, R. J., Sorenson, J., Sherdell, L., Gotlib, I. H. 2017: 1-13

  Abstract

  Rumination and worry are two perseverative, negatively valenced thought processes that characterise depressive and anxiety disorders. Despite significant research interest, little is known about the everyday precipitants and consequences of rumination and worry. Using an experience sampling methodology, we examined and compared rumination and worry with respect to their relations to daily events and affective experience. Participants diagnosed with Major Depressive Disorder (MDD), Generalized Anxiety Disorder (GAD), co-occurring MDD-GAD, or no diagnosis carried an electronic device for one week and reported on rumination, worry, significant events, positive affect (PA), and negative affect (NA). Across the clinical groups, occurrences of everyday events predicted subsequent increases in rumination, but not worry. Further, higher momentary levels of rumination, but not worry, predicted subsequent decreases in PA and increases in NA. Thus, in these clinical groups, rumination was more susceptible to daily events and produced stronger affective changes over time. We discuss implications for theory and clinical intervention.

  View details for DOI 10.1080/02699931.2017.1278679

  View details for PubMedID 28103761

• Emotional variability and clarity in depression and social anxiety. Cognition & emotion Thompson, R. J., Boden, M. T., Gotlib, I. H. 2017; 31 (1): 98-108

  Abstract

  Recent research has underscored the importance of elucidating specific patterns of emotion that characterise mental disorders. We examined two emotion traits, emotional variability and emotional clarity, in relation to both categorical (diagnostic interview) and dimensional (self-report) measures of major depressive disorder (MDD) and social anxiety disorder (SAD) in women diagnosed with MDD only (n = 35), SAD only (n = 31), MDD and SAD (n = 26) or no psychiatric disorder (n = 38). Results of the categorical analyses suggest that elevated emotional variability and diminished emotional clarity are transdiagnostic of MDD and SAD. More specifically, emotional variability was elevated for MDD and SAD diagnoses compared to no diagnosis, showing an additive effect for co-occurring MDD and SAD. Similarly diminished levels of emotional clarity characterised all three clinical groups compared to the healthy control group. Dimensional findings suggest that although emotional variability is associated more consistently with depression than with social anxiety, emotional clarity is associated more consistently with social anxiety than with depression. Results are interpreted using a threshold and dose-response framework.

  View details for PubMedID 26371579

• Large-scale classification of major depressive disorder via distributed Lasso Zhu, D., Li, Q., Riedel, B. C., Jahanshad, N., Hibar, D. P., Veer, I. M., Walter, H., Schmaal, L., Veltman, D. J., Grotegerd, D., Dannlowski, U., Sacchet, M. D., Gotlib, I. H., Ye, J., Thompson, P. M., Romero, E., Lepore, N., Brieva, J., Larrabide SPIE-INT SOC OPTICAL ENGINEERING. 2017

  View details for DOI 10.1117/12.2256935

  View details for Web of Science ID 000399332700034

• Hyperactivation in cognitive control and visual attention brain regions during emotional interference in adolescent depression Biological Psychiatry: Cognitive Neuroscience and Neuroimaging Colich, N., Ho, T., Foland-Ross, L., Eggleston, C., Ordaz, S., Singh, M., Gotlib, I. 2017

  View details for DOI 10.1016/j.bpsc.2016.09.001

• Negative Self-Referential Processing Predicts the Recurrence of Major Depressive Episodes. Clinical psychological science : a journal of the Association for Psychological Science LeMoult, J., Kircanski, K., Prasad, G., Gotlib, I. H. 2017; 5 (1): 174-181

  Abstract

  Most individuals who develop Major Depressive Disorder (MDD) will experience a recurrent depressive episode; we know little, however, about cognitive mechanisms that increase the likelihood of recurrence. In the current study we examined whether negatively biased self-referential processing, negative life events, baseline depressive symptoms, and psychotropic medication use predicted the onset of a subsequent depressive episode in a longitudinal study of women with a history of recurrent MDD. Higher levels of depressive symptoms at baseline predicted experiencing a greater number of negative life events which, in turn, tended to predict recurrence of depression. Importantly, after accounting for other associations, negatively biased self-referential processing contributed unique variance to the likelihood of experiencing a depressive episode over the next three years. Thus, negatively biased self-referential processing appears to be a significant risk factor for the recurrence of depressive episodes and may be an important target for interventions aimed at preventing future episodes.

  View details for DOI 10.1177/2167702616654898

  View details for PubMedID 28286705

• Dynamic functional connectivity of neurocognitive networks in children HUMAN BRAIN MAPPING Marusak, H. A., Calhoun, V. D., Brown, S., Crespo, L. M., Sala-Hamrick, K., Gotlib, I. H., Thomason, M. E. 2017; 38 (1): 97-108

  Abstract

  The human brain is highly dynamic, supporting a remarkable range of cognitive abilities that emerge over the course of development. While flexible and dynamic coordination between neural systems is firmly established for children, our understanding of brain functional organization in early life has been built largely on the implicit assumption that functional connectivity (FC) is static. Understanding the nature of dynamic neural interactions during development is a critical issue for cognitive neuroscience, with implications for neurodevelopmental pathologies that involve anomalies in brain connectivity. In this work, FC dynamics of neurocognitive networks in a sample of 146 youth from varied sociodemographic backgrounds were delineated. Independent component analysis, sliding time window correlation, and k-means clustering were applied to resting-state fMRI data. Results revealed six dynamic FC states that re-occur over time and that complement, but significantly extend, measures of static FC. Moreover, the occurrence and amount of time spent in specific FC states are related to the content of self-generated thought during the scan. Additionally, some connections are more variable over time than are others, including those between inferior parietal lobe and precuneus. These regions contribute to multiple networks and likely play a role in adaptive processes in childhood. Age-related increases in temporal variability of FC among neurocognitive networks were also found. Taken together, these findings lay the groundwork for understanding how variation in the developing chronnectome is related to risk for neurodevelopmental disorders. Understanding how brain systems reconfigure with development should provide insight into the ontogeny of complex, flexible cognitive processes. Hum Brain Mapp 38:97-108, 2017. © 2016 Wiley Periodicals, Inc.

  View details for DOI 10.1002/hbm.23346

  View details for Web of Science ID 000390259700008

  View details for PubMedID 27534733

• Accelerated aging of the putamen in patients with major depressive disorder. Journal of psychiatry & neuroscience Sacchet, M. D., Camacho, M. C., Livermore, E. E., Thomas, E. A., Gotlib, I. H. 2017; 42 (1): 160010-?

  Abstract

  Growing evidence indicates that major depressive disorder (MDD) is characterized by accelerated biological aging, including greater age-related changes in physiological functioning. The disorder is also associated with abnormal neural reward circuitry, particularly in the basal ganglia (BG). Here we assessed age-related changes in BG volume in both patients with MDD and healthy control participants.We obtained whole-brain T1-weighted images from patients with MDD and healthy controls. We estimated grey matter volumes of the BG, including the nucleus accumbens, caudate, pallidum and putamen. Volumes were assessed using multivariate analysis of covariance (MANCOVA) with age as a covariate, followed by appropriate post hoc tests.We included 232 individuals (116 patients with MDD) in our analysis. The MANCOVA yielded a significant group × age interaction (p = 0.043). Analyses for each region yielded a significant group × age interaction in the putamen (univariate test, p = 0.005; permutation test, p = 0.004); this effect was not significant in the other regions. The negative association between age and putamen volume was twice as large in the MDD than in the control group (-35.2 v. -16.7 mm3/yr), indicating greater age-related volumetric decreases in the putamen in individuals with MDD than in controls.These findings are cross-sectional; future studies should assess the longitudinal impact of accelerated aging on anhedonia and neural indices of reward processing.Our results indicate that putamen aging is accelerated in patients with MDD. Thus, the putamen may uniquely contribute to the adverse long-term effects of depressive psychopathology and may be a useful target for the treatment of MDD across the lifespan.

  View details for DOI 10.1503/jpn.160010

  View details for PubMedID 27749245

• Detecting Neuroimaging Biomarkers for Depression: A Meta-analysis of Multivariate Pattern Recognition Studies. Biological psychiatry Kambeitz, J., Cabral, C., Sacchet, M. D., Gotlib, I. H., Zahn, R., Serpa, M. H., Walter, M., Falkai, P., Koutsouleris, N. 2016

  Abstract

  Multiple studies have examined functional and structural brain alteration in patients diagnosed with major depressive disorder (MDD). The introduction of multivariate statistical methods allows investigators to utilize data concerning these brain alterations to generate diagnostic models that accurately differentiate patients with MDD from healthy control subjects (HCs). However, there is substantial heterogeneity in the reported results, the methodological approaches, and the clinical characteristics of participants in these studies.We conducted a meta-analysis of all studies using neuroimaging (volumetric measures derived from T1-weighted images, task-based functional magnetic resonance imaging [MRI], resting-state MRI, or diffusion tensor imaging) in combination with multivariate statistical methods to differentiate patients diagnosed with MDD from HCs.Thirty-three (k = 33) samples including 912 patients with MDD and 894 HCs were included in the meta-analysis. Across all studies, patients with MDD were separated from HCs with 77% sensitivity and 78% specificity. Classification based on resting-state MRI (85% sensitivity, 83% specificity) and on diffusion tensor imaging data (88% sensitivity, 92% specificity) outperformed classifications based on structural MRI (70% sensitivity, 71% specificity) and task-based functional MRI (74% sensitivity, 77% specificity).Our results demonstrate the high representational capacity of multivariate statistical methods to identify neuroimaging-based biomarkers of depression. Future studies are needed to elucidate whether multivariate neuroimaging analysis has the potential to generate clinically useful tools for the differential diagnosis of affective disorders and the prediction of both treatment response and functional outcome.

  View details for DOI 10.1016/j.biopsych.2016.10.028

  View details for PubMedID 28110823

• Large-Scale Hypoconnectivity Between Resting-State Functional Networks in Unmedicated Adolescent Major Depressive Disorder NEUROPSYCHOPHARMACOLOGY Sacchet, M. D., Ho, T. C., Connolly, C. G., Tymofiyeva, O., LeWinn, K. Z., Han, L. K., Blom, E. H., Tapert, S. F., Max, J. E., Frank, G. K., Paulus, M. P., Simmons, A. N., Gotlib, I. H., Yang, T. T. 2016; 41 (12): 2951-2960

  Abstract

  Major depressive disorder (MDD) often emerges during adolescence, a critical period of brain development. Recent resting-state fMRI studies of adults suggest that MDD is associated with abnormalities within and between resting-state networks (RSNs). Here we tested whether adolescent MDD is characterized by abnormalities in interactions among RSNs. Participants were 55 unmedicated adolescents diagnosed with MDD and 56 matched healthy controls. Functional connectivity was mapped using resting-state fMRI. We used the network-based statistic (NBS) to compare large-scale connectivity between groups and also compared the groups on graph metrics. We further assessed whether group differences identified using nodes defined from functionally defined RSNs were also evident when using anatomically defined nodes. In addition, we examined relations between network abnormalities and depression severity and duration. Finally, we compared intranetwork connectivity between groups and assessed the replication of previously reported MDD-related abnormalities in connectivity. The NBS indicated that, compared with controls, depressed adolescents exhibited reduced connectivity (p<0.024, corrected) between a specific set of RSNs, including components of the attention, central executive, salience, and default mode networks. The NBS did not identify group differences in network connectivity when using anatomically defined nodes. Longer duration of depression was significantly correlated with reduced connectivity in this set of network interactions (p=0.020, corrected), specifically with reduced connectivity between components of the dorsal attention network. The dorsal attention network was also characterized by reduced intranetwork connectivity in the MDD group. Finally, we replicated previously reported abnormal connectivity in individuals with MDD. In summary, adolescents with MDD show hypoconnectivity between large-scale brain networks compared with healthy controls. Given that connectivity among these networks typically increases during adolescent neurodevelopment, these results suggest that adolescent depression is associated with abnormalities in neural systems that are still developing during this critical period.

  View details for DOI 10.1038/npp.2016.76

  View details for Web of Science ID 000385212700017

  View details for PubMedID 27238621

  View details for PubMedCentralID PMC5061890

• Attentional bias training in girls at risk for depression. Journal of child psychology and psychiatry, and allied disciplines LeMoult, J., Joormann, J., Kircanski, K., Gotlib, I. H. 2016; 57 (11): 1326-1333

  Abstract

  This study examined, for the first time, whether attentional biases can be modified in adolescents at risk for depression.The final sample consisted of 41 girls at familial risk for depression, who were randomly assigned to receive six sessions (864 trials) of real or sham attention bias training [Real attentional bias training (ABT) vs. Sham ABT]. Participants who received Real ABT completed a modified dot-probe task designed to train attention toward positive and away from negative facial expressions; in contrast, girls who received Sham ABT completed the standard dot-probe task. Attentional biases, self-reported mood, and psychophysiological responses to stress were measured at pre- and post-training assessments.As expected, girls who received Real ABT, but not those who received Sham ABT, exhibited significant increases from pre- to post-training in their attention toward happy faces and away from sad faces. Moreover, adolescents who received Real ABT were buffered against the negative outcomes experienced by adolescents who received Sham ABT. Specifically, only adolescents who received Sham ABT experienced an increase in negative mood and a pre- to post-training increase in heart rate in anticipation of the stressor.The current findings provide the first experimental evidence that attentional biases can be modified in youth at risk for depression and further suggest that ABT modulates the heightened response to stress that is otherwise experienced by high-risk adolescents.

  View details for DOI 10.1111/jcpp.12587

  View details for PubMedID 27390111

  View details for PubMedCentralID PMC5093061

• The application of neuroimaging to social inequity and language disparity: A cautionary examination. Developmental cognitive neuroscience Ellwood-Lowe, M. E., Sacchet, M. D., Gotlib, I. H. 2016; 22: 1-8

  Abstract

  In the nascent field of the cognitive neuroscience of socioeconomic status (SES), researchers are using neuroimaging to examine how growing up in poverty affects children's neurocognitive development, particularly their language abilities. In this review we highlight difficulties inherent in the frequent use of reverse inference to interpret SES-related abnormalities in brain regions that support language. While there is growing evidence suggesting that SES moderates children's developing brain structure and function, no studies to date have elucidated explicitly how these neural findings are related to variations in children's language abilities, or precisely what it is about SES that underlies or contributes to these differences. This issue is complicated by the fact that SES is confounded with such linguistic factors as cultural language use, first language, and bilingualism. Thus, SES-associated differences in brain regions that support language may not necessarily indicate differences in neurocognitive abilities. In this review we consider the multidimensionality of SES, discuss studies that have found SES-related differences in structure and function in brain regions that support language, and suggest future directions for studies in the area of cognitive neuroscience of SES that are less reliant on reverse inference.

  View details for DOI 10.1016/j.dcn.2016.10.001

  View details for PubMedID 27744097

  View details for PubMedCentralID PMC5135574

• The grass is not as green as you think: Affect evaluation in people with internalizing disorders. Journal of affective disorders Thompson, R. J., Kircanski, K., Gotlib, I. H. 2016; 203: 233-240

  Abstract

  Affect evaluation - how people evaluate their emotion experiences - has important implications for mental health.We examined how 70 adults diagnosed with Major Depressive Disorder and/or Generalized Anxiety Disorder or no psychiatric disorders (control group) believe they should feel in the moment (should affect). We repeatedly assessed participants' current affect and should affect over one week using experience sampling. To examine the psychometric properties of should affect, participants rated their level of rumination at each survey and completed trait measures of brooding and ideal affect at the lab.Independent of group status, participants reported that they should be feeling more positive affect and less negative affect. Even after accounting for mean affect, the clinical groups' reports were generally more extreme than were those of the control group. We documented good convergent and discriminant validity of should affect. Finally, we describe clinical implications and directions for future research.

  View details for DOI 10.1016/j.jad.2016.06.006

  View details for PubMedID 27295379

  View details for PubMedCentralID PMC4975967

• EARLY MARKERS OF STRESS IN HIGH-RISK OFFSPRING Singh, M. K., Bhattacharjee, K., Soudi, L., Ghosh, P., Foland-Ross, L., Gotlib, I., Chang, K. D. ELSEVIER SCIENCE INC. 2016: S300

  View details for DOI 10.1016/j.jaac.2016.07.274

  View details for Web of Science ID 000541964302097

• NEURAL AND BEHAVIORAL CHARACTERISTICS OF RISK AND RESILIENCE IN YOUTH OFFSPRING OF PARENTS WITH BIPOLAR DISORDER Singh, M. K., Chang, K. D., Bhattacharjee, K., Rossallini, B., Kelley, R., Kim, E., Gotlib, I. ELSEVIER SCIENCE INC. 2016: S285

  View details for DOI 10.1016/j.jaac.2016.07.220

  View details for Web of Science ID 000541964302051

• Intergenerational Neuroimaging of Human Brain Circuitry TRENDS IN NEUROSCIENCES Ho, T. C., Sanders, S. J., Gotlib, I. H., Hoeft, F. 2016; 39 (10): 644–48

  Abstract

  Neuroscientists are increasingly using advanced neuroimaging methods to elucidate the intergenerational transmission of human brain circuitry. This new line of work promises to shed light on the ontogeny of complex behavioral traits, including psychiatric disorders, and possible mechanisms of transmission. Here we highlight recent intergenerational neuroimaging studies and provide recommendations for future work.

  View details for PubMedID 27623194

• The serotonin transporter promoter variant, stress, and attentional biases in middle childhood PERSONALITY AND INDIVIDUAL DIFFERENCES Kotelnikova, Y., LeMoult, J., Mackrell, S. V., Sheikh, H. I., Singh, S. M., Joormann, J., Gotlib, I. H., Hayden, E. P. 2016; 101: 371-379

  Abstract

  Although evidence suggests that 5-HTTLPR variants may shape risk for depression, the influence is likely complex, and involves effects on endophenotypes. We examined associations between 5-HTTLPR and biases in attention to affective stimuli in a sample of girls and a sample of both boys and girls. Children with at least one short (S) variant of the 5-HTTLPR polymorphism had lower positive attentional bias scores in both samples. This association was qualified by an interaction with stress in one sample, such that links between the S allele and decreased positive attentional bias was significant only when life stress was elevated. This difference in findings between the two samples was explained by sex differences in samples; the GXE interaction was significant only in boys. Findings are discussed in the context of sex differences in GXE.

  View details for DOI 10.1016/j.paid.2016.06.004

  View details for Web of Science ID 000383003300060

  View details for PubMedCentralID PMC5147753

• Attentional avoidance of fearful facial expressions following early life stress is associated with impaired social functioning. Journal of child psychology and psychiatry, and allied disciplines Humphreys, K. L., Kircanski, K., Colich, N. L., Gotlib, I. H. 2016; 57 (10): 1174-1182

  Abstract

  Early life stress is associated with poorer social functioning. Attentional biases in response to threat-related cues, linked to both early experience and psychopathology, may explain this association. To date, however, no study has examined attentional biases to fearful facial expressions as a function of early life stress or examined these biases as a potential mediator of the relation between early life stress and social problems.In a sample of 154 children (ages 9-13 years) we examined the associations among interpersonal early life stressors (i.e., birth through age 6 years), attentional biases to emotional facial expressions using a dot-probe task, and social functioning on the Child Behavior Checklist.High levels of early life stress were associated with both greater levels of social problems and an attentional bias away from fearful facial expressions, even after accounting for stressors occurring in later childhood. No biases were found for happy or sad facial expressions as a function of early life stress. Finally, attentional biases to fearful faces mediated the association between early life stress and social problems.Attentional avoidance of fearful facial expressions, evidenced by a bias away from these stimuli, may be a developmental response to early adversity and link the experience of early life stress to poorer social functioning.

  View details for DOI 10.1111/jcpp.12607

  View details for PubMedID 27457566

  View details for PubMedCentralID PMC5030156

• Cognitive and neural consequences of memory suppression in major depressive disorder. Cognitive, affective & behavioral neuroscience Sacchet, M. D., Levy, B. J., Hamilton, J. P., Maksimovskiy, A., Hertel, P. T., Joormann, J., Anderson, M. C., Wagner, A. D., Gotlib, I. H. 2016: -?

  Abstract

  Negative biases in cognition have been documented consistently in major depressive disorder (MDD), including difficulties in the ability to control the processing of negative material. Although negative information-processing biases have been studied using both behavioral and neuroimaging paradigms, relatively little research has been conducted examining the difficulties of depressed persons with inhibiting the retrieval of negative information from long-term memory. In this study, we used the think/no-think paradigm and functional magnetic resonance imaging to assess the cognitive and neural consequences of memory suppression in individuals diagnosed with depression and in healthy controls. The participants showed typical behavioral forgetting effects, but contrary to our hypotheses, there were no differences between the depressed and nondepressed participants or between neutral and negative memories. Relative to controls, depressed individuals exhibited greater activity in right middle frontal gyrus during memory suppression, regardless of the valence of the suppressed stimuli, and differential activity in the amygdala and hippocampus during memory suppression involving negatively valenced stimuli. These findings indicate that depressed individuals are characterized by neural anomalies during the suppression of long-term memories, increasing our understanding of the brain bases of negative cognitive biases in MDD.

  View details for PubMedID 27649971

• Ruminative brooding is associated with salience network coherence in early pubertal youth. Social cognitive and affective neuroscience Ordaz, S. J., LeMoult, J., Colich, N. L., Prasad, G., Pollak, M., Popolizio, M., Price, A., Greicius, M., Gotlib, I. H. 2016

  Abstract

  Rumination, and particularly ruminative brooding, perpetuates dysphoric mood states and contributes to the emergence of depression. Studies of adults and older adolescents have characterized the association between rumination and intrinsic functional connectivity within default mode (DMN), salience (SN) and executive control (ECN) networks; we know little, however, about the brain network basis of rumination during early puberty, a sensitive period for network reorganization. 112 early puberty boys and girls completed resting-state scans, the Ruminative Response Scale, and the Youth Self-Report questionnaire. Using independent components analysis and dual regression, we quantified coherence for each individual in networks of interest (SN, ECN, DMN) and in non-relevant networks (motor, visual) in which we predicted no correlations with behavioral measures. Boys and girls did not differ in levels of rumination or internalizing symptoms, or in coherence for any network. The relation between SN network coherence and rumination; however, and specifically ruminative brooding, was moderated by sex: greater SN coherence was associated with higher levels of brooding in girls but not in boys. Further, in girls, brooding mediated the relation between SN coherence and internalizing symptoms. These results point to coherence within the SN as a potential neurodevelopmental marker of risk for depression in early pubertal girls.

  View details for DOI 10.1093/scan/nsw133

  View details for PubMedID 27633394

  View details for PubMedCentralID PMC5390708

• Neurofeedback training for major depressive disorder: recent developments and future directions. Expert review of neurotherapeutics Sacchet, M. D., Gotlib, I. H. 2016; 16 (9): 1003-1005

  View details for DOI 10.1080/14737175.2016.1199959

  View details for PubMedID 27310296

  View details for PubMedCentralID PMC5018155

• The Serotonin Transporter Promoter Variant, Stress, and Attentional Biases in Middle Childhood. Personality and individual differences Kotelnikova, Y., LeMoult, J., Mackrell, S. V., Sheikh, H. I., Singh, S. M., Joormann, J., Gotlib, I. H., Hayden, E. P. 2016; 101: 371-379

  Abstract

  Although evidence suggests that 5-HTTLPR variants may shape risk for depression, the influence is likely complex, and involves effects on endophenotypes. We examined associations between 5-HTTLPR and biases in attention to affective stimuli in a sample of girls and a sample of both boys and girls. Children with at least one short (S) variant of the 5-HTTLPR polymorphism had lower positive attentional bias scores in both samples. This association was qualified by an interaction with stress in one sample, such that links between the S allele and decreased positive attentional bias was significant only when life stress was elevated. This difference in findings between the two samples was explained by sex differences in samples; the GXE interaction was significant only in boys. Findings are discussed in the context of sex differences in GXE.

  View details for DOI 10.1016/j.paid.2016.06.004

  View details for PubMedID 27956753

  View details for PubMedCentralID PMC5147753

• Investigating the nature of co-occurring depression and anxiety: Comparing diagnostic and dimensional research approaches. Journal of affective disorders Kircanski, K., LeMoult, J., Ordaz, S., Gotlib, I. H. 2016

  Abstract

  Although approximately half of adults diagnosed with a depressive or anxiety disorder exhibit their simultaneous co-occurrence, traditional research has centered on single-target diagnoses, overlooking comorbidities within samples. In this article, we review and extend the literature that directly investigates co-occurring depression and anxiety, with the goal of shifting the focus from co-occurring diagnoses to symptom dimensions.First, we review studies that have directly compared psychobiological features (neural, neuroendocrine, autonomic) across depression, anxiety, and their co-occurrence, defined either categorically or dimensionally. Second, we analyze adults' diurnal cortisol secretion to examine the independent and interactive relations of continuously-assessed depressive and anxiety symptoms to neuroendocrine function.Previous findings on the psychobiology of diagnostic co-occurrence are mixed. While nascent, evidence from dimensionally focused studies suggests that co-occurring levels of depressive and anxiety symptoms can interact with one another, as reflected in a distinct psychobiological profile for individuals with high levels of both symptom dimensions. Results of our analyses support this formulation: we found that depressive and anxiety symptom dimensions interacted consistently in their relation to the measures of diurnal cortisol.The illustrative sample was relatively small and included only women; future research should examine generalizability of these findings.A dimensional approach to investigating the psychobiology of co-occurring depression and anxiety affords both conceptual and practical advantages. Simultaneously assessing depressive and anxiety symptom dimensions can efficiently capture their unique, shared, and interactive features, thereby identifying targets for intervention across a wide range of symptom presentations.

  View details for DOI 10.1016/j.jad.2016.08.006

  View details for PubMedID 27554605

• Revisiting Depression Contagion as a Mediator of the Relation Between Depression and Rejection: A Speed-Dating Study. Clinical psychological science : a journal of the Association for Psychological Science Pe, M. L., Gotlib, I. H., Van Den Noortgate, W., Kuppens, P. 2016; 4 (4): 675-682

  Abstract

  Interpersonal theories of depression postulate that depressed individuals' experience of social isolation is attributable, in part, to their tendency to behave in ways that elicit rejection from others. Depression contagion has been implicated as a factor that may account for the rejection of depressed individuals. The current study revisits this hypothesis using a controlled, but realistically motivated setting: speed-dating. Approximately two weeks before the speed-dating event, participants' depression levels were assessed. During the event, participants had four-minute "dates" with opposite-sex partners. After each date, they responded to items measuring their affect and romantic attraction. At the end of the evening, participants indicated which partners they wanted to see again. Our results did not support depression contagion: after four minutes of interaction with partners with high levels of depressive symptoms, participants did not experience increased negative affect; instead, they experienced reduced positive affect, which led to the rejection of these partners.

  View details for PubMedID 27595052

• Common Measures for National Institute of Mental Health Funded Research BIOLOGICAL PSYCHIATRY Barch, D. M., Gotlib, I. H., Bilder, R. M., Pine, D. S., Smoller, J. W., Brown, C., Huggins, W., Hamilton, C., Haim, A., Farber, G. K. 2016; 79 (12): E91–E96

  View details for PubMedID 26903402

  View details for PubMedCentralID PMC4968690

• Common and distinct patterns of grey-matter volume alteration in major depression and bipolar disorder: evidence from voxel-based meta-analysis. Molecular psychiatry Wise, T., Radua, J., VIA, E., Cardoner, N., Abe, O., Adams, T. M., Amico, F., Cheng, Y., Cole, J. H., de Azevedo Marques Périco, C., Dickstein, D. P., Farrow, T. F., Frodl, T., Wagner, G., Gotlib, I. H., Gruber, O., Ham, B. J., Job, D. E., Kempton, M. J., Kim, M. J., Koolschijn, P. C., Malhi, G. S., Mataix-Cols, D., McIntosh, A. M., Nugent, A. C., O'Brien, J. T., Pezzoli, S., Phillips, M. L., Sachdev, P. S., Salvadore, G., Selvaraj, S., Stanfield, A. C., Thomas, A. J., van Tol, M. J., van der Wee, N. J., Veltman, D. J., Young, A. H., Fu, C. H., Cleare, A. J., Arnone, D. 2016

  Abstract

  Finding robust brain substrates of mood disorders is an important target for research. The degree to which major depression (MDD) and bipolar disorder (BD) are associated with common and/or distinct patterns of volumetric changes is nevertheless unclear. Furthermore, the extant literature is heterogeneous with respect to the nature of these changes. We report a meta-analysis of voxel-based morphometry (VBM) studies in MDD and BD. We identified studies published up to January 2015 that compared grey matter in MDD (50 data sets including 4101 individuals) and BD (36 data sets including 2407 individuals) using whole-brain VBM. We used statistical maps from the studies included where available and reported peak coordinates otherwise. Group comparisons and conjunction analyses identified regions in which the disorders showed common and distinct patterns of volumetric alteration. Both disorders were associated with lower grey-matter volume relative to healthy individuals in a number of areas. Conjunction analysis showed smaller volumes in both disorders in clusters in the dorsomedial and ventromedial prefrontal cortex, including the anterior cingulate cortex and bilateral insula. Group comparisons indicated that findings of smaller grey-matter volumes relative to controls in the right dorsolateral prefrontal cortex and left hippocampus, along with cerebellar, temporal and parietal regions were more substantial in major depression. These results suggest that MDD and BD are characterised by both common and distinct patterns of grey-matter volume changes. This combination of differences and similarities has the potential to inform the development of diagnostic biomarkers for these conditions.Molecular Psychiatry advance online publication, 24 May 2016; doi:10.1038/mp.2016.72.

  View details for DOI 10.1038/mp.2016.72

  View details for PubMedID 27217146

• Cortical abnormalities in adults and adolescents with major depression based on brain scans from 20 cohorts worldwide in the ENIGMA Major Depressive Disorder Working Group. Molecular psychiatry Schmaal, L., Hibar, D. P., Sämann, P. G., Hall, G. B., Baune, B. T., Jahanshad, N., Cheung, J. W., van Erp, T. G., Bos, D., Ikram, M. A., Vernooij, M. W., Niessen, W. J., Tiemeier, H., Hofman, A., Wittfeld, K., Grabe, H. J., Janowitz, D., Bülow, R., Selonke, M., Völzke, H., Grotegerd, D., Dannlowski, U., Arolt, V., Opel, N., Heindel, W., Kugel, H., Hoehn, D., Czisch, M., Couvy-Duchesne, B., Rentería, M. E., Strike, L. T., Wright, M. J., MILLS, N. T., de Zubicaray, G. I., McMahon, K. L., Medland, S. E., Martin, N. G., Gillespie, N. A., Goya-Maldonado, R., Gruber, O., Krämer, B., Hatton, S. N., Lagopoulos, J., Hickie, I. B., Frodl, T., Carballedo, A., Frey, E. M., Van Velzen, L. S., Penninx, B. W., van Tol, M., Van der Wee, N. J., DAVEY, C. G., Harrison, B. J., Mwangi, B., Cao, B., Soares, J. C., Veer, I. M., Walter, H., Schoepf, D., Zurowski, B., Konrad, C., Schramm, E., Normann, C., Schnell, K., Sacchet, M. D., Gotlib, I. H., MacQueen, G. M., Godlewska, B. R., Nickson, T., McIntosh, A. M., Papmeyer, M., Whalley, H. C., Hall, J., Sussmann, J. E., Li, M., Walter, M., Aftanas, L., Brack, I., Bokhan, N. A., Thompson, P. M., Veltman, D. J. 2016

  Abstract

  The neuro-anatomical substrates of major depressive disorder (MDD) are still not well understood, despite many neuroimaging studies over the past few decades. Here we present the largest ever worldwide study by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Major Depressive Disorder Working Group on cortical structural alterations in MDD. Structural T1-weighted brain magnetic resonance imaging (MRI) scans from 2148 MDD patients and 7957 healthy controls were analysed with harmonized protocols at 20 sites around the world. To detect consistent effects of MDD and its modulators on cortical thickness and surface area estimates derived from MRI, statistical effects from sites were meta-analysed separately for adults and adolescents. Adults with MDD had thinner cortical gray matter than controls in the orbitofrontal cortex (OFC), anterior and posterior cingulate, insula and temporal lobes (Cohen's d effect sizes: -0.10 to -0.14). These effects were most pronounced in first episode and adult-onset patients (>21 years). Compared to matched controls, adolescents with MDD had lower total surface area (but no differences in cortical thickness) and regional reductions in frontal regions (medial OFC and superior frontal gyrus) and primary and higher-order visual, somatosensory and motor areas (d: -0.26 to -0.57). The strongest effects were found in recurrent adolescent patients. This highly powered global effort to identify consistent brain abnormalities showed widespread cortical alterations in MDD patients as compared to controls and suggests that MDD may impact brain structure in a highly dynamic way, with different patterns of alterations at different stages of life.Molecular Psychiatry advance online publication, 3 May 2016; doi:10.1038/mp.2016.60.

  View details for DOI 10.1038/mp.2016.60

  View details for PubMedID 27137745

• Habenula responses to potential and actual loss in major depression: preliminary evidence for lateralized dysfunction SOCIAL COGNITIVE AND AFFECTIVE NEUROSCIENCE Furman, D. J., Gotlib, I. H. 2016; 11 (5): 843-851

  Abstract

  The habenula has been implicated in predicting negative events and in responding to unexpected negative outcomes. Animal models of depression have supported the hypothesis that perturbations in habenula activity contribute to the pathophysiology of Major Depressive Disorder (MDD), a psychiatric illness characterized by abnormalities in responding to negative feedback and by pessimism in evaluating the likelihood of future events. No research to date, however, has examined human habenula responses to potential and experienced negative outcomes in MDD. In this study, depressed and healthy control participants performed a probabilistic guessing task for monetary rewards and penalties during high-resolution functional magnetic resonance imaging of the habenula. In healthy adults, we observed a pattern of habenula activation consistent with its hypothesized role in predicting future losses and responding to suboptimal outcomes. In contrast, in depressed participants the left habenula was not activated significantly during the prediction or experience of monetary penalty. Complementing this group difference, attenuated habenula activation to negative feedback in control participants was associated with levels of shame and rumination. The results of this study suggest that depressed individuals are characterized by dysfunction in a neural system involved in generating expectations and comparing expectations with objective outcomes.

  View details for DOI 10.1093/scan/nsw019

  View details for Web of Science ID 000376655100016

  View details for PubMedID 26884545

  View details for PubMedCentralID PMC4847703

• Task-positive and Task-negative Functional Networks in Adolescent Depression Ho, T. C., Sacchet, M. D., Margulies, D. S., Connolly, C. G., Simmons, A. N., Gotlib, I. H., Yang, T. ELSEVIER SCIENCE INC. 2016: 22S

  View details for Web of Science ID 000432440800056

• Longitudinal Changes in Striatal Response to the Anticipation of Reward Correlates with Changes in Depressive Symptomatology in Adolescent Females Colich, N. L., Pollak, M., Ordaz, S. J., Gotlib, I. H. ELSEVIER SCIENCE INC. 2016: 193S

  View details for Web of Science ID 000432440802137

• Neural Mechanisms Underlying the Generation of Negative Affect in Major Depressive Disorder Davis, E., Foland-Ross, L. C., Colich, N. L., Gotlib, I. H. ELSEVIER SCIENCE INC. 2016: 193S

  View details for Web of Science ID 000432440802138

• Accelerated Aging of the Putamen in Major Depressive Disorder Camacho, M. C., Sacchet, M. D., Livermore, E. E., Gotlib, I. H., Thomas, E. ELSEVIER SCIENCE INC. 2016: 244S–245S

  View details for Web of Science ID 000432440803102

• Evidence for a Sensitive Period in the Effects of Early Life Stress on Human Hippocampal Volume Humphreys, K. L., Sacchet, M. D., Camacho, M. C., King, L. S., Ordaz, S. J., Colich, N. L., Gotlib, I. H. ELSEVIER SCIENCE INC. 2016: 19S

  View details for Web of Science ID 000432440800049

• Hypoconnectivity among Resting-state Functional Networks in Adolescent Major Depression Sacchet, M. D., Ho, T. C., Connolly, C. G., Tymofiyeva, O., Lewinn, K. Z., Han, L. M., Blom, E., Tapert, S. F., Max, J. E., Frank, G. W., Paulus, M. P., Simmons, A. N., Gotlib, I. H., Yang, T. Y. ELSEVIER SCIENCE INC. 2016: 245S

  View details for Web of Science ID 000432440803103

• Sex-Specific Pathways to Delinquency in Early Adolescence: The Effects of Stress and Gonadal Hormones Popolizio, M. M., Humphreys, K. L., Colich, N. L., Gotlib, I. H. ELSEVIER SCIENCE INC. 2016: 414S–415S

  View details for Web of Science ID 000432440805165

• Biological Stress Reactivity as a Risk Factor for Internalizing Disorders in Early-Pubertal Children: The Moderating Effects of Stress Exposure Gotlib, I. H., Colich, N. L., LeMoult, J., Kircanski, K., Humphreys, K. L. ELSEVIER SCIENCE INC. 2016: 180S

  View details for Web of Science ID 000432440802105

• The Impact of Early Life Stress on Diurnal Cortisol Regulation: The Role of Puberty King, L. S., Colich, N. L., Lemoult, J., Gotlib, I. H. ELSEVIER SCIENCE INC. 2016: 372S–373S

  View details for Web of Science ID 000432440805062

• Ruminative Brooding Mediates the Relation Between Salience Network Coherence and Internalizing Symptoms in Early Adolescent Females Ordaz, S., LeMoult, J., Colich, N., Prasad, G., Greicius, M., Gotlib, I. ELSEVIER SCIENCE INC. 2016: 301S

  View details for Web of Science ID 000432440804053

• Computational meta-analysis of statistical parametric maps in major depression HUMAN BRAIN MAPPING Arnone, D., Job, D., Selvaraj, S., Abe, O., Amico, F., Cheng, Y., Colloby, S. J., O'Brien, J. T., Frodl, T., Gotlib, I. H., Ham, B., Kim, M. J., Koolschijn, P. C., Perico, C. A., Salvadore, G., Thomas, A. J., van Tol, M., van der Wee, N. J., Veltman, D. J., Wagner, G., McIntosh, A. M. 2016; 37 (4): 1393-1404

  Abstract

  Several neuroimaging meta-analyses have summarized structural brain changes in major depression using coordinate-based methods. These methods might be biased toward brain regions where significant differences were found in the original studies. In this study, a novel voxel-based technique is implemented that estimates and meta-analyses between-group differences in grey matter from individual MRI studies, which are then applied to the study of major depression.A systematic review and meta-analysis of voxel-based morphometry studies were conducted comparing participants with major depression and healthy controls by using statistical parametric maps. Summary effect sizes were computed correcting for multiple comparisons at the voxel level. Publication bias and heterogeneity were also estimated and the excess of heterogeneity was investigated with metaregression analyses.Patients with major depression were characterized by diffuse bilateral grey matter loss in ventrolateral and ventromedial frontal systems extending into temporal gyri compared to healthy controls. Grey matter reduction was also detected in the right parahippocampal and fusiform gyri, hippocampus, and bilateral thalamus. Other areas included parietal lobes and cerebellum. There was no evidence of statistically significant publication bias or heterogeneity.The novel computational meta-analytic approach used in this study identified extensive grey matter loss in key brain regions implicated in emotion generation and regulation. Results are not biased toward the findings of the original studies because they include all available imaging data, irrespective of statistically significant regions, resulting in enhanced detection of additional areas of grey matter loss. Hum Brain Mapp 37:1393-1404, 2016. © 2016 Wiley Periodicals, Inc.

  View details for DOI 10.1002/hbm.23108

  View details for PubMedID 26854015

• Revising the BIS/BAS Scale to study development: Measurement invariance and normative effects of age and sex from childhood through adulthood. Psychological assessment Pagliaccio, D., Luking, K. R., Anokhin, A. P., Gotlib, I. H., Hayden, E. P., Olino, T. M., Peng, C., Hajcak, G., Barch, D. M. 2016; 28 (4): 429-442

  Abstract

  Carver and White's (1994) Behavioral Inhibition System/Behavioral Activation System (BIS/BAS) Scales have been useful tools for studying individual differences in reward-punishment sensitivity; however, their factor structure and invariance across development have not been well tested. In the current study, we examined the factor structure of the BIS/BAS Scales across 5 age groups: 6- to 10-year-old children (N = 229), 11- to 13-year-old early adolescents (N = 311), 14- to 16-year-old late adolescents (N = 353), 18- to 22-year-old young adults (N = 844), and 30- to 45-year-old adults (N = 471). Given poor fit of the standard 4-factor model (BIS, Reward Responsivity, Drive, Fun Seeking) in the literature, we conducted exploratory factor analyses in half of the participants and identified problematic items across age groups. The 4-factor model showed poor fit in our sample, whereas removing the BAS Fun Seeking subscale and problematic items from the remaining subscales improved fit in confirmatory factor analyses conducted with the second half of the participants. The revised model showed strict invariance across age groups and by sex, indicating consistent factor structure, item loadings, thresholds, and unique or residual variances. Additionally, in our cross-sectional data, we observed nonlinear relations between age and subscale scores, where scores tended to be higher in young adulthood than in childhood and later adulthood. Furthermore, sex differences emerged across development; adolescent and adult females had higher BIS scores than males in this age range, whereas sex differences were not observed in childhood. These differences may help us to understand the rise in internalizing psychopathology in adolescence, particularly in females. Future developmental studies are warranted to examine the impact of rewording problematic items. (PsycINFO Database Record

  View details for DOI 10.1037/pas0000186

  View details for PubMedID 26302106

• Attentional bias in euthymic bipolar I disorder. Cognition & emotion Peckham, A. D., Johnson, S. L., Gotlib, I. H. 2016; 30 (3): 472-487

  Abstract

  Little is known about the nature of the relation between information-processing biases and affective traits in bipolar disorder. The present study was designed to investigate whether attentional biases are evident in persons diagnosed with bipolar disorder when they are in a positive mood state, and whether biases are related to indices of emotion regulation and to prior history of mood episodes. Ninety adults diagnosed with bipolar I disorder and 81 controls with no lifetime mood disorder underwent a positive mood induction and then completed an emotion face dot-probe task; participants in the bipolar disorder group also completed a self-report measure of responses to positive affect. Attentional bias was not related to a diagnosis of bipolar disorder or to symptom severity. Consistent with hypotheses, analyses within the bipolar group indicated that greater dampening of positive affect related to significantly less attention paid to the positively valenced faces. Discussion focuses on the potential role of affective traits in shaping attentional bias in bipolar disorder.

  View details for DOI 10.1080/02699931.2015.1014313

  View details for PubMedID 25757517

  View details for PubMedCentralID PMC4567549

• Revising the BIS/BAS Scale to Study Development: Measurement Invariance and Normative Effects of Age and Sex From Childhood Through Adulthood PSYCHOLOGICAL ASSESSMENT Pagliaccio, D., Luking, K. R., Anokhin, A. P., Gotlib, I. H., Hayden, E. P., Olino, T. M., Peng, C., Hajcak, G., Barch, D. M. 2016; 28 (4): 429-442

  Abstract

  Carver and White's (1994) Behavioral Inhibition System/Behavioral Activation System (BIS/BAS) Scales have been useful tools for studying individual differences in reward-punishment sensitivity; however, their factor structure and invariance across development have not been well tested. In the current study, we examined the factor structure of the BIS/BAS Scales across 5 age groups: 6- to 10-year-old children (N = 229), 11- to 13-year-old early adolescents (N = 311), 14- to 16-year-old late adolescents (N = 353), 18- to 22-year-old young adults (N = 844), and 30- to 45-year-old adults (N = 471). Given poor fit of the standard 4-factor model (BIS, Reward Responsivity, Drive, Fun Seeking) in the literature, we conducted exploratory factor analyses in half of the participants and identified problematic items across age groups. The 4-factor model showed poor fit in our sample, whereas removing the BAS Fun Seeking subscale and problematic items from the remaining subscales improved fit in confirmatory factor analyses conducted with the second half of the participants. The revised model showed strict invariance across age groups and by sex, indicating consistent factor structure, item loadings, thresholds, and unique or residual variances. Additionally, in our cross-sectional data, we observed nonlinear relations between age and subscale scores, where scores tended to be higher in young adulthood than in childhood and later adulthood. Furthermore, sex differences emerged across development; adolescent and adult females had higher BIS scores than males in this age range, whereas sex differences were not observed in childhood. These differences may help us to understand the rise in internalizing psychopathology in adolescence, particularly in females. Future developmental studies are warranted to examine the impact of rewording problematic items. (PsycINFO Database Record

  View details for DOI 10.1037/pas0000186

  View details for Web of Science ID 000372968600010

  View details for PubMedCentralID PMC4766059

• Effects of salience-network-node neurofeedback training on affective biases in major depressive disorder PSYCHIATRY RESEARCH-NEUROIMAGING Hamilton, J. P., Glover, G. H., Bagarinao, E., Chang, C., Mackey, S., Sacchet, M. D., Gotlib, I. H. 2016; 249: 91-96

  Abstract

  Neural models of major depressive disorder (MDD) posit that over-response of components of the brain's salience network (SN) to negative stimuli plays a crucial role in the pathophysiology of MDD. In the present proof-of-concept study, we tested this formulation directly by examining the affective consequences of training depressed persons to down-regulate response of SN nodes to negative material. Ten participants in the real neurofeedback group saw, and attempted to learn to down-regulate, activity from an empirically identified node of the SN. Ten other participants engaged in an equivalent procedure with the exception that they saw SN-node neurofeedback indices from participants in the real neurofeedback group. Before and after scanning, all participants completed tasks assessing emotional responses to negative scenes and to negative and positive self-descriptive adjectives. Compared to participants in the sham-neurofeedback group, from pre- to post-training, participants in the real-neurofeedback group showed a greater decrease in SN-node response to negative stimuli, a greater decrease in self-reported emotional response to negative scenes, and a greater decrease in self-reported emotional response to negative self-descriptive adjectives. Our findings provide support for a neural formulation in which the SN plays a primary role in contributing to negative cognitive biases in MDD.

  View details for DOI 10.1016/j.pscychresns.2016.01.016

  View details for Web of Science ID 000372526600012

  View details for PubMedCentralID PMC4803612

• Effects of salience-network-node neurofeedback training on affective biases in major depressive disorder. Psychiatry research Hamilton, J. P., Glover, G. H., Bagarinao, E., Chang, C., Mackey, S., Sacchet, M. D., Gotlib, I. H. 2016; 249: 91-96

  Abstract

  Neural models of major depressive disorder (MDD) posit that over-response of components of the brain's salience network (SN) to negative stimuli plays a crucial role in the pathophysiology of MDD. In the present proof-of-concept study, we tested this formulation directly by examining the affective consequences of training depressed persons to down-regulate response of SN nodes to negative material. Ten participants in the real neurofeedback group saw, and attempted to learn to down-regulate, activity from an empirically identified node of the SN. Ten other participants engaged in an equivalent procedure with the exception that they saw SN-node neurofeedback indices from participants in the real neurofeedback group. Before and after scanning, all participants completed tasks assessing emotional responses to negative scenes and to negative and positive self-descriptive adjectives. Compared to participants in the sham-neurofeedback group, from pre- to post-training, participants in the real-neurofeedback group showed a greater decrease in SN-node response to negative stimuli, a greater decrease in self-reported emotional response to negative scenes, and a greater decrease in self-reported emotional response to negative self-descriptive adjectives. Our findings provide support for a neural formulation in which the SN plays a primary role in contributing to negative cognitive biases in MDD.

  View details for DOI 10.1016/j.pscychresns.2016.01.016

  View details for PubMedID 26862057

  View details for PubMedCentralID PMC4803612

• Impaired Retrieval Inhibition of Threat Material in Generalized Anxiety Disorder. Clinical psychological science : a journal of the Association for Psychological Science Kircanski, K., Johnson, D. C., Mateen, M., Bjork, R. A., Gotlib, I. H. 2016; 4 (2): 320-327

  Abstract

  Generalized Anxiety Disorder (GAD) is characterized by cognitive biases toward threat-relevant information, but the underlying mechanisms are unclear. We translated a retrieval-practice paradigm from cognitive science to investigate impaired inhibition of threat information as one such mechanism. Participants diagnosed with GAD and never-disordered control participants learned a series of cue-target pairs; whereas some cues were associated only with neutral targets, others were associated with both neutral and threat targets. Next, participants practiced retrieving neutral targets, which typically suppresses the subsequent recall of unpracticed associated targets (retrieval-induced forgetting; RIF). Finally, participants were tested on their recall of all targets. Despite showing intact RIF of neutral targets, the GAD group failed to exhibit RIF of threat targets. Furthermore, within the GAD group, less RIF of threat targets correlated with greater pervasiveness of worry. Deficits in inhibitory control over threat-relevant information may underlie the cognitive pathology of GAD, which has important treatment implications.

  View details for PubMedID 27042388

• Aberrant Parasympathetic Stress Responsivity in Pure and Co-Occurring Major Depressive Disorder and Generalized Anxiety Disorder JOURNAL OF PSYCHOPATHOLOGY AND BEHAVIORAL ASSESSMENT Kircanski, K., Waugh, C. E., Camacho, M. C., Gotlib, I. H. 2016; 38 (1): 5-19

  View details for DOI 10.1007/s10862-015-9493-y

  View details for Web of Science ID 000372328300002

• Affective Updating Ability and Stressful Events Interact to Prospectively Predict Increases in Depressive Symptoms Over Time EMOTION Pe, M. L., Brose, A., Gotlib, I. H., Kuppens, P. 2016; 16 (1): 73-82

  Abstract

  Previous research has emphasized the critical role of negative cognitions as a vulnerability factor in predicting depressive symptoms. Here, the authors argue that processes that function to maintain negative cognitions may serve as a catalyst for the development of depressive symptoms in the context of negative circumstances, and they suggest that poor updating of affective information in working memory is 1 such process. Thus, they posit that under high levels of stress, individuals with poor affective updating are hindered in changing the negative content in working memory associated with stressful events and, therefore, are more likely to experience increased depressive symptoms over time. To examine this hypothesis, the authors assessed affective updating ability, stress, and depressive symptoms in 200 students who were entering their first year of tertiary education. They assessed levels of depressive symptoms again both 4 months and 1 year later. Under high levels of stress, poor affective updating ability was associated with an increase in depressive symptoms at both 4 months and 1 year later. These results demonstrate that affective updating ability is an important cognitive vulnerability factor that interacts with stressful events to accelerate the development of depressive symptoms, and underscore the importance of designing early prevention or intervention approaches for individuals with this cognitive vulnerability.

  View details for DOI 10.1037/emo0000097

  View details for Web of Science ID 000370183800011

  View details for PubMedID 26322571

  View details for PubMedCentralID PMC4718857

• Neural Aspects of Inhibition Following Emotional Primes in Depressed Adolescents. Journal of clinical child and adolescent psychology Colich, N. L., Foland-Ross, L. C., Eggleston, C., Singh, M. K., Gotlib, I. H. 2016; 45 (1): 21-30

  Abstract

  Adults diagnosed with major depressive disorder (MDD) have been found to be characterized by selective attention to negative material and by impairments in their ability to disengage from, or inhibit the processing of, negative stimuli. Altered functioning in the frontal executive control network has been posited to underlie these deficits in cognitive functioning. We know little, however, about the neural underpinnings of inhibitory difficulties in depressed adolescents. We used functional magnetic resonance imaging in 18 adolescents diagnosed with MDD and 15 age- and gender-matched healthy controls (CTLs) while they performed a modified affective Go/No-Go task that was designed to measure inhibitory control in the presence of an emotional distractor. Participants were presented with either a happy or a sad face, followed by a go or a no-go target to which they either made or inhibited a motor response. A group (MDD, CTL) by valence (happy, sad) by condition (go, no-go) analysis of variance indicated that MDD adolescents showed attenuated BOLD response in the right dorsolateral prefrontal cortex (DLPFC) and in the occipital cortex bilaterally, to no-go targets that followed a sad, but not a happy, face. Adolescents diagnosed with MDD showed anomalous recruitment of prefrontal control regions during inhibition trials, suggesting depression-associated disruption in neural underpinnings of the inhibition of emotional distractors. Given that the DLPFC is associated with the maintenance of goal-relevant information, it is likely that sad faces differentially capture attention in adolescents with MDD and interfere with task demands requiring inhibition.

  View details for DOI 10.1080/15374416.2014.982281

  View details for PubMedID 25635920

  View details for PubMedCentralID PMC4520793

• The Importance of Assessing Neural Trajectories in Pediatric Depression JAMA PSYCHIATRY Gotlib, I. H., Ordaz, S. J. 2016; 73 (1): 9-10

  View details for DOI 10.1001/jamapsychiatry.2015.2453

  View details for Web of Science ID 000367820000004

  View details for PubMedID 26676653

• Concordant Patterns of Brain Structure in Mothers with Recurrent Depression and Their Never-Depressed Daughters DEVELOPMENTAL NEUROSCIENCE Foland-Ross, L. C., Behzadian, N., LeMoult, J., Gotlib, I. H. 2016; 38 (2): 115-123

  Abstract

  A growing body of research has demonstrated that having a mother with a history of major depressive disorder (MDD) is one of the strongest predictors of depression in adolescent offspring. Few studies, however, have assessed neural markers of this increased risk for depression, or examined whether risk-related anomalies in adolescents at maternal risk for depression are related to neural abnormalities in their depressed mothers. We addressed these questions by examining concordance in brain structure in two groups of participants: mothers with a history of depression and their never-depressed daughters, and never-depressed mothers and their never-depressed daughters.We scanned mothers with (remitted; RMD) and without (control; CTL) a history of recurrent episodes of depression and their never-depressed daughters, computed cortical gray matter thickness, and tested whether mothers' thickness predicted daughters' thickness.Both RMD mothers and their high-risk daughters exhibited focal areas of thinner cortical gray matter compared with their CTL/low-risk counterparts. Importantly, the extent of thickness anomalies in RMD mothers predicted analogous abnormalities in their daughters; this pattern was not present in CTL/low-risk dyads.We identified neuroanatomical risk factors that may underlie the intergenerational transmission of risk for MDD. Our findings suggest that there is concordance in brain structure in dyads that is affected by maternal depression, and that the location, direction, and extent of neural anomalies in high-risk offspring mirror those of their recurrent depressed mothers.

  View details for DOI 10.1159/000444448

  View details for Web of Science ID 000379162600004

  View details for PubMedID 27198667

  View details for PubMedCentralID PMC4927380

• Cortical thickness predicts the first onset of major depression in adolescence. International journal of developmental neuroscience Foland-Ross, L. C., Sacchet, M. D., Prasad, G., Gilbert, B., Thompson, P. M., Gotlib, I. H. 2015; 46: 125-131

  Abstract

  Given the increasing prevalence of Major Depressive Disorder and recent advances in preventative treatments for this disorder, an important challenge in pediatric neuroimaging is the early identification of individuals at risk for depression. We examined whether machine learning can be used to predict the onset of depression at the individual level. Thirty-three never-disordered adolescents (10-15 years old) underwent structural MRI. Participants were followed for 5 years to monitor the emergence of clinically significant depressive symptoms. We used support vector machines (SVMs) to test whether baseline cortical thickness could reliably distinguish adolescents who develop depression from adolescents who remained free of any Axis I disorder. Accuracies from subsampled cross-validated classification were used to assess classifier performance. Baseline cortical thickness correctly predicted the future onset of depression with an overall accuracy of 70% (69% sensitivity, 70% specificity; p=0.021). Examination of SVM feature weights indicated that the right medial orbitofrontal, right precentral, left anterior cingulate, and bilateral insular cortex contributed most strongly to this classification. These findings indicate that cortical gray matter structure can predict the subsequent onset of depression. An important direction for future research is to elucidate mechanisms by which these anomalies in gray matter structure increase risk for developing this disorder.

  View details for DOI 10.1016/j.ijdevneu.2015.07.007

  View details for PubMedID 26315399

• Rumination and Worry in Daily Life: Examining the Naturalistic Validity of Theoretical Constructs. Clinical psychological science : a journal of the Association for Psychological Science Kircanski, K., Thompson, R. J., Sorenson, J., Sherdell, L., Gotlib, I. H. 2015; 3 (6): 926-939

  Abstract

  Rumination and worry, two forms of perseverative thinking, hold promise as core processes that transect depressive and anxiety disorders. Whereas previous studies have been limited to the laboratory or to single diagnoses, we used experience sampling methods to assess and validate rumination and worry as transdiagnostic phenomena in the daily lives of individuals diagnosed with Major Depressive Disorder (MDD), Generalized Anxiety Disorder (GAD), and co-occurring MDD-GAD. Clinical and healthy control participants carried a hand-held electronic device for one week. Eight times per day they reported on their current levels of rumination and worry and their theoretically postulated features: thought unpleasantness, repetitiveness, abstractness, uncontrollability, temporal orientation, and content, and overall senses of certainty and control. Both rumination and worry emerged as transdiagnostic processes that cut across MDD, GAD, and MDD-GAD. Furthermore, most psychological theories concerning rumination and worry strongly mapped onto participants' reports, providing the first naturalistic validation of these constructs.

  View details for PubMedID 26783506

• Predicting first onset of depression in young girls: Interaction of diurnal cortisol and negative life events. Journal of abnormal psychology LeMoult, J., Ordaz, S. J., Kircanski, K., Singh, M. K., Gotlib, I. H. 2015; 124 (4): 850-859

  Abstract

  Interactions between biological vulnerability and environmental adversity are central to the pathophysiology of depression. Given evidence that the hypothalamic-pituitary-adrenal (HPA) axis influences biological responses to environmental events, in the current longitudinal study the authors examined HPA-axis functioning, negative life events, and their interaction as predictors of the first onset of depression. At baseline, girls ages 9 to 14 years provided saliva samples to assess levels of diurnal cortisol production, quantified by total cortisol production (area under the curve with respect to ground; AUCg) and the cortisol awakening response (CAR). The authors then followed these participants until they reached age 18 in order to assess their subsequent experience of negative life events and the onset of a depressive episode. They found that the influence of negative life events on the subsequent onset of depression depended on HPA-axis functioning at baseline. Specifically, negative life events predicted the onset of depression in girls with higher levels of AUCg, but not in girls with lower levels of AUCg. In contrast, CAR did not predict the onset of depression either alone or in interaction with negative life events. These findings suggest that elevated total cortisol production in daily life potentiates susceptibility to environmental adversity and signals the need for early intervention.

  View details for DOI 10.1037/abn0000087

  View details for PubMedID 26595472

  View details for PubMedCentralID PMC4662047

• A Neural Substrate for Behavioral Inhibition in the Risk for Major Depressive Disorder JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY Bellgowan, J. F., Molfese, P., Marx, M., Thomason, M., Glen, D., Santiago, J., Gotlib, I. H., Drevets, W. C., Hamilton, J. P. 2015; 54 (10): 841-848

  Abstract

  Behavioral inhibition (BI) is an early developing trait associated with cautiousness and development of clinical depression and anxiety. Little is known about the neural basis of BI and its predictive importance concerning risk for internalizing disorders. We looked at functional connectivity of the default-mode network (DMN) and salience network (SN), given their respective roles in self-relational and threat processing, in the risk for internalizing disorders, with an emphasis on determining the functional significance of these networks for BI.We used functional magnetic resonance imaging to scan, during the resting state, children and adolescents 8 to 17 years of age who were either at high familial risk (HR; n = 16) or low familial risk (LR; n = 18) for developing clinical depression and/or anxiety. Whole-brain DMN and SN functional connectivity were estimated for each participant and compared across groups. We also compared the LR and HR groups on levels of BI and anxiety, and incorporated these data into follow-up neurobehavioral correlation analyses.The HR group, relative to the LR group, showed significantly decreased DMN connectivity with the ventral striatum and bilateral sensorimotor cortices. Within the HR group, trait BI increased as DMN connectivity with the ventral striatum and sensorimotor cortex decreased. The HR and LR groups did not differ with respect to SN connectivity.Our findings show, in the risk for internalizing disorders, a negative functional relation between brain regions supporting self-relational processes and reward prediction. These findings represent a potential neural substrate for behavioral inhibition in the risk for clinical depression and anxiety.

  View details for DOI 10.1016/j.jaac.2015.08.001

  View details for Web of Science ID 000362056800012

• Emotional clarity as a function of neuroticism and major depressive disorder. Emotion Thompson, R. J., Kuppens, P., Mata, J., Jaeggi, S. M., Buschkuehl, M., Jonides, J., Gotlib, I. H. 2015; 15 (5): 615-624

  Abstract

  Investigators have begun to document links between emotional clarity and forms of negative emotionality, including neuroticism and major depressive disorder (MDD). Researchers to date have relied almost exclusively on global self-reports of emotional clarity; moreover, no studies have examined emotional clarity as a function of valence, although this may prove to be crucial in understanding the relation of emotional clarity to maladjustment. In 2 studies, we used experience-sampling methodology and multilevel modeling to examine the associations between emotional clarity and 2 constructs that have been linked theoretically with emotional clarity: neuroticism and depression. In Study 1 we assessed 95 college students who completed a self-report measure of neuroticism. In Study 2 we examined 53 adults diagnosed with MDD and 53 healthy adults. Reaction times to negative and positive emotion ratings during the experience-sampling protocols were used as an indirect measure of emotional clarity. Neuroticism was related to lower clarity of negative, but not of positive, emotion. Similarly, compared with the healthy controls, individuals with MDD had lower clarity of negative, but not of positive, emotion. It is important to note, findings from both studies held after controlling for baseline RTs and current levels of negative and positive emotion. These findings highlight the importance of assessing valence when examining emotional clarity and increase our understanding of the nature of the emotional disturbances that characterize neuroticism and MDD.

  View details for DOI 10.1037/emo0000067

  View details for PubMedID 25844973

  View details for PubMedCentralID PMC4586306

• A Neural Substrate for Behavioral Inhibition in the Risk for Major Depressive Disorder. Journal of the American Academy of Child and Adolescent Psychiatry Frost Bellgowan, J., Molfese, P., Marx, M., Thomason, M., Glen, D., Santiago, J., Gotlib, I. H., Drevets, W. C., Hamilton, J. P. 2015; 54 (10): 841-848

  Abstract

  Behavioral inhibition (BI) is an early developing trait associated with cautiousness and development of clinical depression and anxiety. Little is known about the neural basis of BI and its predictive importance concerning risk for internalizing disorders. We looked at functional connectivity of the default-mode network (DMN) and salience network (SN), given their respective roles in self-relational and threat processing, in the risk for internalizing disorders, with an emphasis on determining the functional significance of these networks for BI.We used functional magnetic resonance imaging to scan, during the resting state, children and adolescents 8 to 17 years of age who were either at high familial risk (HR; n = 16) or low familial risk (LR; n = 18) for developing clinical depression and/or anxiety. Whole-brain DMN and SN functional connectivity were estimated for each participant and compared across groups. We also compared the LR and HR groups on levels of BI and anxiety, and incorporated these data into follow-up neurobehavioral correlation analyses.The HR group, relative to the LR group, showed significantly decreased DMN connectivity with the ventral striatum and bilateral sensorimotor cortices. Within the HR group, trait BI increased as DMN connectivity with the ventral striatum and sensorimotor cortex decreased. The HR and LR groups did not differ with respect to SN connectivity.Our findings show, in the risk for internalizing disorders, a negative functional relation between brain regions supporting self-relational processes and reward prediction. These findings represent a potential neural substrate for behavioral inhibition in the risk for clinical depression and anxiety.

  View details for DOI 10.1016/j.jaac.2015.08.001

  View details for PubMedID 26407494

• Meta-analysis of Functional Neuroimaging of Major Depressive Disorder in Youth JAMA PSYCHIATRY Miller, C. H., Hamilton, J. P., Sacchet, M. D., Gotlib, I. H. 2015; 72 (10): 1045-1053

  Abstract

  Despite its high prevalence and morbidity, the underlying neural basis of major depressive disorder (MDD) in youth is not well understood.To identify in youth diagnosed as having MDD the most reliable neural abnormalities reported in existing functional neuroimaging studies and characterize their relations with specific psychological dysfunctions.Searches were conducted in PubMed and Web of Science to identify relevant studies published from November 2006 through February 2015. The current analysis took place from August 21, 2014, to March 28, 2015.We retained articles that conducted a comparison of youth aged 4 to 24 years diagnosed as having MDD and age-matched healthy controls using task-based functional magnetic resonance imaging and a voxelwise whole-brain approach.We extracted coordinates of brain regions exhibiting differential activity in youth with MDD compared with healthy control participants. Multilevel kernel density analysis was used to examine voxelwise between-group differences throughout the whole brain. Correction for multiple comparisons was performed by computing null hypothesis distributions from 10 000 Monte Carlo simulations and calculating the cluster size necessary to obtain the familywise error rate control at P < .05.Abnormal levels of activation in youth diagnosed as having MDD compared with control participants during a variety of affective processing and executive functioning tasks.Compared with age-matched healthy control participants (n = 274), youth with MDD (n = 246) showed reliable patterns of abnormal activation, including the following task-general and task-specific effects: hyperactivation in subgenual anterior cingulate cortex (P < .05) and ventrolateral prefrontal cortex (P < .05) and hypoactivation in caudate (P < .01) across aggregated tasks; hyperactivation in thalamus (P < .03) and parahippocampal gyrus (P < .003) during affective processing tasks; hypoactivation in cuneus (P < .001), dorsal cingulate cortex (P < .05), and dorsal anterior insula (P < .05) during executive functioning tasks; hypoactivity in posterior insula (P < .005) during positive valence tasks; and hyperactivity in dorsolateral prefrontal cortex (P < .001) and superior temporal cortex (P < .003) during negative valence tasks.Altered activations in several distributed brain networks may help explain the following seemingly disparate symptoms of MDD in youth: hypervigilance toward emotional stimuli from the overactivation of central hubs in the subgenual anterior cingulate cortex and thalamus that lead to a cascade of other symptoms; ineffective emotion regulation despite increased activation of the dorsolateral prefrontal cortex and ventrolateral prefrontal cortex during affective processing, which may reverse across development or the clinical course; maladaptive rumination and poor executive control from difficulties shifting from default mode network activity to task-positive network activity during cognitively demanding tasks; and anhedonia from hypoactivation of the cuneus and posterior insula during reward processing.

  View details for DOI 10.1001/jamapsychiatry.2015.1376

  View details for Web of Science ID 000362972000017

  View details for PubMedID 26332700

• Updating emotional content in recovered depressed individuals: Evaluating deficits in emotion processing following a depressive episode JOURNAL OF BEHAVIOR THERAPY AND EXPERIMENTAL PSYCHIATRY Levens, S. M., Gotlib, I. H. 2015; 48: 156-163

  Abstract

  Previous research has demonstrated that depressed individuals have difficulty both disengaging from negative information and maintaining positive information in working memory (WM). The present study was conducted to examine whether the tendency for depressed individuals to maintain negative content in WM and to experience difficulties maintaining positive content in WM is due to negative mood (in)congruency effects during a depressive episode, or whether these tendencies are evident outside of a depressive episode.Individuals who had recovered from a depressive episode and never disordered controls performed emotion 0-back and 2-back tasks designed to assess biases in updating emotional content in working memory.Similar to currently depressed individuals in previous studies, recovered depressed participants disengaged from happy stimuli more quickly and from sad stimuli more slowly than did their never-depressed counterparts.Despite the extension of a depression-specific finding to recovered depressed individuals, the present study does not test whether the identified emotion updating biases predict long-term relapse or recovery.The obtained results suggest that a decreased ability to disengage from negative content and to maintain positive content in WM represents a trait-like cognitive style that impairs adaptive emotion regulation and may contribute to the recurrent nature of depression.

  View details for DOI 10.1016/j.jbtep.2015.03.009

  View details for Web of Science ID 000355239600021

  View details for PubMedID 25889375

  View details for PubMedCentralID PMC4524779

• Intrinsic Amygdala Functional Connectivity in Youth With Bipolar I Disorder. Journal of the American Academy of Child and Adolescent Psychiatry Singh, M. K., Kelley, R. G., Chang, K. D., Gotlib, I. H. 2015; 54 (9): 763-770

  Abstract

  Bipolar disorder (BD) commonly begins during adolescence and may continue into adulthood. Studies in adults with BD suggest that disruptions in amygdalar neural circuitry explain the pathophysiology underlying the disorder. Importantly, however, amygdala subregion networks have not yet been examined in youth close to mania onset. The goal of this study was to compare resting state functional connectivity patterns in amygdala subregions in youth with bipolar I disorder with patterns in healthy controls.Centromedial, laterobasal, and superficial amygdala subdivisions were assessed during rest and examined in relation to clinical measures of mania in youth (14-20 years old) with bipolar I disorder who experienced only a single episode of mania (BD; n = 20) and age-matched healthy comparison youth without any personal or family history of DSM-IV Axis I disorders (HC; n = 23).Relative to HC youth, youth with BD exhibited decreased connectivity between the laterobasal subdivision of the amygdala and the hippocampus and precentral gyrus, and increased connectivity between the laterobasal subdivision and the precuneus. Connectivity between the right laterobasal amygdala and right hippocampus was positively correlated with levels of anxiety in BD but not in HC youth, and connectivity between the right laterobasal amygdala and right precuneus was negatively correlated with insight about bipolar illness.Youth with BD have abnormal amygdala resting state network connections to regions that are critical for emotional processing and self-awareness. Longitudinal studies are needed to determine whether these aberrant patterns in youth with BD can be altered with intervention and can influence the course of disorder.

  View details for DOI 10.1016/j.jaac.2015.06.016

  View details for PubMedID 26299298

• Influence of menarche on the relation between diurnal cortisol production and ventral striatum activity during reward anticipation. Social cognitive and affective neuroscience LeMoult, J., Colich, N. L., Sherdell, L., Hamilton, J. P., Gotlib, I. H. 2015; 10 (9): 1244-1250

  Abstract

  Adolescence is characterized by an increase in risk-taking and reward-seeking behaviors. In other populations, increased risk taking has been associated with tighter coupling between cortisol production and ventral striatum (VS) activation during reward anticipation; this relation has not yet been examined, however, as a function of adolescent development. This study examined the influence of pubertal development on the association between diurnal cortisol production and VS activity during reward anticipation. Pre- and post-menarcheal girls collected diurnal cortisol and completed an functional magnetic resonance imaging-based monetary incentive delay task, from which we extracted estimates of VS activity during the anticipation of reward, anticipation of loss and anticipation of non-incentive neutral trials. Post-menarcheal girls showed greater coupling between the cortisol awakening response and VS activation during anticipation of reward and loss than did their pre-menarcheal counterparts. Post-menarcheal girls did not differ from pre-menarcheal girls in their cortisol-VS coupling during anticipation of neutral trials, suggesting that puberty-related changes in cortisol-VS coupling are specific to affective stimuli. Interestingly, behavioral responses during the task indicate that post-menarcheal girls are faster to engage with affective stimuli than are pre-menarcheal girls. Thus, post-menarcheal girls exhibit neurobiological and behavioral patterns that have been associated with risk taking and that may underlie the dramatic increase in risk-taking behavior documented during adolescence.

  View details for DOI 10.1093/scan/nsv016

  View details for PubMedID 25678549

  View details for PubMedCentralID PMC4560950

• Subcortical volumes differentiate Major Depressive Disorder, Bipolar Disorder, and remitted Major Depressive Disorder JOURNAL OF PSYCHIATRIC RESEARCH Sacchet, M. D., Livermore, E. E., Iglesias, J. E., Glover, G. H., Gotlib, I. H. 2015; 68: 91-98

  Abstract

  Subcortical gray matter regions have been implicated in mood disorders, including Major Depressive Disorder (MDD) and Bipolar Disorder (BD). It is unclear, however, whether or how these regions differ among mood disorders and whether such abnormalities are state- or trait-like. In this study, we examined differences in subcortical gray matter volumes among euthymic BD, MDD, remitted MDD (RMD), and healthy (CTL) individuals. Using automated gray matter segmentation of T1-weighted MRI images, we estimated volumes of 16 major subcortical gray matter structures in 40 BD, 57 MDD, 35 RMD, and 61 CTL individuals. We used multivariate analysis of variance to examine group differences in these structures, and support vector machines (SVMs) to assess individual-by-individual classification. Analyses yielded significant group differences for caudate (p = 0.029) and ventral diencephalon (VD) volumes (p = 0.003). For the caudate, both the BD (p = 0.004) and the MDD (p = 0.037) participants had smaller volumes than did the CTL participants. For the VD, the MDD participants had larger volumes than did the BD and CTL participants (ps < 0.005). SVM distinguished MDD from BD with 59.5% accuracy. These findings indicate that mood disorders are characterized by anomalies in subcortical gray matter volumes and that the caudate and VD contribute uniquely to differential affective pathology. Identifying abnormalities in subcortical gray matter may prove useful for the prevention, diagnosis, and treatment of mood disorders.

  View details for DOI 10.1016/j.jpsychires.2015.06.002

  View details for Web of Science ID 000359956100015

  View details for PubMedID 26228406

• Intrinsic Amygdala Functional Connectivity in Youth With Bipolar I Disorder JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY Singh, M. K., Kelley, R. G., Chang, K. D., Gotlib, I. H. 2015; 54 (9): 763-770

  Abstract

  Bipolar disorder (BD) commonly begins during adolescence and may continue into adulthood. Studies in adults with BD suggest that disruptions in amygdalar neural circuitry explain the pathophysiology underlying the disorder. Importantly, however, amygdala subregion networks have not yet been examined in youth close to mania onset. The goal of this study was to compare resting state functional connectivity patterns in amygdala subregions in youth with bipolar I disorder with patterns in healthy controls.Centromedial, laterobasal, and superficial amygdala subdivisions were assessed during rest and examined in relation to clinical measures of mania in youth (14-20 years old) with bipolar I disorder who experienced only a single episode of mania (BD; n = 20) and age-matched healthy comparison youth without any personal or family history of DSM-IV Axis I disorders (HC; n = 23).Relative to HC youth, youth with BD exhibited decreased connectivity between the laterobasal subdivision of the amygdala and the hippocampus and precentral gyrus, and increased connectivity between the laterobasal subdivision and the precuneus. Connectivity between the right laterobasal amygdala and right hippocampus was positively correlated with levels of anxiety in BD but not in HC youth, and connectivity between the right laterobasal amygdala and right precuneus was negatively correlated with insight about bipolar illness.Youth with BD have abnormal amygdala resting state network connections to regions that are critical for emotional processing and self-awareness. Longitudinal studies are needed to determine whether these aberrant patterns in youth with BD can be altered with intervention and can influence the course of disorder.

  View details for DOI 10.1016/j.jaac.2015.06.016

  View details for Web of Science ID 000360259500011

  View details for PubMedCentralID PMC4548854

• Depressive Rumination, the Default-Mode Network, and the Dark Matter of Clinical Neuroscience BIOLOGICAL PSYCHIATRY Hamilton, J. P., Farmer, M., Fogelman, P., Gotlib, I. H. 2015; 78 (4): 224-230

  Abstract

  The intuitive association between self-focused rumination in major depressive disorder (MDD) and the self-referential operations performed by the brain's default-mode network (DMN) has prompted interest in examining the role of the DMN in MDD. In this article, we present meta-analytic findings showing reliably increased functional connectivity between the DMN and subgenual prefrontal cortex (sgPFC)-connectivity that often predicts levels of depressive rumination. We also present meta-analytic findings that, while there is reliably increased regional cerebral blood flow in sgPFC in MDD, no such abnormality has been reliably observed in nodes of the DMN. We then detail a model that integrates the body of research presented. In this model, we propose that increased functional connectivity between sgPFC and the DMN in MDD represents an integration of the self-referential processes supported by the DMN with the affectively laden, behavioral withdrawal processes associated with sgPFC-an integration that produces a functional neural ensemble well suited for depressive rumination and that, in MDD, abnormally taxes only sgPFC and not the DMN. This synthesis explains a broad array of existing data concerning the neural substrates of depressive rumination and provides an explicit account of functional abnormalities in sgPFC in MDD.

  View details for DOI 10.1016/j.biopsych.2015.02.020

  View details for Web of Science ID 000358084200008

  View details for PubMedCentralID PMC4524294

• Depressive Rumination, the Default-Mode Network, and the Dark Matter of Clinical Neuroscience. Biological psychiatry Hamilton, J. P., Farmer, M., Fogelman, P., Gotlib, I. H. 2015; 78 (4): 224-30

  Abstract

  The intuitive association between self-focused rumination in major depressive disorder (MDD) and the self-referential operations performed by the brain's default-mode network (DMN) has prompted interest in examining the role of the DMN in MDD. In this article, we present meta-analytic findings showing reliably increased functional connectivity between the DMN and subgenual prefrontal cortex (sgPFC)-connectivity that often predicts levels of depressive rumination. We also present meta-analytic findings that, while there is reliably increased regional cerebral blood flow in sgPFC in MDD, no such abnormality has been reliably observed in nodes of the DMN. We then detail a model that integrates the body of research presented. In this model, we propose that increased functional connectivity between sgPFC and the DMN in MDD represents an integration of the self-referential processes supported by the DMN with the affectively laden, behavioral withdrawal processes associated with sgPFC-an integration that produces a functional neural ensemble well suited for depressive rumination and that, in MDD, abnormally taxes only sgPFC and not the DMN. This synthesis explains a broad array of existing data concerning the neural substrates of depressive rumination and provides an explicit account of functional abnormalities in sgPFC in MDD.

  View details for DOI 10.1016/j.biopsych.2015.02.020

  View details for PubMedID 25861700

  View details for PubMedCentralID PMC4524294

• Neural Markers of Familial Risk for Depression: An Investigation of Cortical Thickness Abnormalities in Healthy Adolescent Daughters of Mothers With Recurrent Depression JOURNAL OF ABNORMAL PSYCHOLOGY Foland-Ross, L. C., Gilbert, B. L., Joormann, J., Gotlib, I. H. 2015; 124 (3): 476-485

  Abstract

  Having a mother with major depressive disorder (MDD) is one of the strongest predictors of depression in late adolescence and early adulthood. Despite this fact, we know little about the neural mechanisms involved in the intergenerational transmission of risk for depression. Twenty-eight never-disordered daughters of recurrent depressed mothers (high-risk) and 36 never-disordered daughters of never-depressed mothers (low-risk) were scanned using MRI. Scan data were processed to provide measurements of cortical gray matter thickness. A general linear model was conducted at each surface point to assess the main effect of familial risk on cortical structure as well as to explore the interaction of familial risk and age. High-risk girls exhibited significantly thinner cortical gray matter in the right fusiform gyrus relative to low-risk girls. Exploratory analyses indicated interactions of risk group and age in the bilateral anterior insula and right anterior cingulate cortex (ACC); whereas low-risk girls exhibited an inverse association between age and thickness, girls at high risk for depression showed the reverse pattern. Additional exploratory analyses, using scores on the Children's Sadness Management Scale, indicated that thinner gray matter in the ACC of high-risk girls was associated with greater difficulty in managing sadness. These findings indicate that anomalous reductions in the cortical thickness of the fusiform gyrus may be a marker of risk for MDD. The interaction of age and group for gray matter thickness of the insula and ACC suggests a particularly important role for these regions in risk for depression and warrants additional research in longitudinal studies. (PsycINFO Database Record

  View details for DOI 10.1037/abn0000050

  View details for Web of Science ID 000359379000002

  View details for PubMedCentralID PMC4573777

• Neural markers of familial risk for depression: An investigation of cortical thickness abnormalities in healthy adolescent daughters of mothers with recurrent depression. Journal of abnormal psychology Foland-Ross, L. C., Gilbert, B. L., Joormann, J., Gotlib, I. H. 2015; 124 (3): 476-485

  Abstract

  Having a mother with major depressive disorder (MDD) is one of the strongest predictors of depression in late adolescence and early adulthood. Despite this fact, we know little about the neural mechanisms involved in the intergenerational transmission of risk for depression. Twenty-eight never-disordered daughters of recurrent depressed mothers (high-risk) and 36 never-disordered daughters of never-depressed mothers (low-risk) were scanned using MRI. Scan data were processed to provide measurements of cortical gray matter thickness. A general linear model was conducted at each surface point to assess the main effect of familial risk on cortical structure as well as to explore the interaction of familial risk and age. High-risk girls exhibited significantly thinner cortical gray matter in the right fusiform gyrus relative to low-risk girls. Exploratory analyses indicated interactions of risk group and age in the bilateral anterior insula and right anterior cingulate cortex (ACC); whereas low-risk girls exhibited an inverse association between age and thickness, girls at high risk for depression showed the reverse pattern. Additional exploratory analyses, using scores on the Children's Sadness Management Scale, indicated that thinner gray matter in the ACC of high-risk girls was associated with greater difficulty in managing sadness. These findings indicate that anomalous reductions in the cortical thickness of the fusiform gyrus may be a marker of risk for MDD. The interaction of age and group for gray matter thickness of the insula and ACC suggests a particularly important role for these regions in risk for depression and warrants additional research in longitudinal studies. (PsycINFO Database Record

  View details for DOI 10.1037/abn0000050

  View details for PubMedID 25894441

• Processing of Emotional Information in Major Depressive Disorder: Toward a Dimensional Understanding EMOTION REVIEW Kircanski, K., Gotlib, I. H. 2015; 7 (3): 256-264

  View details for DOI 10.1177/1754073915575402

  View details for Web of Science ID 000357139300009

• HPA-axis reactivity interacts with stage of pubertal development to predict the onset of depression PSYCHONEUROENDOCRINOLOGY Colich, N. L., Kircanski, K., Foland-Ross, L. C., Gotlib, I. H. 2015; 55: 94-101

  Abstract

  Both elevated and blunted levels of cortisol secretion during childhood and adolescence have been linked to the subsequent onset of major depressive disorder (MDD). These mixed findings may be due to developmental changes in HPA-axis functioning, which have not been previously assessed in the context of risk. In the present study, therefore, we examined whether pubertal development moderated the influence of cortisol secretion on the subsequent development of MDD. Eighty-nine never-disordered girls ages 9-15 years, many of whom were at high risk for depression by virtue of having a maternal history of the disorder, completed a laboratory stress task. To index cortisol reactivity, salivary cortisol samples were collected at baseline and 15min following the onset of the stressor. Girls' levels of pubertal development were measured using Tanner staging. All participants were followed through age 18 in order to assess the subsequent development of MDD. Pubertal stage moderated the effects of cortisol stress reactivity on the development of MDD. Specifically, the onset of MDD was predicted by cortisol hyporeactivity in girls who were earlier in pubertal development (Tanner stage≤2), but by cortisol hyperreactivity in girls who were later in pubertal development (Tanner stage≥3.5).These findings demonstrate that girls' cortisol stress reactivity predicts the subsequent onset of MDD, and further, that the nature of this effect depends on the girls' level of pubertal development. Results are discussed in the context of clarifying previous findings, and directions for future research are offered.

  View details for DOI 10.1016/j.psyneuen.2015.02.004

  View details for Web of Science ID 000353090100009

  View details for PubMedCentralID PMC4380614

• Subcortical Volumes Differentiate Affective Disorders Sacchet, M. D., Livermore, E. E., Iglesias, J., Glover, G. H., Gotlib, I. H. ELSEVIER SCIENCE INC. 2015

  View details for Web of Science ID 000352207501256

• Young Girls' Autonomic Responses to Social Stress as a Function of Environmental Adversity and Familial Risk for Depression Price, A. N., Camacho, M. C., Kircanski, K., Gotlib, I. H. ELSEVIER SCIENCE INC. 2015: 139S

  View details for Web of Science ID 000352207500350

• Gonadal Hormones are Associated with Negative Emotion Reactivity and Regulation in Early Puberty Colich, N. L., Gotlib, I. H. ELSEVIER SCIENCE INC. 2015

  View details for Web of Science ID 000352207501121

• Anomalous Local Efficiency Dynamics of the Hippocampus in Adolescent Major Depressive Disorder: A Graph Analysis Ho, T. C., Sacchet, M. D., Connolly, C. G., Han, L. M., Blom, E., LeWinn, K. Z., Mobayed, N., Simmons, A. N., Gotlib, I. H., Yang, T. T. ELSEVIER SCIENCE INC. 2015

  View details for Web of Science ID 000352207501263

• The Role of Estradiol and Early Life Stress in the Emergence of Depressive Symptoms in Early Pubertal Females Popolizio, M. M., Colich, N. L., Gotlib, I. H. ELSEVIER SCIENCE INC. 2015: 380S–381S

  View details for Web of Science ID 000352207502240

• Reducing Cortisol Reactivity to Stress in Major Depressive Disorder: The Effects of Rumination-Reduction Training Schreiner, C., LeMoult, J., Gotlib, I. H. ELSEVIER SCIENCE INC. 2015: 381S

  View details for Web of Science ID 000352207502241

• Functional Neuroimaging of Major Depressive Disorder (MDD) in Youth: A Meta-Analysis Miller, C. H., Hamilton, J., Sacchet, M. D., Gotlib, I. H. ELSEVIER SCIENCE INC. 2015: 381S–382S

  View details for Web of Science ID 000352207502243

• HPA-axis reactivity interacts with stage of pubertal development to predict the onset of depression. Psychoneuroendocrinology Colich, N. L., Kircanski, K., Foland-Ross, L. C., Gotlib, I. H. 2015; 55: 94-101

  Abstract

  Both elevated and blunted levels of cortisol secretion during childhood and adolescence have been linked to the subsequent onset of major depressive disorder (MDD). These mixed findings may be due to developmental changes in HPA-axis functioning, which have not been previously assessed in the context of risk. In the present study, therefore, we examined whether pubertal development moderated the influence of cortisol secretion on the subsequent development of MDD. Eighty-nine never-disordered girls ages 9-15 years, many of whom were at high risk for depression by virtue of having a maternal history of the disorder, completed a laboratory stress task. To index cortisol reactivity, salivary cortisol samples were collected at baseline and 15min following the onset of the stressor. Girls' levels of pubertal development were measured using Tanner staging. All participants were followed through age 18 in order to assess the subsequent development of MDD. Pubertal stage moderated the effects of cortisol stress reactivity on the development of MDD. Specifically, the onset of MDD was predicted by cortisol hyporeactivity in girls who were earlier in pubertal development (Tanner stage≤2), but by cortisol hyperreactivity in girls who were later in pubertal development (Tanner stage≥3.5).These findings demonstrate that girls' cortisol stress reactivity predicts the subsequent onset of MDD, and further, that the nature of this effect depends on the girls' level of pubertal development. Results are discussed in the context of clarifying previous findings, and directions for future research are offered.

  View details for DOI 10.1016/j.psyneuen.2015.02.004

  View details for PubMedID 25745954

  View details for PubMedCentralID PMC4380614

• Concordance of mother-daughter diurnal cortisol production: Understanding the intergenerational transmission of risk for depression BIOLOGICAL PSYCHOLOGY LeMoult, J., Chen, M. C., Foland-Ross, L. C., Burley, H. W., Gotlib, I. H. 2015; 108: 98-104

  Abstract

  A growing body of research is demonstrating concordance between mother and child diurnal cortisol production. In the context of maternal history of depression, intergenerational concordance of cortisol production could contribute to hypercortisolemia in children of depressed mothers, which has been shown to increase risk for MDD. The current study is the first to examine concordance in diurnal cortisol production between mothers with a history of depression and their never-depressed, but high-risk, children. We collected salivary cortisol across 2 days from mothers with (remitted; RMD) and without (CTL) a history of recurrent episodes of depression and their never-depressed daughters. As expected, RMD mothers and their daughters both exhibited higher cortisol production than did their CTL counterparts. Moreover, both across and within groups, mothers' and daughters' cortisol production were directly coupled. These findings suggest that there is an intergenerational concordance in cortisol dysregulation that may contribute to hypercortisolemia in girls at familial risk for depression.

  View details for DOI 10.1016/j.biopsycho.2015.03.019

  View details for PubMedID 25862380

• Telomere length and cortisol reactivity in children of depressed mothers. Molecular psychiatry Gotlib, I. H., LeMoult, J., Colich, N. L., Foland-Ross, L. C., Hallmayer, J., Joormann, J., Lin, J., Wolkowitz, O. M. 2015; 20 (5): 615-620

  Abstract

  A growing body of research demonstrates that individuals diagnosed with major depressive disorder (MDD) are characterized by shortened telomere length, which has been posited to underlie the association between depression and increased instances of medical illness. The temporal nature of the relation between MDD and shortened telomere length, however, is not clear. Importantly, both MDD and telomere length have been associated independently with high levels of stress, implicating dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and anomalous levels of cortisol secretion in this relation. Despite these associations, no study has assessed telomere length or its relation with HPA-axis activity in individuals at risk for depression, before the onset of disorder. In the present study, we assessed cortisol levels in response to a laboratory stressor and telomere length in 97 healthy young daughters of mothers either with recurrent episodes of depression (i.e., daughters at familial risk for depression) or with no history of psychopathology. We found that daughters of depressed mothers had shorter telomeres than did daughters of never-depressed mothers and, further, that shorter telomeres were associated with greater cortisol reactivity to stress. This study is the first to demonstrate that children at familial risk of developing MDD are characterized by accelerated biological aging, operationalized as shortened telomere length, before they had experienced an onset of depression; this may predispose them to develop not only MDD but also other age-related medical illnesses. It is critical, therefore, that we attempt to identify and distinguish genetic and environmental mechanisms that contribute to telomere shortening.

  View details for DOI 10.1038/mp.2014.119

  View details for PubMedID 25266121

  View details for PubMedCentralID PMC4419149

• Attention to Emotional Information in Social Anxiety Disorder With and Without Co-Occurring Depression COGNITIVE THERAPY AND RESEARCH Kircanski, K., Joormann, J., Gotlib, I. H. 2015; 39 (2): 153-161

  View details for DOI 10.1007/s10608-014-9643-7

  View details for Web of Science ID 000351392500006

• Distinctive and common neural underpinnings of major depression, social anxiety, and their comorbidity. Social cognitive and affective neuroscience Hamilton, J. P., Chen, M. C., Waugh, C. E., Joormann, J., Gotlib, I. H. 2015; 10 (4): 552-560

  Abstract

  Assessing neural commonalities and differences among depression, anxiety and their comorbidity is critical in developing a more integrative clinical neuroscience and in evaluating currently debated categorical vs dimensional approaches to psychiatric classification. Therefore, in this study, we sought to identify patterns of anomalous neural responding to criticism and praise that are specific to and common among major depressive disorder (MDD), social anxiety disorder (SAD) and comorbid MDD-SAD. Adult females who met formal diagnostic criteria for MDD, SAD or MDD-SAD and psychiatrically healthy participants underwent functional magnetic resonance imaging as they listened to statements directing praise or criticism at them or at another person. MDD groups showed reduced responding to praise across a distributed cortical network, an effect potentially mediated by thalamic nuclei undergirding arousal-mediated attention. SAD groups showed heightened anterior insula and decreased default-mode network response to criticism. The MDD-SAD group uniquely showed reduced responding to praise in the dorsal anterior cingulate cortex. Finally, all groups with psychopathology showed heightened response to criticism in a region of the superior frontal gyrus implicated in attentional gating. The present results suggest novel neural models of anhedonia in MDD, vigilance-withdrawal behaviors in SAD, and poorer outcome in MDD-SAD. Importantly, in identifying unique and common neural substrates of MDD and SAD, these results support a formulation in which common neural components represent general risk factors for psychopathology that, due to factors that are present at illness onset, lead to distinct forms of psychopathology with unique neural signatures.

  View details for DOI 10.1093/scan/nsu084

  View details for PubMedID 25038225

• Identification of a direct GABAergic pallidocortical pathway in rodents EUROPEAN JOURNAL OF NEUROSCIENCE Chen, M. C., Ferrari, L., Sacchet, M. D., Foland-Ross, L. C., Qiu, M., Gotlib, I. H., Fuller, P. M., Arrigoni, E., Lu, J. 2015; 41 (6): 748-759

  Abstract

  Interaction between the basal ganglia and the cortex plays a critical role in a range of behaviors. Output from the basal ganglia to the cortex is thought to be relayed through the thalamus, but an intriguing alternative is that the basal ganglia may directly project to and communicate with the cortex. We explored an efferent projection from the globus pallidus externa (GPe), a key hub in the basal ganglia system, to the cortex of rats and mice. Anterograde and retrograde tracing revealed projections to the frontal premotor cortex, especially the deep projecting layers, originating from GPe neurons that receive axonal inputs from the dorsal striatum. Cre-dependent anterograde tracing in Vgat-ires-cre mice confirmed that the pallidocortical projection is GABAergic, and in vitro optogenetic stimulation in the cortex of these projections produced a fast inhibitory postsynaptic current in targeted cells that was abolished by bicuculline. The pallidocortical projections targeted GABAergic interneurons and, to a lesser extent, pyramidal neurons. This GABAergic pallidocortical pathway directly links the basal ganglia and cortex, and may play a key role in behavior and cognition in normal and disease states.

  View details for DOI 10.1111/ejn.12822

  View details for Web of Science ID 000351439000002

  View details for PubMedID 25581560

  View details for PubMedCentralID PMC4363158

• Emotion-Network Density in Major Depressive Disorder CLINICAL PSYCHOLOGICAL SCIENCE Pe, M., Kircanski, K., Thompson, R. J., Bringmann, L. F., Tuerlinckx, F., Mestdagh, M., Mata, J., Jaeggi, S. M., Buschkuehl, M., Jonides, J., Kuppens, P., Gotlib, I. H. 2015; 3 (2): 292–300

  View details for DOI 10.1177/2167702614540645

  View details for Web of Science ID 000409477000011

• Emotion-Network Density in Major Depressive Disorder. Clinical psychological science : a journal of the Association for Psychological Science Lee Pe, M., Kircanski, K., Thompson, R. J., Bringmann, L. F., Tuerlinckx, F., Mestdagh, M., Mata, J., Jaeggi, S. M., Buschkuehl, M., Jonides, J., Kuppens, P., Gotlib, I. H. 2015; 3 (2): 292-300

  Abstract

  Major Depressive Disorder (MDD) is a prevalent disorder involving disturbances in mood. There is still much to understand regarding precisely how emotions are disrupted in individuals with MDD. In this study, we used a network approach to examine the emotional disturbances underlying MDD. We hypothesized that, compared to healthy controls, individuals diagnosed with MDD would be characterized by a denser emotion network, indicating that their emotion system is more resistant to change. Indeed, results from a 7-day experience sampling study revealed that individuals with MDD had a denser overall emotion network than did healthy controls. Moreover, this difference was driven primarily by a denser negative, but not positive, network in MDD participants. These findings suggest that the disruption in emotions that characterizes depressed individuals stems from a negative emotion system that is resistant to change.

  View details for DOI 10.1177/2167702614540645

  View details for PubMedID 31754552

  View details for PubMedCentralID PMC6871506

• Support vector machine classification of major depressive disorder using diffusion-weighted neuroimaging and graph theory FRONTIERS IN PSYCHIATRY Sacchet, M. D., Prasad, G., Foland-Ross, L. C., Thompson, P. M., Gotlib, I. H. 2015; 6

  Abstract

  Recently, there has been considerable interest in understanding brain networks in major depressive disorder (MDD). Neural pathways can be tracked in the living brain using diffusion-weighted imaging (DWI); graph theory can then be used to study properties of the resulting fiber networks. To date, global abnormalities have not been reported in tractography-based graph metrics in MDD, so we used a machine learning approach based on "support vector machines" to differentiate depressed from healthy individuals based on multiple brain network properties. We also assessed how important specific graph metrics were for this differentiation. Finally, we conducted a local graph analysis to identify abnormal connectivity at specific nodes of the network. We were able to classify depression using whole-brain graph metrics. Small-worldness was the most useful graph metric for classification. The right pars orbitalis, right inferior parietal cortex, and left rostral anterior cingulate all showed abnormal network connectivity in MDD. This is the first use of structural global graph metrics to classify depressed individuals. These findings highlight the importance of future research to understand network properties in depression across imaging modalities, improve classification results, and relate network alterations to psychiatric symptoms, medication, and comorbidities.

  View details for DOI 10.3389/fpsyt.2015.00021

  View details for Web of Science ID 000364204500001

  View details for PubMedCentralID PMC4332161

• The impact of depression on Veterans with PTSD and traumatic brain injury: A diffusion tensor imaging study. Biological psychology Isaac, L., Main, K. L., Soman, S., Gotlib, I. H., Furst, A. J., Kinoshita, L. M., Fairchild, J. K., Yesavage, J. A., Ashford, J. W., Bayley, P. J., Adamson, M. M. 2015; 105: 20-28

  Abstract

  A significant proportion of military personnel deployed in support of Operation Enduring Freedom and Operation Iraqi Freedom were exposed to war-zone events associated with traumatic brain injury (TBI), depression (DEP) and posttraumatic stress disorder (PTSD). The co-occurrence of TBI, PTSD and DEP in returning Veterans has recently increased research and clinical interest. This study tested the hypothesis that white matter abnormalities are further impacted by depression. Of particular relevance is the uncinate fasciculus (UF), which is a key fronto-temporal tract involved in mood regulation, and the cingulum; a tract that connects to the hippocampus involved in memory integration. Diffusion tensor imaging (DTI) was performed on 25 patients with a combination of PTSD, TBI and DEP and 20 patients with PTSD and TBI (no DEP). Microstructural changes of white matter were found in the cingulum and UF. Fractional anisotropy (FA) was lower in Veterans with DEP compared to those without DEP.

  View details for DOI 10.1016/j.biopsycho.2014.12.011

  View details for PubMedID 25559772

• Support vector machine classification of major depressive disorder using diffusion-weighted neuroimaging and graph theory. Frontiers in psychiatry Sacchet, M. D., Prasad, G., Foland-Ross, L. C., Thompson, P. M., Gotlib, I. H. 2015; 6: 21-?

  Abstract

  Recently, there has been considerable interest in understanding brain networks in major depressive disorder (MDD). Neural pathways can be tracked in the living brain using diffusion-weighted imaging (DWI); graph theory can then be used to study properties of the resulting fiber networks. To date, global abnormalities have not been reported in tractography-based graph metrics in MDD, so we used a machine learning approach based on "support vector machines" to differentiate depressed from healthy individuals based on multiple brain network properties. We also assessed how important specific graph metrics were for this differentiation. Finally, we conducted a local graph analysis to identify abnormal connectivity at specific nodes of the network. We were able to classify depression using whole-brain graph metrics. Small-worldness was the most useful graph metric for classification. The right pars orbitalis, right inferior parietal cortex, and left rostral anterior cingulate all showed abnormal network connectivity in MDD. This is the first use of structural global graph metrics to classify depressed individuals. These findings highlight the importance of future research to understand network properties in depression across imaging modalities, improve classification results, and relate network alterations to psychiatric symptoms, medication, and comorbidities.

  View details for DOI 10.3389/fpsyt.2015.00021

  View details for PubMedID 25762941

  View details for PubMedCentralID PMC4332161

• Cognitive-Processing Biases in Individuals High on Perceived Criticism CLINICAL PSYCHOLOGICAL SCIENCE Masland, S. R., Hooley, J. M., Tully, L. M., Dearing, K., Gotlib, I. H. 2015; 3 (1): 3–14

  View details for DOI 10.1177/2167702614529935

  View details for Web of Science ID 000409473100001

• Cognitive Bias Modification for Interpretation in Major Depression: Effects on Memory and Stress Reactivity. Clinical psychological science : a journal of the Association for Psychological Science Joormann, J., Waugh, C. E., Gotlib, I. H. 2015; 3 (1): 126-139

  Abstract

  Interpreting ambiguous stimuli in a negative manner is a core bias associated with depression. Investigators have used cognitive bias modification for interpretation (CBM-I) to demonstrate that it is possible to experimentally induce and modify these biases. This study extends previous research by examining whether CBM-I affects not only interpretation, but also memory and physiological stress response in individuals diagnosed with Major Depressive Disorder (MDD). We found that CBM-I was effective in inducing an interpretive bias. Participants also exhibited memory biases that corresponded to their training condition and demonstrated differential physiological responding in a stress task. These results suggest that interpretation biases in depression can be modified, and that this training can lead to corresponding changes in memory and to decreases in stress reactivity. Findings from this study highlight the importance of examining the relations among different cognitive biases in MDD and the possibility of modifying cognitive biases.

  View details for PubMedID 25593790

• The role of the medial frontal cortex in the maintenance of emotional states SOCIAL COGNITIVE AND AFFECTIVE NEUROSCIENCE Waugh, C. E., Lemus, M. G., Gotlib, I. H. 2014; 9 (12): 2001-2009

  Abstract

  Evidence is accruing that people can maintain their emotional states, but how they do it and which brain regions are responsible still remains unclear. We examined whether people maintain emotional states 'actively', with explicit elaboration of the emotion, or 'passively', without elaboration. Twenty-four participants completed an emotion maintenance task in which they either maintained the emotional intensity from the first picture of a pair to compare to that of the second picture ('maintain' condition), or only rated their emotional response to the second picture ('non-maintain' condition). Supporting the 'active' maintenance hypothesis, when maintaining vs not maintaining emotion, participants exhibited increased height and width of activation in the dorsal medial frontal cortex (MFC) and lateral prefrontal cortex, regions associated with explicit emotion generation and manipulation of contents in working memory, respectively. Supporting the 'passive' maintenance hypothesis, however, when viewing negative emotional pictures (vs neutral pictures) that were not explicitly maintained, participants exhibited greater duration of activity in the rostral MFC, a region associated with implicit emotion generation. Supported by behavioral findings, this evidence that people maintain emotional states both naturally in the rMFC and strategically in the dMFC may be critical for understanding normal as well as disordered emotion regulation.

  View details for DOI 10.1093/scan/nsu011

  View details for Web of Science ID 000350105900017

  View details for PubMedID 24493835

  View details for PubMedCentralID PMC4249480

• Coping with having a depressed mother: The role of stress and coping in hypothalamic-pituitary-adrenal axis dysfunction in girls at familial risk for major depression DEVELOPMENT AND PSYCHOPATHOLOGY Foland-Ross, L. C., Kircanski, K., Gotlib, I. H. 2014; 26 (4): 1401-1409

  Abstract

  Having a depressed mother is one of the strongest predictors of depression in adolescence. We investigated whether the stress of having a mother with recurrent depression is associated with dysfunction in adolescents in the HPA axis and whether the tendency to use involuntary coping strategies in dealing with this stress is associated with exacerbation of dysfunction in this system. Sixty-four never-disordered daughters of mothers with recurrent depression (high risk) and 64 never-disordered daughters of never-disordered mothers (low risk) completed diurnal cortisol and stress assessments. High-risk girls secreted more diurnal cortisol than did low-risk girls. Whereas low-risk girls secreted higher levels of cortisol with increasing stress associated with having a depressed mother, no such relation was present in high-risk girls. Finally, in contrast to low-risk girls, girls at familial risk for depression who more frequently used involuntary versus voluntary coping exhibited the greatest elevations in diurnal cortisol. These findings indicate that a tendency to utilize involuntary, as opposed to voluntary, coping strategies in dealing with stress involving maternal depression exacerbates already high levels of cortisol in youth at risk for depression. Future research that examines whether interventions aimed at increasing the use of voluntary coping strategies normalizes HPA axis dysfunction is of interest.

  View details for DOI 10.1017/S0954579414001102

  View details for Web of Science ID 000345576500016

• The neuroscience of depression: implications for assessment and intervention. Behaviour research and therapy Singh, M. K., Gotlib, I. H. 2014; 62: 60-73

  Abstract

  Major Depressive Disorder (MDD) is among the most prevalent of all psychiatric disorders and is the single most burdensome disease worldwide. In attempting to understand the profound deficits that characterize MDD across multiple domains of functioning, researchers have identified aberrations in brain structure and function in individuals diagnosed with this disorder. In this review we synthesize recent data from human neuroimaging studies in presenting an integrated neural network framework for understanding the impairments experienced by individuals with MDD. We discuss the implications of these findings for assessment of and intervention for MDD. We conclude by offering directions for future research that we believe will advance our understanding of neural factors that contribute to the etiology and course of depression, and to recovery from this debilitating disorder.

  View details for DOI 10.1016/j.brat.2014.08.008

  View details for PubMedID 25239242

  View details for PubMedCentralID PMC4253641

• Coping with having a depressed mother: the role of stress and coping in hypothalamic-pituitary-adrenal axis dysfunction in girls at familial risk for major depression. Development and psychopathology Foland-Ross, L. C., Kircanski, K., Gotlib, I. H. 2014; 26 (4): 1401-1409

  Abstract

  Having a depressed mother is one of the strongest predictors of depression in adolescence. We investigated whether the stress of having a mother with recurrent depression is associated with dysfunction in adolescents in the HPA axis and whether the tendency to use involuntary coping strategies in dealing with this stress is associated with exacerbation of dysfunction in this system. Sixty-four never-disordered daughters of mothers with recurrent depression (high risk) and 64 never-disordered daughters of never-disordered mothers (low risk) completed diurnal cortisol and stress assessments. High-risk girls secreted more diurnal cortisol than did low-risk girls. Whereas low-risk girls secreted higher levels of cortisol with increasing stress associated with having a depressed mother, no such relation was present in high-risk girls. Finally, in contrast to low-risk girls, girls at familial risk for depression who more frequently used involuntary versus voluntary coping exhibited the greatest elevations in diurnal cortisol. These findings indicate that a tendency to utilize involuntary, as opposed to voluntary, coping strategies in dealing with stress involving maternal depression exacerbates already high levels of cortisol in youth at risk for depression. Future research that examines whether interventions aimed at increasing the use of voluntary coping strategies normalizes HPA axis dysfunction is of interest.

  View details for DOI 10.1017/S0954579414001102

  View details for PubMedID 25422969

• Early signs of anomalous neural functional connectivity in healthy offspring of parents with bipolar disorder. Bipolar disorders Singh, M. K., Chang, K. D., Kelley, R. G., Saggar, M., Reiss, A. L., Gotlib, I. H. 2014; 16 (7): 678-689

  Abstract

  Bipolar disorder (BD) has been associated with dysfunctional brain connectivity and with family chaos. It is not known whether aberrant connectivity occurs before illness onset, representing vulnerability for developing BD amidst family chaos. We used resting-state functional magnetic resonance imaging (fMRI) to examine neural network dysfunction in healthy offspring living with parents with BD and healthy comparison youth.Using two complementary methodologies [data-driven independent component analysis (ICA) and hypothesis-driven region-of-interest (ROI)-based intrinsic connectivity], we examined resting-state fMRI data in 8-17-year-old healthy offspring of a parent with BD (n = 24; high risk) and age-matched healthy youth without any personal or family psychopathology (n = 25; low risk).ICA revealed that, relative to low-risk youth, high-risk youth showed increased connectivity in the ventrolateral prefrontal cortex (VLPFC) subregion of the left executive control network (ECN), which includes frontoparietal regions important for emotion regulation. ROI-based analyses revealed that high-risk versus low-risk youth had decreased connectivities between the left amygdala and pregenual cingulate, between the subgenual cingulate and supplementary motor cortex, and between the left VLPFC and left caudate. High-risk youth showed stronger connections in the VLPFC with age and higher functioning, which may be neuroprotective, and weaker connections between the left VLPFC and caudate with more family chaos, suggesting an environmental influence on frontostriatal connectivity.Healthy offspring of parents with BD show atypical patterns of prefrontal and subcortical intrinsic connectivity that may be early markers of resilience to or vulnerability for developing BD. Longitudinal studies are needed to determine whether these patterns predict outcomes.

  View details for DOI 10.1111/bdi.12221

  View details for PubMedID 24938878

• The neuroscience of depression: Implications for assessment and intervention BEHAVIOUR RESEARCH AND THERAPY Singh, M. K., Gotlib, I. H. 2014; 62: 60-73

  Abstract

  Major Depressive Disorder (MDD) is among the most prevalent of all psychiatric disorders and is the single most burdensome disease worldwide. In attempting to understand the profound deficits that characterize MDD across multiple domains of functioning, researchers have identified aberrations in brain structure and function in individuals diagnosed with this disorder. In this review we synthesize recent data from human neuroimaging studies in presenting an integrated neural network framework for understanding the impairments experienced by individuals with MDD. We discuss the implications of these findings for assessment of and intervention for MDD. We conclude by offering directions for future research that we believe will advance our understanding of neural factors that contribute to the etiology and course of depression, and to recovery from this debilitating disorder.

  View details for DOI 10.1016/j.brat.2014.08.008

  View details for Web of Science ID 000345471000007

  View details for PubMedCentralID PMC4253641

• Early signs of anomalous neural functional connectivity in healthy offspring of parents with bipolar disorder BIPOLAR DISORDERS Singh, M. K., Chang, K. D., Kelley, R. G., Saggar, M., Reiss, A. L., Gotlib, I. H. 2014; 16 (7): 678-689

  Abstract

  Bipolar disorder (BD) has been associated with dysfunctional brain connectivity and with family chaos. It is not known whether aberrant connectivity occurs before illness onset, representing vulnerability for developing BD amidst family chaos. We used resting-state functional magnetic resonance imaging (fMRI) to examine neural network dysfunction in healthy offspring living with parents with BD and healthy comparison youth.Using two complementary methodologies [data-driven independent component analysis (ICA) and hypothesis-driven region-of-interest (ROI)-based intrinsic connectivity], we examined resting-state fMRI data in 8-17-year-old healthy offspring of a parent with BD (n = 24; high risk) and age-matched healthy youth without any personal or family psychopathology (n = 25; low risk).ICA revealed that, relative to low-risk youth, high-risk youth showed increased connectivity in the ventrolateral prefrontal cortex (VLPFC) subregion of the left executive control network (ECN), which includes frontoparietal regions important for emotion regulation. ROI-based analyses revealed that high-risk versus low-risk youth had decreased connectivities between the left amygdala and pregenual cingulate, between the subgenual cingulate and supplementary motor cortex, and between the left VLPFC and left caudate. High-risk youth showed stronger connections in the VLPFC with age and higher functioning, which may be neuroprotective, and weaker connections between the left VLPFC and caudate with more family chaos, suggesting an environmental influence on frontostriatal connectivity.Healthy offspring of parents with BD show atypical patterns of prefrontal and subcortical intrinsic connectivity that may be early markers of resilience to or vulnerability for developing BD. Longitudinal studies are needed to determine whether these patterns predict outcomes.

  View details for DOI 10.1111/bdi.12221

  View details for Web of Science ID 000344373100002

• Reward Processing in Healthy Offspring of Parents With Bipolar Disorder JAMA PSYCHIATRY Singh, M. K., Kelley, R. G., Howe, M. E., Reiss, A. L., Gotlib, I. H., Chang, K. D. 2014; 71 (10): 1148-1156

  Abstract

  Bipolar disorder (BD) is highly familial and characterized by deficits in reward processing. It is not known, however, whether these deficits precede illness onset or are a consequence of the disorder.To determine whether anomalous neural processing of reward characterizes children at familial risk for BD in the absence of a personal history of a psychopathologic disorder.This study compared neural activity and behaviors of children at high and low risk for mania while they anticipate and respond to reward and loss. The study was performed from September 15, 2009, through February 17, 2012, in a university functional magnetic resonance imaging facility and included 8- to 15-year-old children without disorders born to a parent with BD (n = 20 high-risk children) and demographically matched healthy comparison children (n = 25 low-risk children).Neural activity, as measured with functional magnetic resonance imaging, during anticipation and receipt of reward and loss during a monetary incentive delay task.While anticipating losses, high-risk children had less activation in the pregenual cingulate than did their low-risk counterparts (t19 = -2.44, P = .02). When receiving rewards, high-risk children had greater activation in the left lateral orbitofrontal cortex than did low-risk children (t43 = -3.04, P = .004). High-risk children also had weaker functional connectivity between the pregenual cingulate and the right ventrolateral prefrontal cortex while anticipating rewards than did low-risk children (t19 = -4.38, P < .001) but had a stronger connectivity between these regions while anticipating losses (t24 = 2.76, P = .01). Finally, in high- but not low-risk children, novelty seeking was associated with increased striatal and amygdalar activation in the anticipation of losses, and impulsivity was associated with increased striatal and insula activation in the receipt of rewards.Aberrant prefrontal activations and connectivities during reward processing suggest mechanisms that underlie early vulnerabilities for developing dysfunctional regulation of goal pursuit and motivation in children at high risk for mania. Longitudinal studies are needed to examine whether these patterns of neural activation predict the onset of mania and other mood disorders in high-risk children.

  View details for DOI 10.1001/jamapsychiatry.2014.1031

  View details for Web of Science ID 000342900200009

• Reward processing in healthy offspring of parents with bipolar disorder. JAMA psychiatry Singh, M. K., Kelley, R. G., Howe, M. E., Reiss, A. L., Gotlib, I. H., Chang, K. D. 2014; 71 (10): 1148-1156

  Abstract

  Bipolar disorder (BD) is highly familial and characterized by deficits in reward processing. It is not known, however, whether these deficits precede illness onset or are a consequence of the disorder.To determine whether anomalous neural processing of reward characterizes children at familial risk for BD in the absence of a personal history of a psychopathologic disorder.This study compared neural activity and behaviors of children at high and low risk for mania while they anticipate and respond to reward and loss. The study was performed from September 15, 2009, through February 17, 2012, in a university functional magnetic resonance imaging facility and included 8- to 15-year-old children without disorders born to a parent with BD (n = 20 high-risk children) and demographically matched healthy comparison children (n = 25 low-risk children).Neural activity, as measured with functional magnetic resonance imaging, during anticipation and receipt of reward and loss during a monetary incentive delay task.While anticipating losses, high-risk children had less activation in the pregenual cingulate than did their low-risk counterparts (t19 = -2.44, P = .02). When receiving rewards, high-risk children had greater activation in the left lateral orbitofrontal cortex than did low-risk children (t43 = -3.04, P = .004). High-risk children also had weaker functional connectivity between the pregenual cingulate and the right ventrolateral prefrontal cortex while anticipating rewards than did low-risk children (t19 = -4.38, P < .001) but had a stronger connectivity between these regions while anticipating losses (t24 = 2.76, P = .01). Finally, in high- but not low-risk children, novelty seeking was associated with increased striatal and amygdalar activation in the anticipation of losses, and impulsivity was associated with increased striatal and insula activation in the receipt of rewards.Aberrant prefrontal activations and connectivities during reward processing suggest mechanisms that underlie early vulnerabilities for developing dysfunctional regulation of goal pursuit and motivation in children at high risk for mania. Longitudinal studies are needed to examine whether these patterns of neural activation predict the onset of mania and other mood disorders in high-risk children.

  View details for DOI 10.1001/jamapsychiatry.2014.1031

  View details for PubMedID 25142103

• The "Ins" and "Outs" of the Depressive Disorders Section of DSM-5 CLINICAL PSYCHOLOGY-SCIENCE AND PRACTICE Gotlib, I. H., LeMoult, J. 2014; 21 (3): 193-207

  View details for DOI 10.1111/cpsp.12072

  View details for Web of Science ID 000343010700001

• Melancholia in later life: late and early onset differences in presentation, course, and dementia risk INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY Sachs-Ericsson, N., Moxley, J. H., Corsentino, E., Rushing, N. C., Sheffler, J., Selby, E. A., Gotlib, I., Steffens, D. C. 2014; 29 (9): 943-951

  Abstract

  Depression is a risk factor for cognitive decline and dementia. This risk may vary with age of onset and depression subtype. Late onset depression (LOD, 60 years and older) is associated with more cognitive decline, whereas early onset depression (EOD, before 60 years) is associated with more residual depressive symptoms. Potential differences may reflect divergent etiologies. These onset differences, however, have not been examined in the melancholic subtype of depression in older adults.Data were obtained from the Neurocognitive Outcomes of Depression in the Elderly study. Participants (N = 284, 73% EOD-melancholic (EOD-M) and 27% LOD-melancholic (LOD-M)) were followed up over 3 years. Factor analyses examined differences in baseline depressive symptoms. Hierarchical linear growth curve models examined changes in depressive symptoms (Montgomery-Asberg Depression Rating Scale) and cognition (mini mental state examination). An annual clinical review panel assigned diagnoses of dementia.The LOD-M participants had more vegetative symptoms at baseline. LOD-M exhibited greater cognitive decline but fewer residual depressive symptoms than EOD-M. Among participants who remained in the study for at least 1 year, in uncontrolled analyses, a greater percentage of LOD-M compared with EOD-M developed dementia (23.0% vs. 7.8%). Whereas in logistic analyses, controlling for baseline demographics, age at onset remained a predictor of dementia, the odds ratio suggested that the effect was relatively small.The EOD-M and LOD-M participants have a different presentation and course. LOD-M may represent a syndrome of neuropsychiatric deterioration with expression of both depressive symptoms and cognitive decline.

  View details for DOI 10.1002/gps.4083

  View details for Web of Science ID 000340573400009

  View details for PubMedID 24677247

• Increased Coupling of Intrinsic Networks in Remitted Depressed Youth Predicts Rumination and Cognitive Control PLOS ONE Jacobs, R. H., Jenkins, L. M., Gabriel, L. B., Barba, A., Ryan, K. A., Weisenbach, S. L., Verges, A., Baker, A. M., Peters, A. T., Crane, N. A., Gotlib, I. H., Zubieta, J., Phan, K. L., Langenecker, S. A., Welsh, R. C. 2014; 9 (8)

  Abstract

  Functional connectivity MRI (fcMRI) studies of individuals currently diagnosed with major depressive disorder (MDD) document hyperconnectivities within the default mode network (DMN) and between the DMN and salience networks (SN) with regions of the cognitive control network (CCN). Studies of individuals in the remitted state are needed to address whether effects derive from trait, and not state or chronic burden features of MDD.fcMRI data from two 3.0 Tesla GE scanners were collected from 30 unmedicated (47% medication naïve) youth (aged 18-23, modal depressive episodes = 1, mean age of onset = 16.2, SD = 2.6) with remitted MDD (rMDD; modal years well = 4) and compared with data from 23 healthy controls (HCs) using four bilateral seeds in the DMN and SN (posterior cingulate cortex (PCC), subgenual anterior cingulate (sgACC), and amygdala), followed by voxel-based comparisons of the whole brain.Compared to HCs, rMDD youth exhibited hyperconnectivities from both PCC and sgACC seeds with lateral, parietal, and frontal regions of the CCN, extending to the dorsal medial wall. A factor analysis reduced extracted data and a PCC factor was inversely correlated with rumination among rMDD youth. Two factors from the sgACC hyperconnectivity clusters were related to performance in cognitive control on a Go/NoGo task, one positively and one inversely.Findings document hyperconnectivities of the DMN and SN with the CCN (BA 8/10), which were related to rumination and sustained attention. Given these cognitive markers are known predictors of response and relapse, hyperconnectivities may increase relapse risk or represent compensatory mechanisms.

  View details for DOI 10.1371/journal.pone.0104366

  View details for Web of Science ID 000340880900012

  View details for PubMedID 25162661

  View details for PubMedCentralID PMC4146466

• Recalling happy memories in remitted depression: A neuroimaging investigation of the repair of sad mood COGNITIVE AFFECTIVE & BEHAVIORAL NEUROSCIENCE Foland-Ross, L. C., Cooney, R. E., Joormann, J., Henry, M. L., Gotlib, I. H. 2014; 14 (2): 818-826

  Abstract

  Major depressive disorder (MDD) is a recurrent mood disorder. The high rate of recurrence of MDD suggests the presence of stable vulnerability factors that place individuals with a history of major depression at an increased risk for the onset of another episode. Previous research has linked the remitted state, and therefore increased vulnerability for depressive relapse, with difficulties in the use of pleasant autobiographical memories to repair sad mood. In the present study, we examined the neural correlates of these difficulties. Groups of 16 currently euthymic, remitted depressed individuals and 16 healthy (control) women underwent functional magnetic resonance imaging (fMRI) during sad mood induction and during recovery from a sad mood state through recall of mood-incongruent positive autobiographical memories. Sad mood was induced in participants by using film clips; participants then recalled positive autobiographical memories, a procedure previously shown to repair negative affect. During both the sad mood induction and automatic mood regulation, control participants exhibited activation in the left ventrolateral prefrontal cortex (vlPFC) and cuneus; in contrast, remitted participants exhibited a decrease in activation in these regions. Furthermore, exploratory analyses revealed that reduced activation levels during mood regulation predicted a worsening of depressive symptoms at a 20-month follow-up assessment. These findings highlight a dynamic role of the vlPFC and cuneus in the experience and modulation of emotional states and suggest that functional anomalies of these brain regions are associated with a history of, and vulnerability to, depression.

  View details for DOI 10.3758/s13415-013-0216-0

  View details for Web of Science ID 000338516800026

  View details for PubMedCentralID PMC3995858

• Recalling happy memories in remitted depression: a neuroimaging investigation of the repair of sad mood. Cognitive, affective & behavioral neuroscience Foland-Ross, L. C., Cooney, R. E., Joormann, J., Henry, M. L., Gotlib, I. H. 2014; 14 (2): 818-826

  Abstract

  Major depressive disorder (MDD) is a recurrent mood disorder. The high rate of recurrence of MDD suggests the presence of stable vulnerability factors that place individuals with a history of major depression at an increased risk for the onset of another episode. Previous research has linked the remitted state, and therefore increased vulnerability for depressive relapse, with difficulties in the use of pleasant autobiographical memories to repair sad mood. In the present study, we examined the neural correlates of these difficulties. Groups of 16 currently euthymic, remitted depressed individuals and 16 healthy (control) women underwent functional magnetic resonance imaging (fMRI) during sad mood induction and during recovery from a sad mood state through recall of mood-incongruent positive autobiographical memories. Sad mood was induced in participants by using film clips; participants then recalled positive autobiographical memories, a procedure previously shown to repair negative affect. During both the sad mood induction and automatic mood regulation, control participants exhibited activation in the left ventrolateral prefrontal cortex (vlPFC) and cuneus; in contrast, remitted participants exhibited a decrease in activation in these regions. Furthermore, exploratory analyses revealed that reduced activation levels during mood regulation predicted a worsening of depressive symptoms at a 20-month follow-up assessment. These findings highlight a dynamic role of the vlPFC and cuneus in the experience and modulation of emotional states and suggest that functional anomalies of these brain regions are associated with a history of, and vulnerability to, depression.

  View details for DOI 10.3758/s13415-013-0216-0

  View details for PubMedID 24146315

• Neural Effects of Working Memory Training in Major Depressive Disorder: Facilitating Scientific Translation LeMoult, J., Foland-Ross, L. C., Sorenson, J., Ordaz, S. J., Bergman, S. R., Gotlib, I. H. ELSEVIER SCIENCE INC. 2014: 399S–400S

  View details for Web of Science ID 000334101802388

• Globus Pallidus Externa Projections to Frontal Cortex Sacchet, M. D., Chen, M. C., Fuller, P. M., Foland-Ross, L. C., Lu, J., Gotlib, I. H. ELSEVIER SCIENCE INC. 2014: 101S

  View details for Web of Science ID 000334101800312

• Automated Characterization of White Matter Connectivity in Major Depressive Disorder Sacchet, M. D., Prasad, G., Foland-Ross, L. C., Joshi, S. H., Hamilton, J., Thompson, P. M., Gotlib, I. H. ELSEVIER SCIENCE INC. 2014: 220S

  View details for Web of Science ID 000334101801259

• Support Vector Machines Can Identify Brain Network Anomalies in Major Depression Sacchet, M., Prasad, G., Foland-Ross, L. C., Thompson, P. M., Gotlib, I. H. ELSEVIER SCIENCE INC. 2014: 220S

  View details for Web of Science ID 000334101801260

• Differential Responses to Praise: Neural Markers of Risk for Depression Colich, N. L., Ordaz, S. J., Gotlib, I. H. ELSEVIER SCIENCE INC. 2014: 234S

  View details for Web of Science ID 000334101801303

• Neuroanatomical Predictors of the Onset of Major Depression in Adolescence Foland-Ross, L. C., Sacchet, M. D., Prasad, G., Gilbert, B., Thompson, P., Gotlib, I. ELSEVIER SCIENCE INC. 2014: 234S

  View details for Web of Science ID 000334101801304

• Brain Connectivity Classification of Major Depression with Enhanced Training Based on Alzheimer's Disease Datasets Prasad, G., Sacchet, M. D., Foland-Ross, L. C., Thompson, P. M., Gotlib, I. H. ELSEVIER SCIENCE INC. 2014: 234S–235S

  View details for Web of Science ID 000334101801305

• Increased Coupling of Default Network with Executive Network is Related to Rumination Jacobs, R. H., Gabriel, L. B., Jenkins, L. M., Ryan, K. A., Weisenbach, S. L., Baker, A., Peters, A. T., Barba, A., Varges, A., Ringrose, R., Harrington, G., Gotlib, I., Zubieta, J., Phan, K., Langenecker, S. A., Welsh, R. C. ELSEVIER SCIENCE INC. 2014: 240S

  View details for Web of Science ID 000334101801322

• An Integrative Investigation of Neural Function and Structure in Major Depression Foland-Ross, L. C., Gotlib, I. H. ELSEVIER SCIENCE INC. 2014: 364S

  View details for Web of Science ID 000334101802277

• CHARACTERIZING WHITE MATTER CONNECTIVITY IN MAJOR DEPRESSIVE DISORDER: AUTOMATED FIBER QUANTIFICATION AND MAXIMUM DENSITY PATHS. Proceedings. IEEE International Symposium on Biomedical Imaging Sacchet, M. D., Prasad, G., Foland-Ross, L. C., Joshi, S. H., Hamilton, J. P., Thompson, P. M., Gotlib, I. H. 2014; 11: 592-595

  Abstract

  Diffusion-weighted imaging allows for in vivo assessment of white matter structure, which can be used to assess aberrations associated with disease. Several new methods permit the automated assessment of important white matter characteristics. In the current study we used Automated Fiber Quantification (AFQ) to assess differences between depressed and nondepressed individuals in 18 major white matter tracts. We then used the Maximum Density Path (MDP) method to further characterize group differences identified with AFQ. The results of the AFQ analyses indicated that fractional anisotropy (FA; an index of white matter integrity) along bilateral corticospinal tracts (CST) was higher in depressed than in nondepressed individuals. MDP analyses revealed that white matter anomalies were restricted to four subregions that included the corona radiata and the internal and external capsules. These results provide further evidence that MDD is associated with abnormalities in cortical-to-subcortical connectivity.

  View details for PubMedID 25540677

• Children at risk for depression: Memory biases, self-schemas, and genotypic variation JOURNAL OF AFFECTIVE DISORDERS Asarnow, L. D., Thompson, R. J., Joormann, J., Gotlib, I. H. 2014; 159: 66-72

  Abstract

  Daughters of depressed mothers are at increased risk for developing a depressive disorder. We know relatively little, however, about the specific factors that contribute to this elevated risk. The present study investigated the effects of familial risk for depression and the 5-HTTLPR and COMT Val158Met polymorphisms, which have been associated with risk for depression, on biases in endorsement of and memory for positive and negative adjectives.Following a negative mood induction, 60 girls between the ages of 10 and 14 who had recurrent depressed mothers (high risk for depression) and 91 age-matched daughters of never-disordered mothers (low risk for depression) completed a Self-Referent Encoding Task in which they decided whether negative and positive adjectives described them. Following the task they were asked to recall as many of the adjectives as they could.Despite the absence of significant group differences in endorsement of positive or negative adjectives, high-risk girls with the COMT Val158Met Val/Val polymorphism recalled more positive (but not negative) words that they had endorsed than did high-risk girls who were homozygous for the Met allele. COMT was not associated with recall of valenced adjectives in low-risk girls. Across risk groups, 5-HTTLPR polymorphism was not associated with recall of valenced adjectives.Even with over 150 participants, there were relatively small numbers in some of the cells of this study, limiting its statistical power.These results suggest that assessing the interaction of familial risk status and COMT polymorphism is important in understanding the development of depressive disorders.

  View details for DOI 10.1016/j.jad.2014.02.020

  View details for Web of Science ID 000333398400011

  View details for PubMedID 24679392

  View details for PubMedCentralID PMC4000236

• ELUCIDATING BRAIN CONNECTIVITY NETWORKS IN MAJOR DEPRESSIVE DISORDER USING CLASSIFICATION-BASED SCORING. Proceedings. IEEE International Symposium on Biomedical Imaging Sacchet, M. D., Prasad, G., Foland-Ross, L. C., Thompson, P. M., Gotlib, I. H. 2014; 2014: 246-249

  Abstract

  Graph theory is increasingly used in the field of neuroscience to understand the large-scale network structure of the human brain. There is also considerable interest in applying machine learning techniques in clinical settings, for example, to make diagnoses or predict treatment outcomes. Here we used support-vector machines (SVMs), in conjunction with whole-brain tractography, to identify graph metrics that best differentiate individuals with Major Depressive Disorder (MDD) from nondepressed controls. To do this, we applied a novel feature-scoring procedure that incorporates iterative classifier performance to assess feature robustness. We found that small-worldness, a measure of the balance between global integration and local specialization, most reliably differentiated MDD from nondepressed individuals. Post-hoc regional analyses suggested that heightened connectivity of the subcallosal cingulate gyrus (SCG) in MDDs contributes to these differences. The current study provides a novel way to assess the robustness of classification features and reveals anomalies in large-scale neural networks in MDD.

  View details for PubMedID 25580184

• Can Memory Bias be Modified? The Effects of an Explicit Cued-Recall Training in Two Independent Samples COGNITIVE THERAPY AND RESEARCH Vrijsen, J. N., Becker, E. S., Rinck, M., van Oostrom, I., Speckens, A., Whitmer, A., Gotlib, I. H. 2014; 38 (2): 217-225

  View details for DOI 10.1007/s10608-013-9563-y

  View details for Web of Science ID 000332961200011

• DeCon: A tool to detect emotional concordance in multivariate time series data of emotional responding BIOLOGICAL PSYCHOLOGY Bulteel, K., Ceulemans, E., Thompson, R. J., Waugh, C. E., Gotlib, I. H., Tuerlinckx, F., Kuppens, P. 2014; 98: 29-42

  Abstract

  The occurrence of concordance among different response components during an emotional episode is a key feature of several contemporary accounts and definitions of emotion. Yet, capturing such response concordance in empirical data has proven to be elusive, in large part because of a lack of appropriate statistical tools that are tailored to measure the intricacies of response concordance in the context of data on emotional responding. In this article, we present a tool we developed to detect two different forms of response concordance-response patterning and synchronization-in multivariate time series data of emotional responding, and apply this tool to data concerning physiological responding to emotional stimuli. While the findings provide partial evidence for both response patterning and synchronization, they also show that the presence and nature of such patterning and synchronization is strongly person-dependent.

  View details for DOI 10.1016/j.biopsycho.2013.10.011

  View details for Web of Science ID 000335499900004

  View details for PubMedID 24220647

  View details for PubMedCentralID PMC4016122

• Activation of the medial prefrontal and posterior cingulate cortex during encoding of negative material predicts symptom worsening in major depression. Neuroreport Foland-Ross, L. C., Hamilton, P., Sacchet, M. D., Furman, D. J., Sherdell, L., Gotlib, I. H. 2014; 25 (5): 324-329

  Abstract

  Considerable research indicates that depressed individuals have better memory for negative material than do nondepressed individuals, and that this bias is associated with differential patterns of neural activation. It is not known, however, whether these aberrant activation patterns predict illness course. Using functional neuroimaging, we examined whether change in depressive symptoms is predicted by baseline patterns of neural activation that underlie negative memory biases in major depressive disorder. Depressed participants viewed negative and neutral pictures during functional MRI at baseline and completed an incidental memory task for these pictures 1 week later. Depression severity was assessed by administering the Beck Depression Inventory both at baseline (Time 1) and at Time 2, an average of 18 months later. Contrast maps of activation for subsequently remembered negative versus subsequently remembered neutral pictures were regressed against change in Beck Depression Inventory scores between Time 1 and Time 2, controlling for initial symptom severity. Results from this analysis revealed no associations between memory sensitivity for negative stimuli and symptom change. In contrast, whole brain analyses revealed significant positive associations between within-subject changes in depressive symptoms and baseline neural activation to successfully recalled negative pictures in the posterior cingulate cortex and medial prefrontal cortex. These findings indicate that neural activation in cortical midline regions is a better predictor of long-term symptomatic outcome than is memory sensitivity for negative material.

  View details for DOI 10.1097/WNR.0000000000000095

  View details for PubMedID 24356105

  View details for PubMedCentralID PMC3947655

• Increased insula coactivation with salience networks in insomnia. Biological psychology Chen, M. C., Chang, C., Glover, G. H., Gotlib, I. H. 2014; 97: 1-8

  Abstract

  Insomnia is among the most prevalent and costly of all sleep-related disorders. To characterize the neural mechanisms underlying subjective dysfunction in insomnia, we examined brain activity in 17 female insomniacs and 17 female healthy controls using simultaneous functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) while they were resting and while they were trying to fall asleep. In examining the dynamic regional activity within intrinsic brain networks, we found that, compared with controls, insomniacs had greater involvement of the anterior insula with salience networks, as well as insula BOLD correlation with EEG gamma frequency power during rest in insomniacs. This increased involvement of the anterior insula was associated with negative affect in insomniacs. Aberrant activation of the insula, which integrates temporal and bodily states, in arousal networks may underlie the misperception of sleep quality and subjective distress in insomnia.

  View details for DOI 10.1016/j.biopsycho.2013.12.016

  View details for PubMedID 24412227

• A profile approach to impulsivity in bipolar disorder: the key role of strong emotions. Acta psychiatrica Scandinavica Muhtadie, L., Johnson, S. L., Carver, C. S., Gotlib, I. H., Ketter, T. A. 2014; 129 (2): 100-108

  Abstract

  Bipolar disorder has been associated with elevated impulsivity - a complex construct subsuming multiple facets. We aimed to compare specific facets of impulsivity in bipolar disorder, including those related to key psychological correlates of the illness: reward sensitivity and strong emotion.Ninety-one individuals diagnosed with bipolar I disorder (inter-episode period) and 80 controls completed several well-validated impulsivity measures, including those relevant to reward (Fun-seeking subscale of the Behavioral Activation System scale) and emotion (Positive Urgency and Negative Urgency scales).Bipolar participants reported higher impulsivity scores than did controls on all of the impulsivity measures, except the Fun-seeking subscale of the Behavioral Activation System scale. Positive Urgency - a measure assessing the tendency to act impulsively when experiencing strong positive emotion - yielded the largest group differences: F(1,170) = 78.69, P < 0.001, partial η(2)  = 0.316. Positive Urgency was also associated with poorer psychosocial functioning in the bipolar group: ΔR(2)  = 0.24, b = -0.45, P < 0.001.Individuals with bipolar I disorder appear to be at particular risk of behaving impulsively when experiencing strong positive emotions. Findings provide an important first step toward developing a more refined understanding of impulsivity in bipolar disorder with the potential to inform targeted interventions.

  View details for DOI 10.1111/acps.12136

  View details for PubMedID 23600731

• Life stress and family history for depression: The moderating role of past depressive episodes JOURNAL OF PSYCHIATRIC RESEARCH Monroe, S. M., Slavich, G. M., Gotlib, I. H. 2014; 49: 90-95

  Abstract

  Three of the most consistently reported and powerful predictors of depression are a recent major life event, a positive family history for depression, and a personal history of past depressive episodes. Little research, however, has evaluated the inter-relations among these predictors in depressed samples. Such information is descriptively valuable and potentially etiologically informative. In the present article we summarize the existing literature and test four predictions in a sample of 62 clinically depressed individuals: (1) participants who experienced a major life event prior to onset would be less likely than participants who did not experience a major life event to have a positive family history for depression; (2) participants with a recent major life event would have fewer lifetime episodes of depression than would participants without; (3) participants with a positive family history for depression would have more lifetime episodes of depression than would participants with a negative family history for depression; and (4) we would obtain a 3-way interaction in which participants with a positive family history and without a major life event would have the most lifetime episodes, whereas participants with a negative family history and a major life event would have the fewest lifetime episodes. The first three predictions were confirmed, and the fourth prediction partially confirmed. These novel findings begin to elucidate the complex relations among these three prominent risk factors for depression, and point to avenues of research that may help illuminate the origins of depressive episodes.

  View details for DOI 10.1016/j.jpsychires.2013.11.005

  View details for Web of Science ID 000329772800013

  View details for PubMedID 24308926

  View details for PubMedCentralID PMC3918432

• Understanding Familial Risk for Depression: A 25-Year Perspective PERSPECTIVES ON PSYCHOLOGICAL SCIENCE Gotlib, I. H., Joormann, J., Foland-Ross, L. C. 2014; 9 (1): 94-108

  Abstract

  Major depressive disorder (MDD) is among the most prevalent, debilitating, and costly of all illnesses worldwide. Investigators have made considerable progress in elucidating psychological and biological correlates of MDD; however, far less is known about factors that are implicated in risk for depression. Given the high risk for MDD associated with a family history of depression, investigators have worked to understand both the effects of parental depression on offspring and the mechanisms that might underlie familial risk for MDD. In this article, we describe the evolution of investigators' understanding of the psychobiological functioning of children of depressed parents, and we present recent findings concerning cognitive and neural aspects of risk for MDD using our high-risk sample as a context and foundation for this discussion. We integrate these data in a conceptualization of mechanisms underlying risk for depression, focusing on the constructs of emotion dysregulation and stress reactivity. Recognizing the 25-year anniversary of the Association for Psychological Science, we place this presentation in the context of the past 25 years of research on depression. We conclude by discussing the significance of emotion dysregulation and stress reactivity for studying risk for depression, for developing approaches to prevent MDD, and for moving theory and research in this field forward.

  View details for DOI 10.1177/1745691613513469

  View details for Web of Science ID 000330848700013

• Differences Between Suicide Attempters and Nonattempters in Depressed Older Patients: Depression Severity, White-Matter Lesions, and Cognitive Functioning AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY Sachs-Ericsson, N., Hames, J. L., Joiner, T. E., Corsentino, E., Rushing, N. C., Palmer, E., Gotlib, I. H., Selby, E. A., Zarit, S., Steffens, D. C. 2014; 22 (1): 75–85

  Abstract

  The population of older adults with major depressive disorder (MDD) has the highest rate of suicide. White-matter brain lesions (WML) are a potential biologic marker for suicidality in young and middle-aged adults and are correlated with cognitive impairment in older adults. In this study of older patients with MDD, we examined 1) if a history of suicide attempts was associated with a more severe course of MDD; 2) if WML are a biologic marker for suicide; and 3) if suicide attempt history is associated with cognitive impairment mediated by WML.Data from the Neurocognitive Outcomes of Depression in the Elderly study.Depressed patients (60+) who had ever attempted suicide (n = 23) were compared with depressed patients (60+) who had not attempted suicide (n = 223).Baseline and follow-up assessments were obtained for depressive symptoms (every 3 months) and cognitive functioning (every 6 months) over 2 years. Three magnetic resonance imaging scans were conducted.At baseline, suicide attempters reported more severe past and present symptoms (e.g., depressive symptoms, current suicidal thoughts, psychotic symptoms, earlier age of onset, and more lifetime episodes) than nonattempters. Suicide attempters had more left WML at baseline, and suicide attempt history predicted a greater growth in both left and right WML. WML predicted cognitive decline; nonetheless, a history of suicide attempt was unrelated to cognitive functioning.Severity of depressive symptoms and WML are associated with suicide attempts in geriatric depressed patients. Suicide attempts predicted neurologic changes, which may contribute to poorer long-term outcomes in elder attempters.

  View details for DOI 10.1016/j.jagp.2013.01.063

  View details for Web of Science ID 000336050800009

  View details for PubMedID 23933424

  View details for PubMedCentralID PMC4155401

• Understanding Familial Risk for Depression: A 25-Year Perspective. Perspectives on psychological science Gotlib, I. H., Joormann, J., Foland-Ross, L. C. 2014; 9 (1): 94-108

  Abstract

  Major depressive disorder (MDD) is among the most prevalent, debilitating, and costly of all illnesses worldwide. Investigators have made considerable progress in elucidating psychological and biological correlates of MDD; however, far less is known about factors that are implicated in risk for depression. Given the high risk for MDD associated with a family history of depression, investigators have worked to understand both the effects of parental depression on offspring and the mechanisms that might underlie familial risk for MDD. In this article, we describe the evolution of investigators' understanding of the psychobiological functioning of children of depressed parents, and we present recent findings concerning cognitive and neural aspects of risk for MDD using our high-risk sample as a context and foundation for this discussion. We integrate these data in a conceptualization of mechanisms underlying risk for depression, focusing on the constructs of emotion dysregulation and stress reactivity. Recognizing the 25-year anniversary of the Association for Psychological Science, we place this presentation in the context of the past 25 years of research on depression. We conclude by discussing the significance of emotion dysregulation and stress reactivity for studying risk for depression, for developing approaches to prevent MDD, and for moving theory and research in this field forward.

  View details for DOI 10.1177/1745691613513469

  View details for PubMedID 26173248

• Memory for novel positive information in major depressive disorder. Cognition & emotion Sorenson, J. E., Furman, D. J., Gotlib, I. H. 2014; 28 (6): 1090-1099

  Abstract

  Major depressive disorder (MDD) is associated with biases in memory, including poor memory for positive stimuli. It is unclear, however, if this impaired memory for positive stimuli in MDD is related to difficulties in the initial processing of stimuli, or alternatively, reflects a decreased ability to draw on memories of positive stimuli after they have been formed. Using two versions of a word-matching task that featured a mixture of novel and practiced emotionally valenced words, we found that depressed individuals experienced greater difficulty learning positively valenced information than did their nondepressed peers. This difficulty seemed to be specific to initial encounters with the novel, but not the practiced, positive stimuli. These findings suggest that memory deficits for positive information associated with depression are related to how this information is initially processed. Implications of these findings for interventions are discussed and directions for future research are advanced.

  View details for DOI 10.1080/02699931.2013.866936

  View details for PubMedID 24382137

• Memory for novel positive information in major depressive disorder COGNITION & EMOTION Sorenson, J. E., Furman, D. J., Gotlib, I. H. 2014; 28 (6): 1090-1099

  Abstract

  Major depressive disorder (MDD) is associated with biases in memory, including poor memory for positive stimuli. It is unclear, however, if this impaired memory for positive stimuli in MDD is related to difficulties in the initial processing of stimuli, or alternatively, reflects a decreased ability to draw on memories of positive stimuli after they have been formed. Using two versions of a word-matching task that featured a mixture of novel and practiced emotionally valenced words, we found that depressed individuals experienced greater difficulty learning positively valenced information than did their nondepressed peers. This difficulty seemed to be specific to initial encounters with the novel, but not the practiced, positive stimuli. These findings suggest that memory deficits for positive information associated with depression are related to how this information is initially processed. Implications of these findings for interventions are discussed and directions for future research are advanced.

  View details for DOI 10.1080/02699931.2013.866936

  View details for Web of Science ID 000337979700009

  View details for PubMedCentralID PMC4065234

• Structural abnormality of the corticospinal tract in major depressive disorder. Biology of mood & anxiety disorders Sacchet, M. D., Prasad, G., Foland-Ross, L. C., Joshi, S. H., Hamilton, J. P., Thompson, P. M., Gotlib, I. H. 2014; 4: 8-?

  Abstract

  Scientists are beginning to document abnormalities in white matter connectivity in major depressive disorder (MDD). Recent developments in diffusion-weighted image analyses, including tractography clustering methods, may yield improved characterization of these white matter abnormalities in MDD. In this study, we acquired diffusion-weighted imaging data from MDD participants and matched healthy controls. We analyzed these data using two tractography clustering methods: automated fiber quantification (AFQ) and the maximum density path (MDP) procedure. We used AFQ to compare fractional anisotropy (FA; an index of water diffusion) in these two groups across major white matter tracts. Subsequently, we used the MDP procedure to compare FA differences in fiber paths related to the abnormalities in major fiber tracts that were identified using AFQ.FA was higher in the bilateral corticospinal tracts (CSTs) in MDD (p's < 0.002). Secondary analyses using the MDP procedure detected primarily increases in FA in the CST-related fiber paths of the bilateral posterior limbs of the internal capsule, right superior corona radiata, and the left external capsule.This is the first study to implicate the CST and several related fiber pathways in MDD. These findings suggest important new hypotheses regarding the role of CST abnormalities in MDD, including in relation to explicating CST-related abnormalities to depressive symptoms and RDoC domains and constructs.

  View details for DOI 10.1186/2045-5380-4-8

  View details for PubMedID 25295159

  View details for PubMedCentralID PMC4187017

• Anomalous gray matter structural networks in major depressive disorder. Biological psychiatry Singh, M. K., Kesler, S. R., Hadi Hosseini, S. M., Kelley, R. G., Amatya, D., Hamilton, J. P., Chen, M. C., Gotlib, I. H. 2013; 74 (10): 777-785

  Abstract

  BACKGROUND: Major depressive disorder (MDD) is characterized by abnormalities in structure, function, and connectivity in several brain regions. Few studies have examined how these regions are organized in the brain or investigated network-level structural aberrations that might be associated with depression. METHODS: We used graph analysis to examine the gray matter structural networks of individuals diagnosed with MDD (n = 93) and a demographically similar healthy comparison group (n = 151) with no history of psychopathology. The efficiency of structural networks for processing information was determined by quantifying local interconnectivity (clustering) and global integration (path length). We also compared the groups on the contributions of high-degree nodes (i.e., hubs) and regional network measures, including degree (number of connections in a node) and betweenness (fraction of short path connections in a node). RESULTS: Depressed participants had significantly decreased clustering in their brain networks across a range of network densities. Compared with control subjects, depressed participants had fewer hubs primarily in medial frontal and medial temporal areas, had higher degree in the left supramarginal gyrus and right gyrus rectus, and had higher betweenness in the right amygdala and left medial orbitofrontal gyrus. CONCLUSIONS: Networks of depressed individuals are characterized by a less efficient organization involving decreased regional connectivity compared with control subjects. Regional connections in the amygdala and medial prefrontal cortex may play a role in maintaining or adapting to depressive pathology. This is the first report of anomalous large-scale gray matter structural networks in MDD and provides new insights concerning the neurobiological mechanisms associated with this disorder.

  View details for DOI 10.1016/j.biopsych.2013.03.005

  View details for PubMedID 23601854

• Anomalous Gray Matter Structural Networks in Major Depressive Disorder BIOLOGICAL PSYCHIATRY Singh, M. K., Kesler, S. R., Hosseini, S. M., Kelley, R. G., Amatya, D., Hamilton, J. P., Chen, M. C., Gotlib, I. H. 2013; 74 (10): 777-785

  View details for DOI 10.1016/j.biopsych.2013.03.005

  View details for Web of Science ID 000325972700018

• Interoceptive awareness, positive affect, and decision making in Major Depressive Disorder JOURNAL OF AFFECTIVE DISORDERS Furman, D. J., Waugh, C. E., Bhattacharjee, K., Thompson, R. J., Gotlib, I. H. 2013; 151 (2): 780-785

  Abstract

  Little work has examined the relation between interoceptive awareness and symptoms of Major Depressive Disorder (MDD). Existing research suggests that depressed individuals exhibit impaired heartbeat perception, though the results of this research have been equivocal. Importantly, depressed participants in these studies have had comorbid anxiety disorders, making it difficult to draw inferences about interoceptive awareness in MDD. The current study addresses this issue by assessing heartbeat perception in depressed women without current anxiety disorders and exploring the relation between interoception and perturbations in both affective intensity and decision making, components of MDD postulated to be related to bodily awareness.Depressed women without concurrent anxiety disorders (n=25) and never-disordered controls (n=36) performed a heartbeat perception task. Participants completed the self-report Affect Intensity Measure (AIM), and decision-making difficulty was assessed in MDD participants using the Structured Clinical Interview for DSM-IV.Depressed women exhibited poorer heartbeat perception accuracy than did control participants. Impaired accuracy in MDD participants was associated with reduced positive affectivity and difficulty in decision making.Our sample was composed exclusively of females and was heterogeneous with respect to treatment status, thereby limiting our ability to generalize results to depressed males and to exclude the contribution of exogenous factors to the observed group differences.Results of this study suggest that for depressed individuals without anxiety comorbidities, disrupted perception of bodily responses reduces both the experience of positive arousal and the ability to use interoceptive feedback to inform decision making.

  View details for DOI 10.1016/j.jad.2013.06.044

  View details for Web of Science ID 000325432900052

  View details for PubMedID 23972662

  View details for PubMedCentralID PMC3797260

• Emotion Regulation in Depression and Anxiety: Examining Diagnostic Specificity and Stability of Strategy Use COGNITIVE THERAPY AND RESEARCH D'Avanzato, C., Joormann, J., Siemer, M., Gotlib, I. H. 2013; 37 (5): 968-980

  View details for DOI 10.1007/s10608-013-9537-0

  View details for Web of Science ID 000324817600010

• Using multiple methods to characterize the phenotype of individuals with a family history of major depressive disorder JOURNAL OF AFFECTIVE DISORDERS Watters, A. J., Gotlib, I. H., Harris, A. W., Boyce, P. M., Williams, L. M. 2013; 150 (2): 474-480

  Abstract

  Unaffected relatives (URs) of individuals with major depressive disorder (MDD) are biologically more vulnerable to depression. We compare healthy URs and controls at the level of phenotype (symptoms and functioning) and endophenotype (negative emotion bias), and further investigate the interrelation between these and the contribution of environmental early life stress.URs (n=101), identified using Family History Screen interview methods and matched controls completed written and interview questions assessing symptoms of depression and anxiety, negative cognitive style, life functioning and early life stress. Biases in emotion processing were measured using a facial expression of emotion identification paradigm.Compared to controls, URs reported higher levels of depression and anxiety, a stronger negative cognitive bias, and poorer functioning and lower satisfaction with life. URs were slower to correctly identify fear and sad facial expressions. A slower response time to identify sad faces was correlated with lower quality of life in the social domain. Early life stress (ELS) did not contribute significantly to any outcome.The methodology relies on accurate reporting of participants' own psychiatric history and that of their family members. The degree of vulnerability varies among URs.A family history of depression accounts for subtle differences in symptom levels and functioning without a necessary role of ELS. A negative emotion bias in processing emotion may be one vulnerability marker for MDD. Biological markers may affect functioning measures before symptoms at the level of experience.

  View details for DOI 10.1016/j.jad.2013.04.042

  View details for Web of Science ID 000323563300043

  View details for PubMedID 23764382

• Behavioral activation system moderates self-referent processing following recovery from depression PSYCHOLOGICAL MEDICINE Kircanski, K., Mazur, H., Gotlib, I. H. 2013; 43 (9): 1909-1919

  Abstract

  BACKGROUND: Previous research has implicated the behavioral activation system (BAS) in depression. The relationship of BAS functioning to aspects of cognitive vulnerability to depression, however, is not known. Method The present study investigated associations among level of BAS functioning and the encoding and recall of positive and negative self-referent information in currently non-depressed participants with a history of recurrent major depression (recovered; RMD) and in never-depressed control participants (CTL). Participants completed self-report measures of levels of BAS and behavioral inhibition system (BIS) functioning. Following a negative mood induction, participants were presented with a series of positive and negative adjectives; they indicated which words described them and later recalled as many of the words as they were able. RESULTS: The relationship of BAS functioning to self-referent processing was dependent on participant group. Although lower BAS reward responsivity was associated with the endorsement and recall of fewer positive words across groups, the magnitude of these associations was stronger, and was only significant, within the RMD group. Furthermore, only for RMD participants was lower BAS reward responsivity associated with the endorsement of more negative words. These effects were not accounted for by depressive or anxiety symptoms, current mood, or level of BIS functioning. CONCLUSIONS: These results indicate that BAS functioning may be distinctively linked to negatively biased self-referent processing, one facet of cognitive vulnerability to depression, in individuals with a history of major depressive disorder. Enhancing BAS functioning may be important in buffering cognitive vulnerability to depression.

  View details for DOI 10.1017/S0033291712002851

  View details for Web of Science ID 000322828600011

  View details for PubMedID 23298796

• HOLD ON TO THAT FEELING: THE NEURAL, EXPRESSIVE, AND BEHAVIORAL CORRELATES AND CONSEQUENCES OF AFFECTIVE MAINTENANCE Waugh, C. E., Lemus, M. G., Gotlib, I. H. WILEY-BLACKWELL. 2013: S135

  View details for Web of Science ID 000322995500749

• An Attentional Scope Model of Rumination PSYCHOLOGICAL BULLETIN Whitmer, A. J., Gotlib, I. H. 2013; 139 (5): 1036-1061

  Abstract

  Rumination, defined as repetitive thinking about negative information, has been found to lead to serious maladaptive consequences, including longer and more severe episodes of major depression. In this review, we present and discuss research findings motivated by the formulation that individual differences in cognitive processes that control how information is processed influence the likelihood that thoughts will become repetitive and negative. Several studies have demonstrated that a tendency to ruminate (i.e., trait rumination) is related to difficulties updating working memory (WM) and disengaging from and forgetting no-longer-relevant information. Other investigators have documented that trait rumination is also associated with an enhanced ability to ignore distracting information and with more stable maintenance of task-relevant information. In contrast to trait rumination, a state of rumination has been found to be related to widespread deficits in cognitive control. In this article, we discuss how the current accounts of control functioning cannot explain this pattern of anomalous control functioning. To explain these findings, including unexpected and contradictory results, we present an attentional scope model of rumination that posits that a constricted array of thoughts, percepts, and actions that are activated in WM or available for selection from long-term memory affects the control functioning of trait ruminators. This model explains, at a cognitive level, why rumination is particularly likely to arise when individuals are in a negative mood state; it also accounts for a number of findings outside of the rumination-control literature and generates several novel predictions.

  View details for DOI 10.1037/a0030923

  View details for Web of Science ID 000323688000008

  View details for PubMedID 23244316

  View details for PubMedCentralID PMC3773498

• The Effects of Neurofeedback Training of Salience Network Nodes on Affective Biases in Major Depression 68th Annual Scientific Meeting of the Society-of-Biological-Psychiatry Sacchet, M. D., Hamilton, J. P., Glover, G. H., Bagarinao, E., Chang, C., Mackey, S., Gotlib, I. H. ELSEVIER SCIENCE INC. 2013: 220S–220S

  View details for Web of Science ID 000318671800677

• Cortical Thinning in Children of Depressed Mothers Varies as a Function of Pubertal Status Foland-Ross, L. C., Gotlib, I. H. ELSEVIER SCIENCE INC. 2013: 135S

  View details for Web of Science ID 000318671800417

• People with bipolar I disorder report avoiding rewarding activities and dampening positive emotion JOURNAL OF AFFECTIVE DISORDERS Edge, M. D., Miller, C. J., Muhtadie, L., Johnson, S. L., Carver, C. S., Marquinez, N., Gotlib, I. H. 2013; 146 (3): 407-413

  Abstract

  Researchers have linked bipolar disorder to elevations in reward sensitivity and positive affect. Little is known, however, about how people with bipolar disorder respond to rewards and positive affect and how these tendencies relate to functioning or quality of life.Persons diagnosed with bipolar I disorder and matched controls completed the Responses to Positive Affect (RPA) measure and the Brief Quality of Life in Bipolar Disorder scale. Bipolar participants also completed the Reward Responses Inventory, which we designed to assess the extent to which participants avoid rewarding activities to prevent mania. A subsample of participants with bipolar disorder completed a positive mood induction procedure to examine the validity of the Response to Positive Affect scale.The majority of bipolar participants reported avoiding at least one rewarding activity as a means of preventing mania. In addition, people with bipolar I disorder reported more dampening responses to positive affect than did control participants. Dampening positive emotions was related to lower quality of life.This study does not address whether responses to affect and reward are related to the longitudinal course of symptoms.These findings suggest that people with bipolar I disorder seem to be aware of the potential of goal achievements to trigger mania, and many people with bipolar disorder seem to take steps to avoid positive emotion and reward.

  View details for DOI 10.1016/j.jad.2012.07.027

  View details for Web of Science ID 000315580700015

  View details for PubMedID 23021378

  View details for PubMedCentralID PMC3557770

• Neural systems approaches to understanding major depressive disorder: An intrinsic functional organization perspective NEUROBIOLOGY OF DISEASE Hamilton, J. P., Chen, M. C., Gotlib, I. H. 2013; 52: 4-11

  Abstract

  Recent research detailing the intrinsic functional organization of the brain provides a unique and useful framework to gain a better understanding of the neural bases of Major Depressive Disorder (MDD). In this review, we first present a brief history of neuroimaging research that has increased our understanding of the functional macro-architecture of the brain. From this macro-architectural perspective, we examine the extant body of functional neuroimaging research assessing MDD with a specific emphasis on the contributions of default-mode, executive, and salience networks in this debilitating disorder. Next, we describe recent investigations conducted in our laboratory in which we explicitly adopt a neural-system perspective in examining the relations among these networks in MDD. Finally, we offer directions for future research that we believe will facilitate the development of more detailed and integrative models of neural dysfunction in depression.

  View details for DOI 10.1016/j.nbd.2012.01.015

  View details for PubMedID 23477309

• The Neural Basis of Difficulties Disengaging From Negative Irrelevant Material in Major Depression PSYCHOLOGICAL SCIENCE Foland-Ross, L. C., Hamilton, J. P., Joormann, J., Berman, M. G., Jonides, J., Gotlib, I. H. 2013; 24 (3): 334-344

  Abstract

  Recurrent uncontrollable negative thoughts are a hallmark of depressive episodes. Deficits in cognitive control have been proposed to underlie this debilitating aspect of depression. Here, we used functional neuroimaging during an emotional working memory (WM) task to elucidate the neural correlates of these difficulties in cognitive control. In a WM manipulation involving depressed participants, the dorsal anterior cingulate and parietal and bilateral insular cortices were activated significantly more when negative words were removed from WM than when they were maintained in WM; in contrast, nondepressed participants exhibited stronger neural activations in these regions for positive than for negative material. These findings implicate anomalous activation of components of the task-positive network, known to be modulated by cognitive effort, in depression-associated difficulties in expelling negative material from WM. Future studies should examine the association between these aberrations and the maintenance of depressive symptoms.

  View details for DOI 10.1177/0956797612457380

  View details for Web of Science ID 000316640900014

  View details for PubMedID 23334445

• Acute Exercise Attenuates Negative Affect Following Repeated Sad Mood Inductions in Persons Who Have Recovered From Depression JOURNAL OF ABNORMAL PSYCHOLOGY Mata, J., Hogan, C. L., Joormann, J., Waugh, C. E., Gotlib, I. H. 2013; 122 (1): 45-50

  Abstract

  Identifying factors that may protect individuals from developing Major Depressive Disorder (MDD) in the face of stress is critical. In the current study we experimentally tested whether such a potentially protective factor, engaging in acute exercise, reduces the adverse effects of repeated sad mood inductions in individuals who have recovered from depression. We hypothesized that recovered depressed participants who engage in acute exercise report a smaller increase in negative affect (NA) and a smaller decrease in positive affect (PA) when exposed to a repeated sad mood induction (i.e., habituation), whereas participants who do not exercise show sensitization (i.e., increased NA and decreased PA in response to a repeated adverse stimulus). Forty-one women recovered from MDD and 40 healthy control women were randomly assigned to either exercise for 15 minutes or quiet rest. Afterward, participants were exposed to two sad mood inductions and reported their levels of affect throughout the study. Recovered depressed participants who had not exercised exhibited higher NA after the second sad mood induction, a finding consistent with sensitization. In contrast, both recovered depressed participants who had engaged in acute exercise and healthy control participants showed no increase in NA in response to the repeated sad mood induction. Participants who exercised reported higher PA after the exercise bout; however, our hypothesis concerning reported PA trajectories following the sad mood inductions was not supported. Results suggest that exercise can serve as a protective factor in the face of exposure to repeated emotional stressors, particularly concerning NA in individuals who have recovered from depression.

  View details for DOI 10.1037/a0029881

  View details for Web of Science ID 000314641500007

  View details for PubMedID 22985013

• Neurobiological markers of familial risk for depression. Current topics in behavioral neurosciences Foland-Ross, L. C., Hardin, M. G., Gotlib, I. H. 2013; 14: 181-206

  Abstract

  Major depression is associated with a wide range of neurobiological disturbances, including anomalies in the structure and function of cortical and subcortical gray matter and dysregulation of the HPA axis. In this chapter, we review research demonstrating that many of these abnormalities are also present in never-depressed offspring of adults with recurrent depression and discuss how such findings might reflect dysfunctional neuroregulatory systems that precede the onset of this disorder. We also briefly discuss candidate genes and environmental factors that have been posited to be directly involved in the transmission of neural and HPA-axis abnormalities from depressed parents to their offspring, and we review how, by obtaining a better understanding of the neurobiological markers of depression risk, we can facilitate the development of targeted strategies for the prevention and treatment of major depression.

  View details for DOI 10.1007/7854_2012_213

  View details for PubMedID 22573472

• A longitudinal study of differences in late- and early-onset geriatric depression: Depressive symptoms and psychosocial, cognitive, and neurological functioning AGING & MENTAL HEALTH Sachs-Ericsson, N., Corsentino, E., Moxley, J., Hames, J. L., Rushing, N. C., Sawyer, K., Joiner, T., Selby, E. A., Zarit, S., Gotlib, I. H., Steffens, D. C. 2013; 17 (1): 1-11

  Abstract

  Studies suggest early-onset depression (EOD) is associated with a more severe course of the depressive disorder, while late-onset depression (LOD) is associated with more cognitive and neuroimaging changes. This study examined if older adults with EOD, compared with those with LOD, would exhibit more severe symptoms of depression and, consistent with the glucocorticoid cascade hypothesis, have more hippocampal volume loss. A second goal was to determine if LOD, compared with EOD, would demonstrate more cognitive and neuroimaging changes.At regular intervals over a four-year period non-demented, older, depressed adults were assessed on the Mini-Mental Status Examination and the Montgomery-Asberg Depression Rating Scale. They were also assessed on magnetic resonance imaging.Compared with LOD, EOD had more depressive symptoms, more suicidal thoughts, and less social support. Growth curve analyses indicated that EOD demonstrated higher levels of residual depressive symptoms over time. The LOD group exhibited a greater decrement in cognitive scores. Contrary to the glucocorticoid cascade hypothesis, participants with EOD lost right hippocampal volume at a slower rate than did participants with LOD. Right cerebrum gray matter was initially smaller among participants with LOD.EOD is associated with greater severity of depressive illness. LOD is associated with more severe cognitive and neurological changes. These differences are relevant to understanding cognitive impairment in geriatric depression.

  View details for DOI 10.1080/13607863.2012.717253

  View details for Web of Science ID 000314396300001

  View details for PubMedID 22934752

• Dimensionality of brain networks linked to life-long individual differences in self-control NATURE COMMUNICATIONS Berman, M. G., Yourganov, G., Askren, M. K., Ayduk, O., Casey, B. J., Gotlib, I. H., Kross, E., McIntosh, A. R., Strother, S., Wilson, N. L., Zayas, V., Mischel, W., Shoda, Y., Jonides, J. 2013; 4

  Abstract

  The ability to delay gratification in childhood has been linked to positive outcomes in adolescence and adulthood. Here we examine a subsample of participants from a seminal longitudinal study of self-control throughout a subject's life span. Self-control, first studied in children at age 4 years, is now re-examined 40 years later, on a task that required control over the contents of working memory. We examine whether patterns of brain activation on this task can reliably distinguish participants with consistently low and high self-control abilities (low versus high delayers). We find that low delayers recruit significantly higher-dimensional neural networks when performing the task compared with high delayers. High delayers are also more homogeneous as a group in their neural patterns compared with low delayers. From these brain patterns, we can predict with 71% accuracy, whether a participant is a high or low delayer. The present results suggest that dimensionality of neural networks is a biological predictor of self-control abilities.

  View details for DOI 10.1038/ncomms2374

  View details for Web of Science ID 000316614600043

  View details for PubMedID 23340413

  View details for PubMedCentralID PMC3555568

• Reward Processing in Adolescents With Bipolar I Disorder JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY Singh, M. K., Chang, K. D., Kelley, R. G., Cui, X., Sherdell, L., Howe, M. E., Gotlib, I. H., Reiss, A. L. 2013; 52 (1): 68-83

  Abstract

  Bipolar disorder (BD) is a debilitating psychiatric condition that commonly begins in adolescence, a developmental period that has been associated with increased reward seeking. Because youth with BD are especially vulnerable to negative risk-taking behaviors, understanding the neural mechanisms by which dysregulated affect interacts with the neurobehavioral processing of reward is clearly important. One way to clarify how manic symptoms evolve in BD is to "prime" the affect before presenting rewarding stimuli. The objective of this study was to investigate the neural effects of an affective priming task designed to positively induce mood before reward processing in adolescents with and without BD.Neural activity and behaviors during the anticipation of and response to monetary reward and loss after an affective prime were compared using functional magnetic resonance imaging in 13- to 18-year-old adolescents with a recent onset of BD-I (n = 24) and demographically matched healthy comparison youth (n = 24).Compared with the healthy control youth, youth with BD had speeded reaction times and showed decreased activation in the thalamus and inferior temporal gyrus while anticipating gains after priming but increased activations in the middle frontal gyrus and parietal cortices while anticipating losses after priming. Youth with BD also showed less activation in the inferior parietal lobule, thalamus, and superior frontal gyrus while receiving losses after priming.Aberrant prefrontal and subcortical activations during reward processing suggest mechanisms that may underlie disordered self-awareness during goal pursuit and motivation in BD. Longitudinal studies are needed to examine whether this pattern of neural activation predicts a poorer long-term outcome.

  View details for DOI 10.1016/j.jaac.2012.10.004

  View details for PubMedID 23265635

• The role of attention to emotion in recovery from major depressive disorder. Depression research and treatment Thompson, R. J., Mata, J., Jaeggi, S. M., Buschkuehl, M., Jonides, J., Gotlib, I. H. 2013; 2013: 540726-?

  Abstract

  Major Depressive Disorder (MDD) is characterized by several emotional disturbances. One possible but not well-examined disturbance is in attention to emotion, an important facet of emotional awareness. We examined whether attention to emotion predicted recovery from MDD. Fifty-three adults with current MDD completed a week of experience sampling (Time 1). At each prompt, participants reported attention to emotion, negative affect (NA), and positive affect (PA). Approximately one year later (Time 2), the depressive status of 27 participants was reassessed. Participants who had recovered from MDD (n = 8) indicated paying less attention to their emotions at Time 1 than did participants who had not fully recovered (n = 19). Attention to emotion was better predictor of recovery than was severity of MDD, NA, or PA at Time 1. Levels of attention to emotion at Time 1 in participants who recovered from MDD did not differ significantly from the levels reported by 53 never-depressed individuals who had participated in the experience sampling. Findings indicate that high levels of an otherwise adaptive emotional facet can adversely affect the course of MDD.

  View details for DOI 10.1155/2013/540726

  View details for PubMedID 23853719

  View details for PubMedCentralID PMC3703346

• Depressive rumination and the C957T polymorphism of the DRD2 gene COGNITIVE AFFECTIVE & BEHAVIORAL NEUROSCIENCE Whitmer, A. J., Gotlib, I. H. 2012; 12 (4): 741-747

  Abstract

  Depressed individuals who ruminate have difficulties learning from punishment and suppressing task-irrelevant information. The C957T polymorphism of the DRD2 gene, which affects functioning of D2 dopamine receptors (DRD2) that are expressed predominantly in the indirect pathway of the basal ganglia, has been found to influence suppression and punishment learning. Given these associations, we examined in the present study whether depressive rumination is related to the C957T polymorphism in 317 clinically depressed individuals and 317 never-depressed control individuals. A 2 × 2 (diagnostic group ×C957T polymorphism) analysis of variance conducted on depressive rumination scores yielded a significant interaction of group and C957T: Individuals with two 957C alleles reported higher levels of depressive rumination than did individuals with one or two 957T alleles if they were depressed, but not if they were healthy. The present findings suggest that the dopaminergic system and DRD2 are related to the frequency of maladaptive rumination in depressed individuals. Thus, DRD2 may be an important target for the pharmacological treatment of depressive rumination.

  View details for DOI 10.3758/s13415-012-0112-z

  View details for Web of Science ID 000311498900010

  View details for PubMedID 22864973

• The Everyday Emotional Experience of Adults With Major Depressive Disorder: Examining Emotional Instability, Inertia, and Reactivity JOURNAL OF ABNORMAL PSYCHOLOGY Thompson, R. J., Mata, J., Jaeggi, S. M., Buschkuehl, M., Jonides, J., Gotlib, I. H. 2012; 121 (4): 819-829

  Abstract

  Investigators have begun to examine the temporal dynamics of affect in individuals diagnosed with major depressive disorder (MDD), focusing on instability, inertia, and reactivity of emotion. How these dynamics differ between individuals with MDD and healthy controls have not before been examined in a single study. In this study, 53 adults with MDD and 53 healthy adults carried hand-held electronic devices for approximately 7 days and were prompted randomly 8 times per day to report their levels of current negative affect (NA), positive affect (PA), and the occurrence of significant events. In terms of NA, compared with healthy controls, depressed participants reported greater instability and greater reactivity to positive events, but comparable levels of inertia and reactivity to negative events. Neither average levels of NA nor NA reactivity to, frequency or intensity of, events accounted for the group difference in instability of NA. In terms of PA, the MDD and control groups did not differ significantly in their instability, inertia, or reactivity to positive or negative events. These findings highlight the importance of emotional instability in MDD, particularly with respect to NA, and contribute to a more nuanced understanding of the everyday emotional experiences of depressed individuals.

  View details for DOI 10.1037/a0027978

  View details for Web of Science ID 000311527700003

  View details for PubMedID 22708886

  View details for PubMedCentralID PMC3624976

• Interacting with nature improves cognition and affect for individuals with depression JOURNAL OF AFFECTIVE DISORDERS Berman, M. G., Kross, E., Krpan, K. M., Askren, M. K., Burson, A., Deldin, P. J., Kaplan, S., Sherdell, L., Gotlib, I. H., Jonides, J. 2012; 140 (3): 300-305

  Abstract

  This study aimed to explore whether walking in nature may be beneficial for individuals with major depressive disorder (MDD). Healthy adults demonstrate significant cognitive gains after nature walks, but it was unclear whether those same benefits would be achieved in a depressed sample as walking alone in nature might induce rumination, thereby worsening memory and mood.Twenty individuals diagnosed with MDD participated in this study. At baseline, mood and short term memory span were assessed using the PANAS and the backwards digit span (BDS) task, respectively. Participants were then asked to think about an unresolved negative autobiographical event to prime rumination, prior to taking a 50-min walk in either a natural or urban setting. After the walk, mood and short-term memory span were reassessed. The following week, participants returned to the lab and repeated the entire procedure, but walked in the location not visited in the first session (i.e., a counterbalanced within-subjects design).Participants exhibited significant increases in memory span after the nature walk relative to the urban walk, p<.001, η(p)(2)=.53 (a large effect-size). Participants also showed increases in mood, but the mood effects did not correlate with the memory effects, suggesting separable mechanisms and replicating previous work.Sample size and participants' motivation.These findings extend earlier work demonstrating the cognitive and affective benefits of interacting with nature to individuals with MDD. Therefore, interacting with nature may be useful clinically as a supplement to existing treatments for MDD.

  View details for DOI 10.1016/j.jad.2012.03.012

  View details for Web of Science ID 000307434200013

  View details for PubMedID 22464936

  View details for PubMedCentralID PMC3393816

• Feeling Blue or Turquoise? Emotional Differentiation in Major Depressive Disorder PSYCHOLOGICAL SCIENCE Demiralp, E., Thompson, R. J., Mata, J., Jaeggi, S. M., Buschkuehl, M., Barrett, L. F., Ellsworth, P. C., Demiralp, M., Hernandez-Garcia, L., Deldin, P. J., Gotlib, I. H., Jonides, J. 2012; 23 (11): 1410-1416

  Abstract

  Some individuals have very specific and differentiated emotional experiences, such as anger, shame, excitement, and happiness, whereas others have more general affective experiences of pleasure or discomfort that are not as highly differentiated. Considering that individuals with major depressive disorder (MDD) have cognitive deficits for negative information, we predicted that people with MDD would have less differentiated negative emotional experiences than would healthy people. To test this hypothesis, we assessed participants' emotional experiences using a 7-day experience-sampling protocol. Depression was assessed using structured clinical interviews and the Beck Depression Inventory-II. As predicted, individuals with MDD had less differentiated emotional experiences than did healthy participants, but only for negative emotions. These differences were above and beyond the effects of emotional intensity and variability.

  View details for DOI 10.1177/0956797612444903

  View details for Web of Science ID 000314501400018

  View details for PubMedID 23070307

• Volumetric reductions in the subgenual anterior cingulate cortex in adolescents with bipolar I disorder BIPOLAR DISORDERS Singh, M. K., Chang, K. D., Chen, M. C., Kelley, R. G., Garrett, A., Mitsunaga, M. M., Bararpour, L., Howe, M., Reiss, A. L., Gotlib, I. H. 2012; 14 (6): 585-596

  Abstract

  A range of prefrontal and subcortical volumetric abnormalities have been found in adults and adolescents with bipolar disorder. It is unclear, however, if these deficits are present early in the onset of mania or are a consequence of multiple mood episodes or prolonged exposure to medication. The goal of this study was to examine whether youth with bipolar I disorder who recently experienced their first episode of mania are characterized by brain volumetric abnormalities.Anatomical images from magnetic resonance imaging of 26 13- to 18-year-old adolescents with bipolar I disorder and 24 age-comparable healthy controls with no personal or family history of psychopathology were analyzed using whole-brain voxel-based morphometry (VBM).Compared with healthy controls, adolescents with bipolar I disorder had significantly less gray matter volume in the left subgenual cingulate cortex [p<0.05, family-wise error (FWE)-corrected].Adolescents with a recent single episode of mania have smaller subgenual cingulate cortex volume than do their healthy counterparts, suggesting that this anomaly occurs early in the onset of, or may predate the disorder. Longitudinal studies are needed to examine the impact of this volumetric reduction on the course and outcome of this disorder.

  View details for DOI 10.1111/j.1399-5618.2012.01043.x

  View details for PubMedID 22938166

• Information processing in adolescents with bipolar I disorder JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY Whitney, J., Joormann, J., Gotlib, I. H., Kelley, R. G., Acquaye, T., Howe, M., Chang, K. D., Singh, M. K. 2012; 53 (9): 937-945

  Abstract

  Cognitive models of bipolar I disorder (BD) may aid in identification of children who are especially vulnerable to chronic mood dysregulation. Information-processing biases related to memory and attention likely play a role in the development and persistence of BD among adolescents; however, these biases have not been extensively studied in youth with BD.We administered the self-referent encoding task and the dot-probe task to adolescents with bipolar I disorder (BD, n = 35) and a demographically similar healthy comparison group (HC, n = 25) at baseline, and at a 1-year follow-up in a subset of this cohort (n = 22 per group).At both baseline and 1-year follow-up, there were significant interactions of group (BD, HC) and valence of stimulus (positive, negative adjective) on endorsement and recall of self-referent adjectives. HC adolescents endorsed and recalled more positive self-referent adjectives at baseline and follow-up while adolescents with BD endorsed and recalled more negative self-referent adjectives at baseline but not follow-up. Over time, depression symptomatology was associated with impaired memory for positive self-referent adjectives. There were no group differences in attentional bias at either time points.Adolescents with BD exhibit bias away from endorsement and recall of positive adjectives, which remained stable over time and independent of mood state.

  View details for DOI 10.1111/j.1469-7610.2012.02543.x

  View details for PubMedID 22390273

• PUBERTAL STAGE AND BRAIN ANATOMY IN GIRLS NEUROSCIENCE Blanton, R. E., Cooney, R. E., Joormann, J., Eugene, F., Glover, G. H., Gotlib, I. H. 2012; 217: 105-112

  Abstract

  Studies of puberty have focused primarily on changes in hormones and on observable physical bodily characteristics. Little is known, however, about the nature of the relation between pubertal status and brain physiology. This is particularly important given findings that have linked the onset of puberty with both changes in cognitive functioning and increases in the incidence of depression and anxiety. The present study examined relations between pubertal stage, as assessed by Tanner staging, and brain anatomy in a sample of 54 girls aged 9-15 years. Brain morphometric analysis was conducted using high-resolution magnetic resonance imaging (MRI). The hippocampus and amygdala were manually traced on MRI scans in all participants. Stepwise regression analyses were conducted with total intracranial volume (ICV), age, and pubertal status as the predictor variables and hippocampus and amygdala volumes as outcome variables. Pubertal status was significantly associated with left amygdala volume, after controlling for both age and ICV. In addition, puberty was related to right hippocampus and amygdala volumes, after controlling for ICV. In contrast, no significant associations were found between age and hippocampal and amygdala volumes after controlling for pubertal status and ICV. These findings highlight the importance of the relation between pubertal status and morphometry of the hippocampus and amygdala, and of limbic and subcortical structures that have been implicated in emotional and social behaviors.

  View details for DOI 10.1016/j.neuroscience.2012.04.059

  View details for Web of Science ID 000306156000011

  View details for PubMedID 22569152

• Switching and Backward Inhibition in Major Depressive Disorder: The Role of Rumination JOURNAL OF ABNORMAL PSYCHOLOGY Whitmer, A. J., Gotlib, I. H. 2012; 121 (3): 570-578

  Abstract

  Previous studies have demonstrated that individuals with major depressive disorder have difficulties switching attention from one task set to another. In the current study we examined whether ruminative thinking drives the switching deficits of depressed individuals. A secondary, more exploratory, goal of this study was to examine whether state rumination would impair depressed individuals' ability to activate a new task set, to inhibit a no longer relevant task set, or both. Participants underwent either a rumination induction or a distraction induction and then completed a backward inhibition task that measures general switching abilities and the ability to inhibit previous task sets. Although depression was not related to switching ability as a main effect, depressed individuals who were induced to ruminate exhibited poorer switching ability than did both depressed and control individuals who were distracted from ruminating and control participants who were induced to ruminate. These findings suggest that depressed individuals are characterized by switching deficits only if they are ruminating. Moreover, the finding that state rumination did not affect participants' ability to inhibit previous task sets suggests that state rumination primarily impairs noninhibitory task-switching processes. It is interesting that the opposite pattern of results was obtained for trait rumination, which was related to inhibitory deficits during switching, but not to generally poorer switching. Thus, state and trait rumination may be associated with dissociable cognitive deficits.

  View details for DOI 10.1037/a0027474

  View details for Web of Science ID 000307482700003

  View details for PubMedID 22468767

• Elevated Ambitions for Fame Among Persons Diagnosed With Bipolar I Disorder JOURNAL OF ABNORMAL PSYCHOLOGY Johnson, S. L., Carver, C. S., Gotlib, I. H. 2012; 121 (3): 602-609

  Abstract

  A growing body of evidence suggests that people with bipolar disorder are highly goal-oriented. Compared to other persons, they expend more effort to attain rewards and view goal pursuit as more important to their self-worth. Persons at risk for mania and those diagnosed with bipolar spectrum disorders have been shown to endorse highly ambitious life goals, such as becoming a multimillionaire or achieving fame. This study is the first examination of whether such elevated goals characterize persons diagnosed with bipolar I disorder. We also examined whether elevated ambitions predicted symptom change over time. Ninety-two persons with bipolar I disorder and 81 age- and sex-matched controls completed the Willingly Approached Set of Statistically Unlikely Pursuits, a measure of extremely high life ambitions. A subset of the bipolar participants completed a 3-month follow-up interview. Participants with bipolar disorder endorsed higher ambitions for popular fame than did controls; moreover, heightened ambitions for popular fame and financial success predicted increases in manic symptoms in those with bipolar disorder over the next three months. Discussion focuses on goal regulation in bipolar disorder.

  View details for DOI 10.1037/a0026370

  View details for Web of Science ID 000307482700006

  View details for PubMedID 22103804

• Automaticity in anxiety disorders and major depressive disorder CLINICAL PSYCHOLOGY REVIEW Teachman, B. A., Joormann, J., Steinman, S. A., Gotlib, I. H. 2012; 32 (6): 575-603

  Abstract

  In this paper we examine the nature of automatic cognitive processing in anxiety disorders and Major Depressive Disorder (MDD). Rather than viewing automaticity as a unitary construct, we follow a social cognition perspective (Bargh, 1994) that argues for four theoretically independent features of automaticity: unconscious (processing of emotional stimuli occurs outside awareness), efficient (processing emotional meaning uses minimal attentional resources), unintentional (no goal is needed to engage in processing emotional meaning), and uncontrollable (limited ability to avoid, alter or terminate processing emotional stimuli). Our review of the literature suggests that most anxiety disorders are characterized by uncontrollable, and likely also unconscious and unintentional, biased processing of threat-relevant information. In contrast, MDD is most clearly typified by uncontrollable, but not unconscious or unintentional, processing of negative information. For the anxiety disorders and for MDD, there is no sufficient evidence to draw firm conclusions about efficiency of processing, though early indications are that neither anxiety disorders nor MDD are characterized by this feature. Clinical and theoretical implications of these findings are discussed and directions for future research are offered. In particular, it is clear that paradigms that more directly delineate the different features of automaticity are required to gain a more comprehensive and systematic understanding of the importance of automatic processing in emotion dysregulation.

  View details for DOI 10.1016/j.cpr.2012.06.004

  View details for Web of Science ID 000308049600013

  View details for PubMedID 22858684

  View details for PubMedCentralID PMC3419810

• Functional Neuroimaging of Major Depressive Disorder: A Meta-Analysis and New Integration of Baseline Activation and Neural Response Data AMERICAN JOURNAL OF PSYCHIATRY Hamilton, J. P., Etkin, A., Furman, D. J., Lemus, M. G., Johnson, R. F., Gotlib, I. H. 2012; 169 (7): 693-703

  Abstract

  Functional neuroimaging investigations of major depressive disorder can advance both the neural theory and treatment of this debilitating illness. Inconsistency of neuroimaging findings and the use of region-of-interest approaches have hindered the development of a comprehensive, empirically informed neural model of major depression. In this context, the authors sought to identify reliable anomalies in baseline neural activity and neural response to affective stimuli in major depressive disorder.The authors applied voxel-wise, whole-brain meta-analysis to neuroimaging investigations comparing depressed to healthy comparison groups with respect to baseline neural activity or neural response to positively and/or negatively valenced stimuli.Relative to healthy subjects, those with major depression had reliably higher baseline activity, bilaterally, in the pulvinar nucleus. The analysis of neural response studies using negative stimuli showed greater response in the amygdala, insula, and dorsal anterior cingulate cortex and lower response in the dorsal striatum and dorsolateral prefrontal cortex in individuals with major depressive disorder than in healthy subjects.The meta-analytic results support an elegant and neuroanatomically viable model of the salience of negative information in major depressive disorder. In this proposed model, high baseline pulvinar activity in depression first potentiates responding of the brain's salience network to negative information; next, and owing potentially to low striatal dopamine levels in depression, this viscerally charged information fails to propagate up the cortical-striatal-pallidalthalamic circuit to the dorsolateral prefrontal cortex for contextual processing and reappraisal.

  View details for DOI 10.1176/appi.ajp.2012.11071105

  View details for Web of Science ID 000305853400007

  View details for PubMedID 22535198

• Cognitive aspects of depression WILEY INTERDISCIPLINARY REVIEWS-COGNITIVE SCIENCE Kircanski, K., Joormann, J., Gotlib, I. H. 2012; 3 (3): 301-313

  Abstract

  Depression is a prevalent and impairing psychiatric disorder that affects how we feel and how we think about ourselves and the world around us. Cognitive theories of depression have long posited that various thought processes are involved in the development, maintenance, and recurrence of depressive episodes. Contemporary research has utilized experimental procedures to examine cognitive processes in depressed individuals as well as the nature of the relation of these processes to the emotion dysregulation that is central to the disorder. For example, investigators have assessed the ways in which depression alters aspects of information processing, including attention and perception, interpretation, and memory processes; this research has generated relatively consistent findings. In addition, researchers have attempted to identify and elucidate the cognitive mechanisms that may link these biases in information processing to emotion dysregulation in depression. These mechanisms include inhibitory processes and deficits in working memory, ruminative responses to negative mood states, and the inability to use positive and rewarding stimuli to regulate negative mood. Results of these investigations converge on the formulation that depression is associated with increased elaboration of negative information, difficulties in cognitive control when processing this information, and difficulties disengaging from this information. Research examining cognitive aspects of depression not only enhances our understanding of this common and costly disorder, but also has implications for the treatment of depression and for future investigations of the biological foundations of this disorder.

  View details for DOI 10.1002/wcs.1177

  View details for Web of Science ID 000302867000003

  View details for PubMedCentralID PMC3518852

• Walk on the Bright Side: Physical Activity and Affect in Major Depressive Disorder JOURNAL OF ABNORMAL PSYCHOLOGY Mata, J., Thompson, R. J., Jaeggi, S. M., Buschkuehl, M., Jonides, J., Gotlib, I. H. 2012; 121 (2): 297-308

  Abstract

  Although prescribed exercise has been found to improve affect and reduce levels of depression, we do not know how self-initiated everyday physical activity influences levels of positive affect (PA) and negative affect (NA) in depressed persons. Fifty-three individuals diagnosed with Major Depressive Disorder (MDD) and 53 never-depressed controls participated in a seven-day experience sampling study. Participants were prompted randomly eight times per day and answered questions about their physical activity and affective state. Over the week, the two groups of participants did not differ in average level of physical activity. As expected, participants with MDD reported lower average PA and higher average NA than did never-depressed controls. Both participants with MDD and controls reported higher levels of PA at prompts after physical activity than at prompts after inactive periods; moreover, for both groups of participants, PA increased from a prompt after an inactive period to a subsequent prompt at which activity was reported. Depressed participants in particular showed a dose-response effect of physical activity on affect: longer duration and/or higher intensity of physical activity increased their PA significantly more than did short duration and/or lower intensity physical activity. Physical activity did not influence NA in either group. In contrast to previous treatment studies that examined the effects of prescribed structured exercise, this investigation showed that self-initiated physical activity influences PA. These findings also underscore the importance of distinguishing between PA and NA to gain a more comprehensive understanding of the effects of physical activity on affect in MDD.

  View details for DOI 10.1037/a0023533

  View details for Web of Science ID 000304131400001

  View details for PubMedID 21553939

• Affective and physiological responses to stress in girls at elevated risk for depression DEVELOPMENT AND PSYCHOPATHOLOGY Waugh, C. E., Muhtadie, L., Thompson, R. J., Joormann, J., Gotlib, I. H. 2012; 24 (2): 661-675

  Abstract

  Children of depressed parents are significantly more likely to develop depression and other mental health disorders than are children of never-depressed parents. Investigations of the physiological mechanisms underlying this elevated risk have generally focused on basal functioning. It is important to note, however, that physiological reactivity or responses to stress are also critical determinants of mental and physical health. In the current study, we examined whether children of depressed parents exhibit altered physiological responses to stress. In two studies, never-depressed adolescent daughters of either recurrently depressed mothers (RISK) or never-depressed mothers (CTL) underwent social stressors while their physiological responses were measured (cortisol in Study 1, heart rate in Study 2). In both studies, affective responses to the stressors predicted physiological responses in RISK girls, but not in never-depressed girls. For RISK girls, decreased positive affect in response to stress predicted increased cortisol reactivity; in addition, decreased positive affect and increased negative affect were associated with poorer heart rate recovery and habituation, respectively. Future research is needed to examine explicitly whether this coherence between affect and physiology is a mechanism underlying the increased risk for psychopathology in children of depressed parents.

  View details for DOI 10.1017/S0954579412000235

  View details for Web of Science ID 000302915900023

  View details for PubMedID 22559138

• Depressive Rumination and the NoGo Pathway of the Basal Ganglia: A Genetic Study 67th Annual Meeting of the Society-of-Biological-Psychiatry Whitmer, A. J., Gotlib, I. H. ELSEVIER SCIENCE INC. 2012: 156S–157S

  View details for Web of Science ID 000302466000492

• Evidence of Abnormal Cortical Gray Matter Development in Never-Depressed Daughters of Mothers with Recurrent Depression Foland-Ross, L. C., Gilbert, B. L., Raman, M., Burley, H., Reiss, A. L., Gotlib, I. H. ELSEVIER SCIENCE INC. 2012: 204S

  View details for Web of Science ID 000302466000635

• Resting State Functional Connectivity in Healthy Offspring of Parents with Bipolar Disorder Singh, M. K., Kelley, R. G., Shoemaker, V. R., Li, S., Boucher, S., Gotlib, I. H., Reiss, A. L., Chang, K. D. ELSEVIER SCIENCE INC. 2012: 204S–205S

  View details for Web of Science ID 000302466000636

• Cognitive and Neural Predictors of First-Onset MDD in Young High-Risk Girls Gotlib, I. H. ELSEVIER SCIENCE INC. 2012: 20S

  View details for Web of Science ID 000302466000065

• Activations in Posterior Cingulate Cortex and Subcallosal Gyrus During Affective Encoding Predict Change in Symptomatology in Major Depressive Disorder 67th Annual Meeting of the Society-of-Biological-Psychiatry Sacchet, M., Foland-Ross, L. C., Hamilton, J. P., Sherdell, L., Gotlib, I. H. ELSEVIER SCIENCE INC. 2012: 79S–79S

  View details for Web of Science ID 000302466000250

• Altered Small-World Properties of Gray Matter Networks in Major Depression 67th Annual Meeting of the Society-of-Biological-Psychiatry Singh, M. K., Kesler, S. R., Hosseini, H., Kelley, R. G., Amatya, D., Hamilton, P., Chen, M. C., Gotlib, I. H. ELSEVIER SCIENCE INC. 2012: 106S–106S

  View details for Web of Science ID 000302466000336

• Anomalous functional brain activation following negative mood induction in children with pre-school onset major depression DEVELOPMENTAL COGNITIVE NEUROSCIENCE Pagliaccio, D., Luby, J., Gaffrey, M., Belden, A., Botteron, K., Gotlib, I. H., Barch, D. M. 2012; 2 (2): 256-267

  Abstract

  While major depressive disorder has been shown to be a significant mental health issue for school-age children, recent research indicates that depression can be observed in children as early as the preschool period. Yet, little work has been done to explore the neurobiological factors associated with this early form of depression. Given research suggesting a relation between adult depression and anomalies in emotion-related neural circuitry, the goal of the current study was to elucidate changes in functional activation during negative mood induction and emotion regulation in school-age children with a history of preschool-onset depression. The results suggest that a history of depression during the preschool period is associated with decreased activity in prefrontal cortex during mood induction and regulation. Moreover, the severity of current depressed mood was associated with increased activity in limbic regions, such as the amygdala, particularly in children with a history of depression. Similar to results observed in adult depression, the current findings indicate disruptions in emotion-related neural circuitry associated with preschool-onset depression.

  View details for DOI 10.1016/j.dcn.2011.11.008

  View details for Web of Science ID 000315317600006

  View details for PubMedID 22483075

  View details for PubMedCentralID PMC3322366

• Cognitive Aspects of Depression. Wiley interdisciplinary reviews. Cognitive science Kircanski, K., Joormann, J., Gotlib, I. H. 2012; 3 (3): 301-313

  Abstract

  Depression is a prevalent and impairing psychiatric disorder that affects how we feel and how we think about ourselves and the world around us. Cognitive theories of depression have long posited that various thought processes are involved in the development, maintenance, and recurrence of depressive episodes. Contemporary research has utilized experimental procedures to examine cognitive processes in depressed individuals as well as the nature of the relation of these processes to the emotion dysregulation that is central to the disorder. For example, investigators have assessed the ways in which depression alters aspects of information processing, including attention and perception, interpretation, and memory processes; this research has generated relatively consistent findings. In addition, researchers have attempted to identify and elucidate the cognitive mechanisms that may link these biases in information processing to emotion dysregulation in depression. These mechanisms include inhibitory processes and deficits in working memory, ruminative responses to negative mood states, and the inability to use positive and rewarding stimuli to regulate negative mood. Results of these investigations converge on the formulation that depression is associated with increased elaboration of negative information, difficulties in cognitive control when processing this information, and difficulties disengaging from this information. Research examining cognitive aspects of depression not only enhances our understanding of this common and costly disorder, but also has implications for the treatment of depression and for future investigations of the biological foundations of this disorder.

  View details for PubMedID 23240069

  View details for PubMedCentralID PMC3518852

• Neural Correlates of Automatic Mood Regulation in Girls at High Risk for Depression JOURNAL OF ABNORMAL PSYCHOLOGY Joormann, J., Cooney, R. E., Henry, M. L., Gotlib, I. H. 2012; 121 (1): 61-72

  Abstract

  Daughters of depressed mothers are at significantly elevated risk for developing a depressive disorder themselves. We have little understanding, however, of the specific factors that contribute to this risk. The ability to regulate negative affect effectively is critical to emotional and physical health and may play an important role in influencing risk for depression. We examined whether never-disordered daughters whose mothers have experienced recurrent episodes of depression during their daughters' lifetime differ from never-disordered daughters of never-disordered mothers in their patterns of neural activation during a negative mood induction and during automatic mood regulation. Sad mood was induced in daughters through the use of film clips; daughters then recalled positive autobiographical memories, a procedure shown previously to repair negative affect. During the mood induction, high-risk girls exhibited greater activation than did low-risk daughters in brain areas that have frequently been implicated in the experience of negative affect, including the amygdala and ventrolateral prefrontal cortex. In contrast, during automatic mood regulation, low-risk daughters exhibited greater activation than did their high-risk counterparts in brain areas that have frequently been associated with top-down regulation of emotion, including the dorsolateral prefrontal cortex and dorsal anterior cingulate cortex. These findings indicate that girls at high and low risk for depression differ in their patterns of neural activation both while experiencing, and while repairing negative affect, and suggest that anomalies in neural functioning precede the onset of a depressive episode.

  View details for DOI 10.1037/a0025294

  View details for Web of Science ID 000300198500007

  View details for PubMedID 21895344

  View details for PubMedCentralID PMC3279705

• Reduced sleep quality in healthy girls at risk for depression JOURNAL OF SLEEP RESEARCH Chen, M. C., Burley, H. W., Gotlib, I. H. 2012; 21 (1): 68-72

  Abstract

  Depression is characterized by sleep difficulties, but the extent to which subjective and objective sleep disturbances precede depression are unclear. This study was designed to examine perceptions of sleep quality in addition to actigraphy- and diary-measured sleep variables in healthy girls at low and high familial risk for major depressive disorder. Forty-four healthy daughters and their mothers completed a week of daily sleep diary and actigraphy; 24 girls had mothers with no history of psychopathology (low risk, mean age 14.92 years), and 20 girls had mothers with recurrent depression during the daughter's lifetime (high risk, mean age 14.12 years). All daughters had no current or past psychopathology. High-risk girls reported significantly poorer subjective sleep quality than did low-risk girls (P = 0.001). The two groups of participants did not differ in actigraphy- or diary-measured sleep duration, onset latency or snooze duration. Healthy girls at high familial risk for depression report poorer sleep quality than do girls at low risk for depression, despite the absence of group differences in objective sleep disturbances as measured by actigraphy or daily diary. This pattern of findings may reflect a broader cognitive or physiological phenotype of risk for depression.

  View details for DOI 10.1111/j.1365-2869.2011.00934.x

  View details for PubMedID 21702865

• Anticipatory Pleasure Predicts Motivation for Reward in Major Depression JOURNAL OF ABNORMAL PSYCHOLOGY Sherdell, L., Waugh, C. E., Gotlib, I. H. 2012; 121 (1): 51-60

  Abstract

  Anhedonia, the lack of interest or pleasure in response to hedonic stimuli or experiences, is a cardinal symptom of depression. This deficit in hedonic processing has been posited to influence depressed individuals' motivation to engage in potentially rewarding experiences. Accumulating evidence indicates that hedonic processing is not a unitary construct but rather consists of an anticipatory and a consummatory phase. We examined how these components of hedonic processing influence motivation to obtain reward in participants diagnosed with major depression and in never-disordered controls. Thirty-eight currently depressed and 30 never-disordered control participants rated their liking of humorous and nonhumorous cartoons and then made a series of choices between viewing a cartoon from either group. Each choice was associated with a specified amount of effort participants would have to exert before viewing the chosen cartoon. Although depressed and control participants did not differ in their consummatory liking of the rewards, levels of reward liking predicted motivation to expend effort for the rewards only in the control participants; in the depressed participants, liking and motivation were dissociated. In the depressed group, levels of anticipatory anhedonia predicted motivation to exert effort for the rewards. These findings support the formulation that anhedonia is not a unitary construct and suggest that, for depressed individuals, deficits in motivation for reward are driven primarily by low anticipatory pleasure and not by decreased consummatory liking.

  View details for DOI 10.1037/a0024945

  View details for Web of Science ID 000300198500006

  View details for PubMedID 21842963

  View details for PubMedCentralID PMC3335300

• Cognitive and neural aspects of information processing in major depressive disorder: an integrative perspective. Frontiers in psychology Foland-Ross, L. C., Gotlib, I. H. 2012; 3: 489-?

  Abstract

  Researchers using experimental paradigms to examine cognitive processes have demonstrated that Major Depressive Disorder (MDD) is associated not with a general deficit in cognitive functioning, but instead with more specific anomalies in the processing of negatively valenced material. Indeed, cognitive theories of depression posit that negative biases in the processing of information play a critical role in influencing the onset, maintenance, and recurrence of depressive episodes. In this paper we review findings from behavioral studies documenting that MDD is associated with specific difficulties in attentional disengagement from negatively valenced material, with tendencies to interpret information in a negative manner, with deficits in cognitive control in the processing of negative material, and with enhanced memory for negative material. To gain a better understanding of the neurobiological basis of these abnormalities, we also examine findings from functional neuroimaging studies of depression and show that dysfunction in neural systems that subserve emotion processing, inhibition, and attention may underlie and contribute to the deficits in cognition that have been documented in depressed individuals. Finally, we briefly review evidence from studies of children who are at high familial risk for depression that indicates that abnormalities in cognition and neural function are observable before the onset of MDD and, consequently, may represent a risk factor for the development of this disorder. By integrating research from cognitive and neural investigations of depression, we can gain a more comprehensive understanding not only of how cognitive and biological factors interact to affect the onset, maintenance, and course of MDD, but also of how such research can aid in the development of targeted strategies for the prevention and treatment of this debilitating disorder.

  View details for DOI 10.3389/fpsyg.2012.00489

  View details for PubMedID 23162521

  View details for PubMedCentralID PMC3495336

• Behavioral and neural correlates of delay of gratification 40 years later: Proc. Natl. Acad. Sci. U.S.A. 2011, Vol 108 No. 36:14998-5003. Annals of neurosciences Casey, B. J., Somerville, L. H., Gotlib, I. H., Ayduk, O., Franklin, N. T., Askrend, M. K., Jonides, J., Berman, M. G., Wilson, N. L., Teslovich, T., Glover, G., Zayas, V., Mischel, W., Shoda, Y. 2012; 19 (1): 27-28

  View details for DOI 10.5214/ans.0972.7531.180407

  View details for PubMedID 25205959

  View details for PubMedCentralID PMC4117069

• Cognitive and neural aspects of information processing in major depressive disorder: an integrative perspective FRONTIERS IN PSYCHOLOGY Foland-Ross, L. C., Gotlib, I. H. 2012; 3

  Abstract

  Researchers using experimental paradigms to examine cognitive processes have demonstrated that Major Depressive Disorder (MDD) is associated not with a general deficit in cognitive functioning, but instead with more specific anomalies in the processing of negatively valenced material. Indeed, cognitive theories of depression posit that negative biases in the processing of information play a critical role in influencing the onset, maintenance, and recurrence of depressive episodes. In this paper we review findings from behavioral studies documenting that MDD is associated with specific difficulties in attentional disengagement from negatively valenced material, with tendencies to interpret information in a negative manner, with deficits in cognitive control in the processing of negative material, and with enhanced memory for negative material. To gain a better understanding of the neurobiological basis of these abnormalities, we also examine findings from functional neuroimaging studies of depression and show that dysfunction in neural systems that subserve emotion processing, inhibition, and attention may underlie and contribute to the deficits in cognition that have been documented in depressed individuals. Finally, we briefly review evidence from studies of children who are at high familial risk for depression that indicates that abnormalities in cognition and neural function are observable before the onset of MDD and, consequently, may represent a risk factor for the development of this disorder. By integrating research from cognitive and neural investigations of depression, we can gain a more comprehensive understanding not only of how cognitive and biological factors interact to affect the onset, maintenance, and course of MDD, but also of how such research can aid in the development of targeted strategies for the prevention and treatment of this debilitating disorder.

  View details for DOI 10.3389/fpsyg.2012.00489

  View details for Web of Science ID 000208864000198

  View details for PubMedCentralID PMC3495336

• Neural temporal dynamics of stress in comorbid major depressive disorder and social anxiety disorder. Biology of mood & anxiety disorders Waugh, C. E., Hamilton, J. P., Chen, M. C., Joormann, J., Gotlib, I. H. 2012; 2 (1): 11-?

  Abstract

  Despite advances in neurobiological research on Major Depressive Disorder and Social Anxiety Disorder, little is known about the neural functioning of individuals with comorbid depression/social anxiety. We examined the timing of neural responses to social stress in individuals with major depression and/or social anxiety. We hypothesized that having social anxiety would be associated with earlier responses to stress, having major depression would be associated with sustained responses to stress, and that comorbid participants would exhibit both of these response patterns.Participants were females diagnosed with pure depression (n = 12), pure social anxiety (n = 16), comorbid depression/social anxiety (n = 17), or as never having had any Axis-I disorder (control; n = 17). Blood oxygenation-level dependent activity (BOLD) was assessed with functional magnetic resonance imaging (fMRI). To induce social stress, participants prepared a speech that was ostensibly to be evaluated by a third party.Whereas being diagnosed with depression was associated with a resurgence of activation in the medial frontal cortex late in the stressor, having social anxiety was associated with a vigilance-avoidance activation pattern in the occipital cortex and insula. Comorbid participants exhibited activation patterns that generally overlapped with the non-comorbid groups, with the exception of an intermediate level of activation, between the level of activation of the pure depression and social anxiety groups, in the middle and posterior cingulate cortex.These findings advance our understanding of the neural underpinnings of major depression and social anxiety, and of their comorbidity. Future research should elucidate more precisely the behavioral correlates of these patterns of brain activation.

  View details for DOI 10.1186/2045-5380-2-11

  View details for PubMedID 22738335

  View details for PubMedCentralID PMC3583464

• The effects of optimism and pessimism on updating emotional information in working memory COGNITION & EMOTION Levens, S. M., Gotlib, I. H. 2012; 26 (2): 341-350

  Abstract

  In the present study we elucidate the emotional and executive control interactions that might underlie optimism and pessimism. Participants completed a self-report measure of optimism/pessimism and performed an emotion faces categorisation task and an emotion n-back task in which they indicated whether each of a series of faces had the same or a different emotional expression (happy, sad, neutral) as the face presented two trials before. Trials were structured to measure latency to update emotional content in working memory (WM). More pessimistic individuals formed connections among positive stimuli, and broke connections among positive and sad stimuli, in WM more slowly than did less pessimistic individuals; levels of optimism/pessimism did not affect the rate with which individuals formed and broke connections among neutral representations in WM. It appears, therefore, that levels of pessimism are related to specific affective cognitive mechanisms in WM that may be involved in emotion regulation.

  View details for DOI 10.1080/02699931.2011.574110

  View details for Web of Science ID 000301650700012

  View details for PubMedID 22233460

• Sensitivity to reward and punishment in major depressive disorder: Effects of rumination and of single versus multiple experiences COGNITION & EMOTION Whitmer, A. J., Frank, M. J., Gotlib, I. H. 2012; 26 (8): 1475-1485

  Abstract

  In the current study, we examined the postulation that rumination makes it difficult for depressed individuals to learn the exact probability that different stimuli will be associated with punishment. To do so, we induced rumination or distraction in depressed and never-depressed participants and then measured punishment and reward sensitivity with a probabilistic selection task. In this task, participants first learn the probability that different stimuli will be associated with reward and punishment. During a subsequent test phase in which novel combinations of stimuli are presented, participants' sensitivity to reward is tested by measuring their tendency to select the stimuli that were most highly rewarded during training, and their sensitivity to punishment is tested by measuring their tendency to not select the stimuli that were most highly punished during training. Compared with distraction, rumination led depressed participants to be less sensitive to the probability that stimuli will be associated with punishment and relatively less sensitive to punishment than reward. Never-depressed participants and depressed participants who were distracted from rumination were as sensitive to reward as they were to punishment. The effects of rumination on sensitivity to punishment may be a mechanism by which rumination can lead to maladaptive consequences.

  View details for DOI 10.1080/02699931.2012.682973

  View details for Web of Science ID 000310736900009

  View details for PubMedID 22716241

• Bringing Genetics Back to Psychiatric Endophenotypes BIOLOGICAL PSYCHIATRY Gotlib, I. H., Hamilton, J. P. 2012; 71 (1): 2-3

  View details for DOI 10.1016/j.biopsych.2011.10.033

  View details for Web of Science ID 000298137400003

  View details for PubMedID 22137155

• Concurrent and Prospective Relations Between Attention to Emotion and Affect Intensity: An Experience Sampling Study EMOTION Thompson, R. J., Mata, J., Jaeggi, S. M., Buschkuehl, M., Jonides, J., Gotlib, I. H. 2011; 11 (6): 1489-1494

  Abstract

  Theorists contend that emotional awareness is vital to being able to use emotional information adaptively. The extent to which individuals attend to and value their feelings, or attention to emotion, is a facet of emotional awareness. Little research, however, has examined whether attention to emotion affects the magnitude or intensity of emotional experiences. In the present study we examined the relations between attention to emotion and levels of affect in 53 healthy adults. Participants carried hand-held electronic devices for approximately 7 days and were randomly prompted eight times per day to answer a series of questions. At each prompt, participants reported attention to emotion, current negative affect (NA), and positive affect (PA). All findings presented were computed using multilevel modeling. Replicating findings obtained using trait-level measures, we found that attention to emotion was associated concurrently with higher levels of both NA and PA. We also found prospectively that attention to emotion at one prompt predicted a decrease in levels of NA, but no change in levels of PA, at the subsequent prompt. These findings suggest that emotional processes serve different functions over time and highlight the role of attention to emotion in affect regulation. (PsycINFO Database Record (c) 2011 APA, all rights reserved).

  View details for DOI 10.1037/a0022822

  View details for Web of Science ID 000297921200028

  View details for PubMedID 21534663

  View details for PubMedCentralID PMC3204007

• Altered Structural Brain Connectivity in Healthy Carriers of the Autism Risk Gene, CNTNAP2 BRAIN CONNECTIVITY Dennis, E. L., Jahanshad, N., Rudie, J. D., Brown, J. A., Johnson, K., McMahon, K. L., de Zubicaray, G., Montgomery, G., Martin, N. G., Wright, M. J., Bookheimer, S. Y., Dapretto, M., Toga, A. W., Thompson, P. M. 2011; 1 (6): 447–59

  Abstract

  Recently, carriers of a common variant in the autism risk gene, CNTNAP2, were found to have altered functional brain connectivity using functional MRI. Here, we scanned 328 young adults with high-field (4-Tesla) diffusion imaging, to test the hypothesis that carriers of this gene variant would have altered structural brain connectivity. All participants (209 women, 119 men, age: 23.4±2.17 SD years) were scanned with 105-gradient high-angular-resolution diffusion imaging (HARDI) at 4 Tesla. After performing a whole-brain fiber tractography using the full angular resolution of the diffusion scans, 70 cortical surface-based regions of interest were created from each individual's co-registered anatomical data to compute graph metrics for all pairs of cortical regions. In graph theory analyses, subjects homozygous for the risk allele (CC) had lower characteristic path length, greater small-worldness and global efficiency in whole-brain analyses, and lower [corrected] eccentricity (maximum path length) in 60 of the 70 nodes in regional analyses. These results were not reducible to differences in more commonly studied traits such as fiber density or fractional anisotropy. This is the first study that links graph theory metrics of brain structural connectivity to a common genetic variant linked with autism and will help us understand the neurobiology of the circuits implicated in the risk for autism.

  View details for DOI 10.1089/brain.2011.0064

  View details for Web of Science ID 000448101700002

  View details for PubMedID 22500773

  View details for PubMedCentralID PMC3420970

• Vector autoregression, structural equation modeling, and their synthesis in neuroimaging data analysis COMPUTERS IN BIOLOGY AND MEDICINE Chen, G., Glen, D. R., Saad, Z. S., Hamilton, J. P., Thomason, M. E., Gotlib, I. H., Cox, R. W. 2011; 41 (12): 1142-1155

  Abstract

  Vector autoregression (VAR) and structural equation modeling (SEM) are two popular brain-network modeling tools. VAR, which is a data-driven approach, assumes that connected regions exert time-lagged influences on one another. In contrast, the hypothesis-driven SEM is used to validate an existing connectivity model where connected regions have contemporaneous interactions among them. We present the two models in detail and discuss their applicability to FMRI data, and their interpretational limits. We also propose a unified approach that models both lagged and contemporaneous effects. The unifying model, structural vector autoregression (SVAR), may improve statistical and explanatory power, and avoid some prevalent pitfalls that can occur when VAR and SEM are utilized separately.

  View details for DOI 10.1016/j.compbiomed.2011.09.004

  View details for Web of Science ID 000298200700011

  View details for PubMedID 21975109

  View details for PubMedCentralID PMC3223325

• Characterization and Factors Associated with Sleep Quality in Adolescents with Bipolar I Disorder CHILD PSYCHIATRY & HUMAN DEVELOPMENT Roybal, D. J., Chang, K. D., Chen, M. C., Howe, M. E., Gotlib, I. H., Singh, M. K. 2011; 42 (6): 724-740

  Abstract

  Sleep disturbance is an early marker for bipolar disorder (BD) onset in youth. We characterized sleep quality in adolescents experiencing mania within the last 6-12 months. We examined the association between mood and sleep in 27 adolescents with BD and 24 matched healthy controls (HC). Subjects were assessed by parent and teen report of sleep, a semi-structured clinical interview, the Young Mania Rating Scale (YMRS), and the Childhood Depression Rating Scale (CDRS-R). Average BD youth YMRS (mean 20.3 ± 7.3) and CDRS-R (mean 42.4 ± 14.1) scores indicated they were still ill at time of assessment. Compared to HCs, adolescents with BD have distinct patterns of prolonged sleep onset latency, frequent nighttime awakenings, and increased total time awake. Mood symptoms, specifically excessive guilt, self-injurious behavior, and worsening evening mood, interfered with sleep. Further studies are needed to determine whether early regulation of sleep would improve long-term outcome in BD youth.

  View details for DOI 10.1007/s10578-011-0239-0

  View details for PubMedID 21701911

• Stress-induced activation of the HPA axis predicts connectivity between subgenual cingulate and salience network during rest in adolescents JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY Thomason, M. E., Hamilton, J. P., Gotlib, I. H. 2011; 52 (10): 1026-1034

  Abstract

  Responses to stress vary greatly in young adolescents, and little is known about neural correlates of the stress response in youth. The purpose of this study was to examine whether variability in cortisol responsivity following a social stress test in young adolescents is associated with altered neural functional connectivity (FC) of the salience network (SN) measured during resting-state functional magnetic resonance imaging (rs-fMRI).Forty-nine typically developing young adolescents participated in a social stress test during which they contributed salivary cortisol samples. Following this, they underwent rs-fMRI scanning. We examined the association of FC of the SN [composed of anterior cingulate cortex and bilateral anterior insula regions] with cortisol responsivity.Greater cortisol responsivity was significantly positively correlated with higher FC between subgenual anterior cingulate cortex (Cg25) and the SN, controlling for participant age. There were no regions of the brain that showed an inverse relation.Brain systems that have been implicated in autonomic arousal and that influence subjective feeling states show altered FC associated with stress responsivity in early life.

  View details for DOI 10.1111/j.1469-7610.2011.02422.x

  View details for Web of Science ID 000295119700003

  View details for PubMedID 21644985

  View details for PubMedCentralID PMC3169772

• Flexible Emotional Responsiveness in Trait Resilience EMOTION Waugh, C. E., Thompson, R. J., Gotlib, I. H. 2011; 11 (5): 1059-1067

  Abstract

  Field studies and laboratory experiments have documented that a key component of resilience is emotional flexibility--the ability to respond flexibly to changing emotional circumstances. In the present study we tested the hypotheses that resilient people exhibit emotional flexibility: (a) in response to frequently changing emotional stimuli and (b) across multiple modalities of emotional responding. As participants viewed a series of emotional pictures, we assessed their self-reported affect, facial muscle activity, and startle reflexes. Higher trait resilience predicted more divergent affective and facial responses (corrugator and zygomatic) to positive versus negative pictures. Thus, compared with their low-resilient counterparts, resilient people appear to be able to more flexibly match their emotional responses to the frequently changing emotional stimuli. Moreover, whereas high-trait-resilient participants exhibited divergent startle responses to positive versus negative pictures regardless of the valence of the preceding trial, low-trait-resilient participants did not exhibit divergent startle responses when the preceding picture was negative. High-trait-resilient individuals, therefore, appear to be better able than are their low-resilient counterparts to either switch or maintain their emotional responses depending on whether the emotional context changes. The present findings broaden our understanding of the mechanisms underlying resilience by demonstrating that resilient people are able to flexibly change their affective and physiological responses to match the demands of frequently changing environmental circumstances.

  View details for DOI 10.1037/a0021786

  View details for Web of Science ID 000295372600006

  View details for PubMedID 21707168

  View details for PubMedCentralID PMC3183326

• Behavioral and neural correlates of delay of gratification 40 years later PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Casey, B. J., Somerville, L. H., Gotlib, I. H., Ayduk, O., Franklin, N. T., Askren, M. K., Jonides, J., Berman, M. G., Wilson, N. L., Teslovich, T., Glover, G., Zayas, V., Mischel, W., Shoda, Y. 2011; 108 (36): 14998-15003

  Abstract

  We examined the neural basis of self-regulation in individuals from a cohort of preschoolers who performed the delay-of-gratification task 4 decades ago. Nearly 60 individuals, now in their mid-forties, were tested on "hot" and "cool" versions of a go/nogo task to assess whether delay of gratification in childhood predicts impulse control abilities and sensitivity to alluring cues (happy faces). Individuals who were less able to delay gratification in preschool and consistently showed low self-control abilities in their twenties and thirties performed more poorly than did high delayers when having to suppress a response to a happy face but not to a neutral or fearful face. This finding suggests that sensitivity to environmental hot cues plays a significant role in individuals' ability to suppress actions toward such stimuli. A subset of these participants (n = 26) underwent functional imaging for the first time to test for biased recruitment of frontostriatal circuitry when required to suppress responses to alluring cues. Whereas the prefrontal cortex differentiated between nogo and go trials to a greater extent in high delayers, the ventral striatum showed exaggerated recruitment in low delayers. Thus, resistance to temptation as measured originally by the delay-of-gratification task is a relatively stable individual difference that predicts reliable biases in frontostriatal circuitries that integrate motivational and control processes.

  View details for DOI 10.1073/pnas.1108561108

  View details for Web of Science ID 000294543400057

  View details for PubMedID 21876169

  View details for PubMedCentralID PMC3169162

• Early parental loss and depression history: Associations with recent life stress in major depressive disorder JOURNAL OF PSYCHIATRIC RESEARCH Slavich, G. M., Monroe, S. M., Gotlib, I. H. 2011; 45 (9): 1146-1152

  Abstract

  Although exposure to early adversity and prior experiences with depression have both been associated with lower levels of precipitating life stress in depression, it is unclear whether these stress sensitization effects are similar for all types of stress or whether they are specific to stressors that may be particularly depressogenic, such as those involving interpersonal loss. To investigate this issue, we administered structured, interview-based measures of early adversity, depression history, and recent life stress to one hundred adults who were diagnosed with major depressive disorder. As predicted, individuals who experienced early parental loss or prolonged separation (i.e., lasting one year or longer) and persons with more lifetime episodes of depression became depressed following lower levels of life stress occurring in the etiologically-central time period of three months prior to onset of depression. Importantly, however, additional analyses revealed that these effects were unique to stressors involving interpersonal loss. These data highlight potential stressor-specific effects in stress sensitization and demonstrate for the first time that individuals exposed to early parental loss or separation, and persons with greater histories of MDD, may be selectively sensitized to stressors involving interpersonal loss.

  View details for DOI 10.1016/j.jpsychires.2011.03.004

  View details for Web of Science ID 000294885400003

  View details for PubMedID 21470621

  View details for PubMedCentralID PMC3143306

• The effects of postnatal maternal depression and anxiety on the processing of infant faces JOURNAL OF AFFECTIVE DISORDERS Arteche, A., Joormann, J., Harvey, A., Craske, M., Gotlib, I. H., Lehtonen, A., Counsell, N., Stein, A. 2011; 133 (1-2): 197-203

  Abstract

  Postnatally depressed mothers have difficulties responding appropriately to their infants. The quality of the mother-child relationship depends on a mother's ability to respond to her infant's cues, which are largely non-verbal. Therefore, it is likely that difficulties in a mother's appraisal of her infants' facial expressions will affect the quality of mother-infant interaction. This study aimed to investigate the effects of postnatal depression and anxiety on the processing of infants' facial expressions.A total of 89 mothers, 34 with Generalised Anxiety Disorder, 21 with Major Depressive Disorder, and 34 controls, completed a 'morphed infants' faces task when their children were between 10 and 18 months.Overall, mothers were more likely to identify happy faces accurately and at lower intensity than sad faces. Depressed compared to control participants, however, were less likely to accurately identify happy infant faces. Interestingly, mothers with GAD tended to identify happy faces at a lower intensity than controls. There were no differences between the groups in relation to sad faces.Our sample was relatively small and further research is needed to investigate the links between mothers' perceptions of infant expressions and both maternal responsiveness and later measures of child development.Our findings have potential clinical implications as the difficulties in the processing of positive facial expressions in depression may lead to less maternal responsiveness to positive affect in the offspring and may diminish the quality of the mother-child interactions. Results for participants with GAD are consistent with the literature demonstrating that persons with GAD are intolerant of uncertainty and seek reassurance due to their worries.

  View details for DOI 10.1016/j.jad.2011.04.015

  View details for Web of Science ID 000294934700024

  View details for PubMedID 21641652

  View details for PubMedCentralID PMC3161178

• Default-Mode and Task-Positive Network Activity in Major Depressive Disorder: Implications for Adaptive and Maladaptive Rumination BIOLOGICAL PSYCHIATRY Hamilton, J. P., Furman, D. J., Chang, C., Thomason, M. E., Dennis, E., Gotlib, I. H. 2011; 70 (4): 327-333

  Abstract

  Major depressive disorder (MDD) has been associated reliably with ruminative responding; this kind of responding is composed of both maladaptive and adaptive components. Levels of activity in the default-mode network (DMN) relative to the task-positive network (TPN), as well as activity in structures that influence DMN and TPN functioning, may represent important neural substrates of maladaptive and adaptive rumination in MDD.We used a unique metric to estimate DMN dominance over TPN from blood oxygenation level-dependent data collected during eyes-closed rest in 17 currently depressed and 17 never-disordered adults. We calculated correlations between this metric of DMN dominance over TPN and the depressive, brooding, and reflective subscales of the Ruminative Responses Scale, correcting for associations between these measures both with one another and with severity of depression. Finally, we estimated and compared across groups right fronto-insular cortex (RFIC) response during initiations of ascent in DMN and in TPN activity.In the MDD participants, increasing levels of DMN dominance were associated with higher levels of maladaptive, depressive rumination and lower levels of adaptive, reflective rumination. Moreover, our RFIC state-change analysis showed increased RFIC activation in the MDD participants at the onset of increases in TPN activity; conversely, healthy control participants exhibited increased RFIC response at the onset of increases in DMN activity.These findings support a formulation in which the DMN undergirds representation of negative, self-referential information in depression, and the RFIC, when prompted by increased levels of DMN activity, initiates an adaptive engagement of the TPN.

  View details for DOI 10.1016/j.biopsych.2011.02.003

  View details for Web of Science ID 000293080400011

  View details for PubMedID 21459364

  View details for PubMedCentralID PMC3144981

• Sticky Thoughts: Depression and Rumination Are Associated With Difficulties Manipulating Emotional Material in Working Memory PSYCHOLOGICAL SCIENCE Joormann, J., Levens, S. M., Gotlib, I. H. 2011; 22 (8): 979-983

  Abstract

  Cognitive inflexibility may play an important role in rumination, a risk factor for the onset and maintenance of depressive episodes. In the study reported here, we assessed participants' ability to either reverse or maintain in working memory the order of three emotion or three neutral words. Differences (or sorting costs) between response latencies in backward trials, on which participants were asked to reverse the order of the words, and forward trials, on which participants were asked to remember the words in the order in which they were presented, were calculated. Compared with control participants, depressed participants had higher sorting costs, particularly when presented with negative words. It is important to note that rumination predicted sorting costs for negative words but not for positive or neutral words in the depressed group. These findings indicate that depression and rumination are associated with deficits in cognitive control.

  View details for DOI 10.1177/0956797611415539

  View details for Web of Science ID 000294709400001

  View details for PubMedID 21742932

• 5-HTTLPR Moderates the Relation between Changes in Depressive and Bulimic Symptoms in Adolescent Girls: A Longitudinal Study INTERNATIONAL JOURNAL OF EATING DISORDERS Mata, J., Gotlib, I. H. 2011; 44 (5): 383-388

  Abstract

  Depression and bulimia both are associated with low serotonin levels. We examined whether the serotonin transporter gene (5-HTTLPR) moderates the relation between depressive and bulimic symptoms over time.Fifty adolescent girls with no current or past Axis I disorder were genotyped for the 5-HTTLPR gene. Twice, 6 months apart, participants completed self-report measures of depressive symptoms and bulimic symptoms.The association between change in depressive symptoms and change in bulimic symptoms over time was significantly stronger in girls who are homozygous for the short 5-HTTLPR allele than for girls with at least one long allele.This finding is consistent with previous studies documenting a relation between depressive and bulimic symptoms in adolescents. Few studies, however, considered the possible role of serotonin linking both disorders. Gaining a better understanding of developmental effects of low serotonin could help to identify high-risk individuals and provide effective prevention and intervention.

  View details for DOI 10.1002/eat.20850

  View details for Web of Science ID 000291614200001

  View details for PubMedID 21661000

• Investigating neural primacy in Major Depressive Disorder: multivariate Granger causality analysis of resting-state fMRI time-series data MOLECULAR PSYCHIATRY Hamilton, J. P., Chen, G., Thomason, M. E., Schwartz, M. E., Gotlib, I. H. 2011; 16 (7): 763-772

  Abstract

  Major Depressive Disorder (MDD) has been conceptualized as a neural network-level disease. Few studies of the neural bases of depression, however, have used analytical techniques that are capable of testing network-level hypotheses of neural dysfunction in this disorder. Moreover, of those that have, fewer still have attempted to determine the directionality of influence within functionally abnormal networks of structures. We used multivariate GC analysis, a technique that estimates the extent to which preceding neural activity in one or more seed regions predicts subsequent activity in target brain regions, to analyze blood-oxygen-level-dependent (BOLD) data collected during eyes-closed rest from depressed and never-depressed persons. We found that activation in the hippocampus predicted subsequent increases in ventral anterior cingulate cortex (vACC) activity in depression, and that activity in the medial prefrontal cortex and vACC were mutually reinforcing in MDD. Hippocampal and vACC activation in depressed participants predicted subsequent decreases in dorsal cortical activity. This study shows that, on a moment-by-moment basis, there is increased excitatory activity among limbic and paralimbic structures, as well as increased inhibition in the activity of dorsal cortical structures, by limbic structures in depression; these aberrant patterns of effective connectivity implicate disturbances in the mesostriatal dopamine system in depression. These findings advance the neural theory of depression by detailing specific patterns of limbic excitation in MDD, by making explicit the primary role of limbic inhibition of dorsal cortex in the cortico-limbic relation posited to underlie depression, and by presenting an integrated neurofunctional account of altered dopamine function in this disorder.

  View details for DOI 10.1038/mp.2010.46

  View details for Web of Science ID 000291973300011

  View details for PubMedID 20479758

• Variant in oxytocin receptor gene is associated with amygdala volume PSYCHONEUROENDOCRINOLOGY Furman, D. J., Chen, M. C., Gotlib, I. H. 2011; 36 (6): 891-897

  Abstract

  The oxytocin system plays a significant role in modulating stress responses in animals and humans; perturbations in this system may contribute to the pathogenesis of psychiatric disorder. Attempts to identify clinically relevant genetic variants in the oxytocin system have yielded associations between polymorphisms of the oxytocin receptor (OXTR) gene and both autism and major depression. To date, however, little is known about how such variants affect brain structures implicated in these disorders. Applying a manual tracing procedure to high-resolution structural magnetic resonance images, amygdala volumes were measured in 51 girls genotyped on OXTR rs2254298(G>A), a single nucleotide polymorphism associated with psychopathology. Results of this study indicate that despite having greater gray matter volume, participants homozygous for the G allele were characterized by smaller volumes of both left and right amygdala than were carriers of the A allele. A subsequent whole-brain voxel-based morphometry analysis revealed additional genotype-mediated volumetric group differences in the posterior brain stem and dorsomedial anterior cingulate cortex. These findings highlight one neurobiological pathway by which oxytocin gene variants may increase risk for psychopathology. Further research is needed to characterize the mechanism by which this polymorphism contributes to anatomical variability and to identify functional correlates of these alterations in regional brain volume.

  View details for DOI 10.1016/j.psyneuen.2010.12.004

  View details for PubMedID 21208749

• Life stress and first onset of psychiatric disorders in daughters of depressed mothers JOURNAL OF PSYCHIATRIC RESEARCH Gershon, A., Hayward, C., Schraedley-Desmond, P., Rudolph, K. D., Booster, G. D., Gotlib, I. H. 2011; 45 (7): 855-862

  Abstract

  This study used a comprehensive, interview-based measure of life stress to assess the role of different types of stress in predicting first onset of psychiatric disorders among daughters of depressed (n = 22) mothers and healthy (n = 22) mothers. Several types of stress were assessed: Chronic interpersonal stress, chronic non-interpersonal stress, episodic dependent (i.e., self-generated) interpersonal stress, episodic dependent non-interpersonal stress, episodic independent interpersonal stress, and episodic independent non-interpersonal stress. Daughters (ages 9-14) were recruited to have no clinically significant symptoms upon entry (T1). By a 30-month follow-up assessment (T2), 45% of the daughters of depressed mothers, but none of the daughters of healthy mothers, had developed a psychiatric disorder. Overall, daughters of depressed mothers were exposed to more severe chronic interpersonal and non-interpersonal stress than were daughters of healthy mothers. Further, daughters of depressed mothers who developed a psychiatric disorder by T2 were exposed to more severe chronic non-interpersonal stress and episodic dependent stress than were daughters of depressed mothers who remained healthy. We discuss the implications of these findings in the context of a stress-generation model for the intergenerational transmission of psychiatric risk among children of depressed mothers.

  View details for DOI 10.1016/j.jpsychires.2011.03.016

  View details for Web of Science ID 000292667900001

  View details for PubMedID 21524424

  View details for PubMedCentralID PMC3115484

• Altered timing of amygdala activation during sad mood elaboration as a function of 5-HTTLPR SOCIAL COGNITIVE AND AFFECTIVE NEUROSCIENCE Furman, D. J., Hamilton, J. P., Joormann, J., Gotlib, I. H. 2011; 6 (3): 270-276

  Abstract

  A functional variant of the serotonin transporter gene (5-HTTLPR) has been associated with increased risk for major depression in the context of stress. In attempting to understand the mechanisms underlying this relation, we tested the hypothesis that 5-HTTLPR genotype affects the speed with which amygdala is recruited during emotional processing in young girls with no history of psychiatric disorder. We used functional magnetic resonance imaging to compare the rise time to peak amygdala activation in 5-HTTLPR short-allele carriers and long-allele homozygotes during enhancement of sad mood. Relative to long-allele homozygotes, participants with at least one copy of the 5-HTTLPR short allele showed both stronger and earlier activation in left amygdala as they increased a sad mood state. Individuals carrying the short allele appear to exhibit a neural 'readiness' to engage and enhance negative affect. Future research should examine how exposure to negative life events and more chronic sadness modify the time course of amygdala activity during the experience of negative emotion.

  View details for DOI 10.1093/scan/nsq029

  View details for Web of Science ID 000291543600003

  View details for PubMedID 20360351

  View details for PubMedCentralID PMC3110425

• Quality of life and impulsivity in bipolar disorder BIPOLAR DISORDERS Victor, S. E., Johnson, S. L., Gotlib, I. H. 2011; 13 (3): 303-309

  Abstract

  Bipolar disorder (BD) is a chronic psychiatric illness that impairs quality of life (QoL) in numerous life domains even when mood symptoms are not present and is characterized by elevated impulsivity. Many of the comorbid conditions that are associated with diminished QoL in BD also involve impulsivity. The objective of this project was to investigate whether impulsivity might mediate the effects of these comorbid conditions on poor QoL.A total of 76 participants diagnosed with bipolar I disorder by the Structured Clinical Interview for DSM-IV Axis I disorders completed the Quality of Life in Bipolar Disorder (QoL-BD) scale, the Barratt Impulsivity Scale (BIS-11), and the Positive Urgency Measure (PUM). Participants were also assessed for comorbid DSM-IV diagnoses of anxiety, substance use, and impulse control disorders.Several subscales of the BIS-11 as well as the PUM total score were significantly negatively correlated with overall QoL. PUM total score remained a significant predictor of QoL after controlling for comorbid anxiety, substance use, and impulse control disorders. After controlling for impulsivity, comorbid disorders were no longer significantly related to overall QoL.The data support the hypothesis that impulsivity, specifically positive urgency, is highly correlated with QoL in BD. Impulsivity was found to mediate the relation between QoL and several comorbidities in BD. Interventions targeting impulsivity might help to improve QoL in BD.

  View details for DOI 10.1111/j.1399-5618.2011.00919.x

  View details for Web of Science ID 000292666000009

  View details for PubMedID 21676133

  View details for PubMedCentralID PMC3117247

• Individual Differences in Stress-Induced Activation of the HPA-axis Predicts Connectivity between Subgenual Cingulate and Salience Network During Resting-State fMRI in Adolescents Thomason, M. E., Hamilton, J., Burley, H. W., Gotlib, I. H. ELSEVIER SCIENCE INC. 2011: 111S

  View details for Web of Science ID 000290641800354

• Brooding and Reflection Reconsidered: A Factor Analytic Examination of Rumination in Currently Depressed, Formerly Depressed, and Never Depressed Individuals COGNITIVE THERAPY AND RESEARCH Whitmer, A., Gotlib, I. H. 2011; 35 (2): 99-107

  View details for DOI 10.1007/s10608-011-9361-3

  View details for Web of Science ID 000288800800001

• 'Willpower' over the life span: decomposing self-regulation SOCIAL COGNITIVE AND AFFECTIVE NEUROSCIENCE Mischel, W., Ayduk, O., Berman, M. G., Casey, B. J., Gotlib, I. H., Jonides, J., Kross, E., Teslovich, T., Wilson, N. L., Zayas, V., Shoda, Y. 2011; 6 (2): 252-256

  Abstract

  In the 1960s, Mischel and colleagues developed a simple 'marshmallow test' to measure preschoolers' ability to delay gratification. In numerous follow-up studies over 40 years, this 'test' proved to have surprisingly significant predictive validity for consequential social, cognitive and mental health outcomes over the life course. In this article, we review key findings from the longitudinal work and from earlier delay-of-gratification experiments examining the cognitive appraisal and attention control strategies that underlie this ability. Further, we outline a set of hypotheses that emerge from the intersection of these findings with research on 'cognitive control' mechanisms and their neural bases. We discuss implications of these hypotheses for decomposing the phenomena of 'willpower' and the lifelong individual differences in self-regulatory ability that were identified in the earlier research and that are currently being pursued.

  View details for DOI 10.1093/scan/nsq081

  View details for Web of Science ID 000291543100011

  View details for PubMedID 20855294

  View details for PubMedCentralID PMC3073393

• Neural and behavioral effects of interference resolution in depression and rumination COGNITIVE AFFECTIVE & BEHAVIORAL NEUROSCIENCE Berman, M. G., Nee, D. E., Casement, M., Kim, H. S., Deldin, P., Kross, E., Gonzalez, R., Demiralp, E., Gotlib, I. H., Hamilton, P., Joormann, J., Waugh, C., Jonides, J. 2011; 11 (1): 85-96

  Abstract

  Individuals diagnosed with major depressive disorder (MDD) often ruminate about their depression and their life situations, impairing their concentration and performance on daily tasks. We examined whether rumination might be due to a deficit in the ability to expel negative information from short-term memory (STM), and fMRI was used to examine the neural structures involved in this ability. MDD and healthy control (HC) participants were tested using a directed-forgetting procedure in a short-term item recognition task. As predicted, MDD participants had more difficulty than did HCs in expelling negative, but not positive, words from STM. Overall, the neural networks involved in directed forgetting were similar for both groups, but the MDDs exhibited more spatial variability in activation in the left inferior frontal gyrus (a region critical for inhibiting irrelevant information), which may contribute to their relative inability to inhibit negative information.

  View details for DOI 10.3758/s13415-010-0014-x

  View details for Web of Science ID 000290029000008

  View details for PubMedID 21264648

• Resting-state fMRI can reliably map neural networks in children NEUROIMAGE Thomason, M. E., Dennis, E. L., Joshi, A. A., Joshi, S. H., Dinov, I. D., Chang, C., Henry, M. L., Johnson, R. F., Thompson, P. M., Toga, A. W., Glover, G. H., Van Horn, J. D., Gotlib, I. H. 2011; 55 (1): 165-175

  Abstract

  Resting-state MRI (rs-fMRI) is a powerful procedure for studying whole-brain neural connectivity. In this study we provide the first empirical evidence of the longitudinal reliability of rs-fMRI in children. We compared rest-retest measurements across spatial, temporal and frequency domains for each of six cognitive and sensorimotor intrinsic connectivity networks (ICNs) both within and between scan sessions. Using Kendall'sW, concordance of spatial maps ranged from .60 to .86 across networks, for various derived measures. The Pearson correlation coefficient for temporal coherence between networks across all Time 1-Time 2 (T1/T2) z-converted measures was .66 (p<.001). There were no differences between T1/T2 measurements in low-frequency power of the ICNs. For the visual network, within-session T1 correlated with the T2 low-frequency power, across participants. These measures from resting-state data in children were consistent across multiple domains (spatial, temporal, and frequency). Resting-state connectivity is therefore a reliable method for assessing large-scale brain networks in children.

  View details for DOI 10.1016/j.neuroimage.2010.11.080

  View details for Web of Science ID 000287008900014

  View details for PubMedID 21134471

  View details for PubMedCentralID PMC3031732

• Memory for affectively valenced and neutral stimuli in depression: Evidence from a novel matching task COGNITION & EMOTION Gotlib, I. H., Jonides, J., Buschkuehl, M., Joormann, J. 2011; 25 (7): 1246-1254

  Abstract

  Depressed persons have better memory for affectively negative than positive stimuli, a pattern generally not exhibited by non-depressed individuals. The mechanisms underlying this differential memory are not clear. In this study we examined memory for valenced and neutral stimuli in depressed and non-depressed individuals under conditions of relatively unconstrained encoding. We developed a novel task based on the game, Concentration, in which participants tried to match pairs of positive and negative words, and pairs of neutral words, hidden under squares in as few turns as possible. Whereas non-depressed participants selected and turned over positive squares more frequently than they did negative squares, depressed participants selected and turned over positive and negative squares equally often. Depressed participants also matched fewer positive word pairs within the first five minutes of the task than did non-depressed participants, and they exhibited poorer learning of positive words. Depressed and non-depressed participants did not differ in their matching of neutral words. These findings add to a growing literature indicating that depression is characterised by difficulties in the processing of positive stimuli.

  View details for DOI 10.1080/02699931.2010.538374

  View details for Web of Science ID 000299564700010

  View details for PubMedID 21432643

• Oxytocin Receptor (OXTR) Polymorphisms and Attachment in Human Infants. Frontiers in psychology Chen, F. S., Barth, M. E., Johnson, S. L., Gotlib, I. H., Johnson, S. C. 2011; 2: 200-?

  Abstract

  Ordinary variations in human infants' attachment behaviors - their proclivity to seek and accept comfort from caregivers - are associated with a wide range of individual differences in psychological functioning in adults. The current investigation examined variation in the oxytocin receptor (OXTR) gene as one possible source of these variations in infant attachment. One hundred seventy-six infants (77 Caucasian, 99 non-Caucasian) were classified as securely or insecurely attached based on their behavior in the Strange Situation (Ainsworth et al., 1978). The A allele of OXTR rs2254298 was associated with attachment security in the non-Caucasian infants (p < 0.005). These findings underscore the importance of oxytocin in the development of human social behavior and support its role in social stress-regulation and the development of trust.

  View details for DOI 10.3389/fpsyg.2011.00200

  View details for PubMedID 21904531

• Attentional Biases for Emotional Faces in Young Children of Mothers with Chronic or Recurrent Depression JOURNAL OF ABNORMAL CHILD PSYCHOLOGY Kujawa, A. J., Torpey, D., Kim, J., Hajcak, G., Rose, S., Gotlib, I. H., Klein, D. N. 2011; 39 (1): 125-135

  Abstract

  Attentional biases for negative stimuli have been observed in school-age and adolescent children of depressed mothers and may reflect a vulnerability to depression. The direction of these biases and whether they can be identified in early childhood remains unclear. The current study examined attentional biases in 5-7-year-old children of depressed and non-depressed mothers. Following a mood induction, children participated in a dot-probe task assessing biases for sad and happy faces. There was a significant interaction of group and sex: daughters of depressed mothers attended selectively to sad faces, while children of controls and sons of depressed mothers did not exhibit biases. No effects were found for happy stimuli. These findings suggest that attentional biases are discernible in early childhood and may be vulnerability markers for depression. The results also raise the possibility that sex differences in cognitive biases are evident before the emergence of sex differences in the prevalence of depression.

  View details for DOI 10.1007/s10802-010-9438-6

  View details for Web of Science ID 000287149500011

  View details for PubMedID 20644991

  View details for PubMedCentralID PMC3367881

• Oxytocin receptor (OXTR) polymorphisms and attachment in human infants FRONTIERS IN PSYCHOLOGY Chen, F. S., Barth, M. E., Johnson, S. L., Gotlib, I. H., Johnson, S. C. 2011; 2

  Abstract

  Ordinary variations in human infants' attachment behaviors - their proclivity to seek and accept comfort from caregivers - are associated with a wide range of individual differences in psychological functioning in adults. The current investigation examined variation in the oxytocin receptor (OXTR) gene as one possible source of these variations in infant attachment. One hundred seventy-six infants (77 Caucasian, 99 non-Caucasian) were classified as securely or insecurely attached based on their behavior in the Strange Situation (Ainsworth et al., 1978). The A allele of OXTR rs2254298 was associated with attachment security in the non-Caucasian infants (p < 0.005). These findings underscore the importance of oxytocin in the development of human social behavior and support its role in social stress-regulation and the development of trust.

  View details for DOI 10.3389/fpsyg.2011.00200

  View details for Web of Science ID 000208863800015

  View details for PubMedCentralID PMC3161247

• Modulation of Subgenual Anterior Cingulate Cortex Activity With Real-Time Neurofeedback HUMAN BRAIN MAPPING Hamilton, J. P., Glover, G. H., Hsu, J., Johnson, R. F., Gotlib, I. H. 2011; 32 (1): 22-31

  Abstract

  The advent of real-time neurofeedback techniques has allowed us to begin to map the controllability of sensory and cognitive and, more recently, affective centers in the brain. The subgenual anterior cingulate cortex (sACC) is thought to be involved in generation of affective states and has been implicated in psychopathology. In this study, we examined whether individuals could use real-time fMRI neurofeedback to modulate sACC activity. Following a localizer task used to identify an sACC region of interest, an experimental group of eight women participated in four scans: (1) a pretraining scan in which they were asked to decrease activity in the sACC without neurofeedback; (2) two training scans in which sACC neurofeedback was presented along with instructions to decrease sACC activity; and (3) a neurofeedback-free post-training scan. An additional nine women in a yoked feedback control group saw sACC activity from the participants in the experimental group. Activity in the sACC was significantly reduced during neurofeedback training in the experimental group, but not in the control group. This training effect in the experimental group, however, did not generalize to the neurofeedback-free post-training scan. A psychophysiological interaction analysis showed decreased correlation in the experimental group relative to the sham control group between activity in the sACC and the posterior cingulate cortex during neurofeedback training relative to neurofeedback-free scans. The finding that individuals can down-modulate the sACC shows that a primary emotion center in which functional abnormality has been strongly implicated in affective disorders can be controlled with the aid of neurofeedback.

  View details for DOI 10.1002/hbm.20997

  View details for Web of Science ID 000285398000003

  View details for PubMedID 21157877

  View details for PubMedCentralID PMC3049174

• Anxiety modulates insula recruitment in resting-state functional magnetic resonance imaging in youth and adults. Brain connectivity Dennis, E. L., Gotlib, I. H., Thompson, P. M., Thomason, M. E. 2011; 1 (3): 245-254

  Abstract

  Research on resting-state functional connectivity reveals intrinsically connected networks in the brain that are largely consistent across the general population. However, there are individual differences in these networks that have not been elucidated. Here, we measured the influence of naturally occurring mood on functional connectivity. In particular, we examined the association between self-reported levels of anxiety and connectivity in the default mode network (DMN). Healthy youth (n=43; ages 10-18) and adult participants (n=24, ages 19-59) completed a 6-min resting-state functional magnetic resonance imaging scan, then immediately completed questionnaires assessing their mood and thoughts during the scan. Regression analyses conducted separately for the youth and adult samples revealed brain regions in which increases in connectivity differentially corresponded to higher anxiety in each group. In one area, the left insular cortex, both groups showed similar increased connectivity to the DMN (youth: -30, 26, 14; adults: -33, 12, 14) with increased anxiety. State anxiety assessed during scanning was not correlated with trait anxiety, so our results likely reflect state levels of anxiety. To our knowledge, this is the first study to relate naturally occurring mood to resting state connectivity.

  View details for DOI 10.1089/brain.2011.0030

  View details for PubMedID 22433052

  View details for PubMedCentralID PMC3621677

• Frontostriatal functional connectivity in major depressive disorder. Biology of mood & anxiety disorders Furman, D. J., Hamilton, J. P., Gotlib, I. H. 2011; 1 (1): 11-?

  Abstract

  Abnormalities of the striatum and frontal cortex have been reported consistently in studies of neural structure and function in major depressive disorder (MDD). Despite speculation that compromised connectivity between these regions may underlie symptoms of MDD, little work has investigated the integrity of frontostriatal circuits in this disorder.Functional magnetic resonance images were acquired from 21 currently depressed and 19 never-disordered women during wakeful rest. Using four predefined striatal regions-of-interest, seed-to-whole brain correlations were computed and compared between groups.Compared to controls, depressed participants exhibited attenuated functional connectivity between the ventral striatum and both ventromedial prefrontal cortex and subgenual anterior cingulate cortex. Depressed participants also exhibited stronger connectivity between the dorsal caudate and dorsal prefrontal cortex, which was positively correlated with severity of the disorder.Depressed individuals are characterized by aberrant connectivity in frontostriatal circuits that are posited to support affective and cognitive processing. Further research is required to examine more explicitly the link between patterns of disrupted connectivity and specific symptoms of depression, and the extent to which these patterns precede the onset of depression and normalize with recovery from depressive illness.

  View details for DOI 10.1186/2045-5380-1-11

  View details for PubMedID 22737995

  View details for PubMedCentralID PMC3384258

• Oxytocin receptor gene polymorphism (rs2254298) interacts with familial risk for psychopathology to predict symptoms of depression and anxiety in adolescent girls PSYCHONEUROENDOCRINOLOGY Thompson, R. J., Parker, K. J., Hallmayer, J. F., Waugh, C. E., Gotlib, I. H. 2011; 36 (1): 144-147

  Abstract

  The nonapeptide oxytocin and its receptor have been implicated in the regulation of mammalian social behavior and stress physiology. Evidence is accumulating that the quality of the parental environment is associated with oxytocin biology in children. The present study was designed to examine the interaction of the single nucleotide polymorphism (SNP) rs2254298 within the oxytocin receptor (OXTR) gene and quality of parental environment in predicting children's psychosocial functioning. More specifically, in a sample of 92 Caucasian adolescent girls (9-14 years old), we examined whether adverse parental environment, operationalized as mothers' history of recurrent major depressive disorder, interacts with the rs2254298 SNP on the OXTR gene to predict daughters' symptoms of depression and anxiety. Caucasian girls who both were heterozygous for the OXTR rs2254298 polymorphism and had high early adversity reported the highest levels of symptoms of depression, physical anxiety, and social anxiety. These findings highlight the potential importance of this OXTR gene polymorphism in the etiology of depression and anxiety disorders.

  View details for DOI 10.1016/j.psyneuen.2010.07.003

  View details for Web of Science ID 000286299100016

  View details for PubMedID 20708845

  View details for PubMedCentralID PMC2997902

• Neural correlates of rumination in depression COGNITIVE AFFECTIVE & BEHAVIORAL NEUROSCIENCE Cooney, R. E., Joormann, J., Eugene, F., Dennis, E. L., Gotlib, I. H. 2010; 10 (4): 470-478

  Abstract

  Rumination, or recursive self-focused thinking, has important implications for understanding the development and maintenance of depressive episodes. Rumination is associated with the worsening of negative mood states, greater affective responding to negative material, and increased access to negative memories. The present study was designed to use fMRI to examine neural aspects of rumination in depressed and healthy control individuals. We used a rumination induction task to assess differences in patterns of neural activation during ruminative self-focus as compared with a concrete distraction condition and with a novel abstract distraction condition in 14 participants who were diagnosed with major depressive disorder and 14 healthy control participants. Depressed participants exhibited increased activation in the orbitofrontal cortex, subgenual anterior cingulate, and dorsolateral prefrontal cortex as compared with healthy controls during rumination versus concrete distraction. Neural activity during rumination versus abstract distraction was greater for depressed than for control participants in the amygdala, rostral anterior cingulate/medial prefrontal cortex, dorsolateral prefrontal cortex, posterior cingulate, and parahippocampus. These findings indicate that ruminative self-focus is associated with enhanced recruitment of limbic and medial and dorsolateral prefrontal regions in depression. Supplemental materials for this article may be downloaded from http://cabn.psychonomic-journals.org/content/supplemental.

  View details for DOI 10.3758/CABN.10.4.470

  View details for Web of Science ID 000285439000005

  View details for PubMedID 21098808

• Depression-specific information processing bias and potential relationship with dyspnea perception in patients with asthma Fritzsche, A., Dahme, B., Gotlib, I. H., Joormann, J., Magnussen, H., Watz, H., Nutzinger, D. O., von Leupoldt, A. ELSEVIER SCIENCE BV. 2010: 512–13

  View details for Web of Science ID 000287896800032

• COMT genotype affects prefrontal white matter pathways in children and adolescents NEUROIMAGE Thomason, M. E., Dougherty, R. F., Colich, N. L., Perry, L. M., Rykhlevskaia, E. I., Louro, H. M., Hallmayer, J. F., Waugh, C. E., Bammer, R., Glover, G. H., Gotlib, I. H. 2010; 53 (3): 926-934

  Abstract

  Diffusion tensor imaging is widely used to evaluate the development of white matter. Information about how alterations in major neurotransmitter systems, such as the dopamine (DA) system, influence this development in healthy children, however, is lacking. Catechol-O-metyltransferase (COMT) is the major enzyme responsible for DA degradation in prefrontal brain structures, for which there is a corresponding genetic polymorphism (val158met) that confers either a more or less efficient version of this enzyme. The result of this common genetic variation is that children may have more or less available synaptic DA in prefrontal brain regions. In the present study we examined the relation between diffusion properties of frontal white matter structures and the COMT val158met polymorphism in 40 children ages 9-15. We found that the val allele was associated with significantly elevated fractional anisotropy values and reduced axial and radial diffusivities. These results indicate that the development of white matter in healthy children is related to COMT genotype and that alterations in white matter may be related to the differential availability of prefrontal DA. This investigation paves the way for further studies of how common functional variants in the genome might influence the development of brain white matter.

  View details for DOI 10.1016/j.neuroimage.2010.01.033

  View details for Web of Science ID 000282039300015

  View details for PubMedID 20083203

  View details for PubMedCentralID PMC2902616

• Updating Positive and Negative Stimuli in Working Memory in Depression JOURNAL OF EXPERIMENTAL PSYCHOLOGY-GENERAL Levens, S. M., Gotlib, I. H. 2010; 139 (4): 654-664

  Abstract

  Difficulties in the ability to update stimuli in working memory (WM) may underlie the problems with regulating emotions that lead to the development and perpetuation of mood disorders such as depression. To examine the ability to update affective material in WM, the authors had diagnosed depressed and never-disordered control participants perform an emotion 2-back task in which participants were presented with a series of happy, sad, and neutral faces and were asked to indicate whether the current face had the same (match-set) or different (break-set or no-set) emotional expression as that presented 2 faces earlier. Participants also performed a 0-back task with the same emotional stimuli to serve as a control for perceptual processing. After transforming reaction times to control for baseline group differences, depressed and nondepressed participants exhibited biases in updating emotional content that reflects the tendency to keep negative information and positive information, respectively, active in WM. Compared with controls, depressed participants were both slower to disengage from sad stimuli and faster to disengage from happy facial expressions. In contrast, nondepressed controls took longer to disengage from happy stimuli than from neutral or sad stimuli. These group differences in reaction times may reflect both protective and maladaptive biases in WM that underlie the ability to effectively regulate negative affect.

  View details for DOI 10.1037/a0020283

  View details for Web of Science ID 000284442500006

  View details for PubMedID 21038984

  View details for PubMedCentralID PMC2984552

• Gender Differences in Life Events Prior to Onset of Major Depressive Disorder: The Moderating Effect of Age JOURNAL OF ABNORMAL PSYCHOLOGY Harkness, K. L., Alavi, N., Monroe, S. M., Slavich, G. M., Gotlib, I. H., Bagby, R. M. 2010; 119 (4): 791-803

  Abstract

  Theoretical models attempting to explain why approximately twice as many women as men suffer from depression often involve the role of stressful life events. However, detailed empirical evidence regarding gender differences in rates of life events that precede onset of depression is lacking, due in part to the common use of checklist assessments of stress that have been shown to possess poor validity. The present study reports on a combined sample of 375 individuals drawn from 4 studies in which all participants were diagnosed with major depressive disorder and assessed with the Life Events and Difficulties Schedule (Bifulco et al., 1989), a state-of-the-art contextual interview and life stress rating system. Women reported significantly more severe and nonsevere, independent and dependent, and other-focused and subject-focused life events prior to onset of depression than did men. Further, these relations were significantly moderated by age, such that gender differences in rates of most types of events were found primarily in young adulthood. These results are discussed in term of their implications for understanding the etiological role of stressful life events in depression.

  View details for DOI 10.1037/a0020629

  View details for Web of Science ID 000284247200015

  View details for PubMedID 20853920

  View details for PubMedCentralID PMC3638862

• Neural and behavioral responses to threatening emotion faces in children as a function of the short allele of the serotonin transporter gene BIOLOGICAL PSYCHOLOGY Thomason, M. E., Henry, M. L., Hamilton, J. P., Joormann, J., Pine, D. S., Ernst, M., Goldman, D., Mogg, K., Bradley, B. P., Britton, J. C., Lindstrom, K. M., Monk, C. S., Sankin, L. S., Louro, H. M., Gotlib, I. H. 2010; 85 (1): 38-44

  Abstract

  Recent evidence suggests that a genetic polymorphism in the promoter region (5-HTTLPR) of the serotonin transporter gene (SLC6A4) mediates stress reactivity in adults. Little is known, however, about this gene-brain association in childhood and adolescence, generally conceptualized as a time of heightened stress reactivity. The present study examines the association between 5-HTTLPR allelic variation and responses to fearful and angry faces presented both sub- and supraliminally in participants, ages 9-17. Behaviorally, carriers of the 5-HTTLPR short (s) allele exhibited significantly greater attentional bias to subliminally presented fear faces than did their long (l)-allele homozygous counterparts. Moreover, s-allele carriers showed greater neural activations to fearful and angry faces than did l-allele homozygotes in various regions of association cortex previously linked to attention control in adults. These results indicate that in children and adolescents, s-allele carriers can be distinguished from l-allele homozygotes on the basis of hypervigilant behavioral and neural processing of negative material.

  View details for DOI 10.1016/j.biopsycho.2010.04.009

  View details for PubMedID 20493234

• Maladaptive coping, adaptive coping, and depressive symptoms: Variations across age and depressive state BEHAVIOUR RESEARCH AND THERAPY Thompson, R. J., Mata, J., Jaeggi, S. M., Buschkuehl, M., Jonides, J., Gotlib, I. H. 2010; 48 (6): 459-466

  Abstract

  Rumination has consistently been found to be associated with the onset and duration of major depressive episodes. Little research, however, has examined factors that may weaken the association between maladaptive coping, such as rumination, and depressive symptoms. In three samples of participants, including 149 never-depressed adolescent girls, 41 never-depressed women, and 39 depressed women, we examined whether generally adaptive forms of coping interacted with generally maladaptive forms of coping to predict depressive symptoms. Age-appropriate measures of coping and depression were administered to participants in each sample. In never-depressed females, maladaptive coping/rumination were more strongly related to depressive symptoms in the presence of lower levels of adaptive coping. The relation between depression and maladaptive coping/rumination was weaker in the context of higher levels of adaptive coping. In contrast, for the depressed females, we found main effects for rumination and adaptive coping, with higher levels of rumination and lower levels of adaptive coping being associated with higher levels of depressive symptoms. The present findings highlight how adaptive coping and maladaptive coping, including rumination, differentially relate to each other and depressive symptoms depending on individuals' current depressive state.

  View details for DOI 10.1016/j.brat.2010.01.007

  View details for Web of Science ID 000278480800002

  View details for PubMedID 20211463

  View details for PubMedCentralID PMC2872051

• Emotion identification in girls at high risk for depression JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY Joormann, J., Gilbert, K., Gotlib, I. H. 2010; 51 (5): 575-582

  Abstract

  Children of depressed mothers are themselves at elevated risk for developing a depressive disorder. We have little understanding, however, of the specific factors that contribute to this increased risk. This study investigated whether never-disordered daughters whose mothers have experienced recurrent episodes of depression during their daughters' lifetime differ from never-disordered daughters of never-disordered mothers in their processing of facial expressions of emotion.Following a negative mood induction, daughters completed an emotion identification task in which they watched faces slowly change from a neutral to a full-intensity happy, sad, or angry expression. We assessed both the intensity that was required to accurately identify the emotion being expressed and errors in emotion identification.Daughters of depressed mothers required greater intensity than did daughters of control mothers to accurately identify sad facial expressions; they also made significantly more errors identifying angry expressions.Cognitive biases may increase vulnerability for the onset of disorders and should be considered in early intervention and prevention efforts.

  View details for DOI 10.1111/j.1469-7610.2009.02175.x

  View details for Web of Science ID 000276246900006

  View details for PubMedID 19788553

  View details for PubMedCentralID PMC2862827

• Prefrontal Grey Matter Volume Abnormalities in Adolescent First Episode Mania 65th Annual Convention of the Society-of-Biological-Psychiatry Singh, M. K., Chang, K. D., Reiss, A. L., Gotlib, I. H. ELSEVIER SCIENCE INC. 2010: 222S–223S

  View details for Web of Science ID 000277064200704

• Specificity of cognitive biases in patients with current depression and remitted depression and in patients with asthma PSYCHOLOGICAL MEDICINE Fritzsche, A., Dahme, B., Gotlib, I. H., Joormann, J., MAGNUSSEN, H., Watz, H., Nutzinger, D. O., von Leupoldt, A. 2010; 40 (5): 815-826

  Abstract

  Previous studies have demonstrated a specific cognitive bias for sad stimuli in currently depressed patients; little is known, however, about whether this bias persists after recovery from the depressive episode. Depression is frequently observed in patients with asthma and is associated with a worse course of the disease. Given these high rates of co-morbidity, we could expect to observe a similar bias towards sad stimuli in patients with asthma.We therefore examined cognitive biases in memory and attention in 20 currently and 20 formerly depressed participants, 20 never-depressed patients diagnosed with asthma, and 20 healthy control participants. All participants completed three cognitive tasks: the self-referential encoding and incidental recall task, the emotion face dot-probe task and the emotional Stroop task.Compared with healthy participants, currently and formerly depressed participants, but not patients with asthma, exhibited specific biases for sad stimuli.These results suggest that cognitive biases are evident in depression even after recovery from an acute episode but are not found in never-depressed patients with asthma.

  View details for DOI 10.1017/S0033291709990948

  View details for Web of Science ID 000277324500015

  View details for PubMedID 19719897

• Cardiovascular and affective recovery from anticipatory threat BIOLOGICAL PSYCHOLOGY Waugh, C. E., Panage, S., Mendes, W. B., Gotlib, I. H. 2010; 84 (2): 169-175

  Abstract

  Anticipating a stressor elicits robust cardiovascular and affective responses. Despite the possibility that recovery from these responses may have implications for physical and mental well-being, little research has examined this issue. In this study, participants either gave a public speech or anticipated giving a speech. Compared with speech-givers, participants who anticipated giving a speech, on average, exhibited similar cardiovascular recovery (decreased heart rate [HR] and increased respiratory sinus arrhythmia [RSA]), and reported lower negative affect during recovery. Only in the anticipation condition, however, were cardiovascular recovery and affective recovery associated: poor affective recovery predicted incomplete HR recovery and decreased RSA. These are the first data to compare explicitly recovery from anticipation of a stressor with recovery from the stressor itself. These findings suggest that failing to recover from anticipation has unique physiological costs that, in turn, may contribute to mental and physical illness.

  View details for DOI 10.1016/j.biopsycho.2010.01.010

  View details for Web of Science ID 000279197500002

  View details for PubMedID 20096747

  View details for PubMedCentralID PMC2875335

• Neural Processing of Reward and Loss in Girls at Risk for Major Depression ARCHIVES OF GENERAL PSYCHIATRY Gotlib, I. H., Hamilton, J. P., Cooney, R. E., Singh, M. K., Henry, M. L., Joormann, J. 2010; 67 (4): 380-387

  Abstract

  Deficits in reward processing and their neural correlates have been associated with major depression. However, it is unclear if these deficits precede the onset of depression or are a consequence of this disorder.To determine whether anomalous neural processing of reward characterizes children at familial risk for depression in the absence of a personal history of diagnosable disorder.Comparison of neural activity among children at low and high risk for depression as they process reward and loss.University functional magnetic resonance imaging facility.Thirteen 10- to 14-year-old never-disordered daughters of mothers with recurrent depression ("high risk") and 13 age-matched never-disordered daughters with no family history of depression ("low risk"). Main Outcome Measure Neural activity, as measured using functional magnetic resonance imaging, in key reward and attention neural circuitry during anticipation and receipt of reward and loss.While anticipating gains, high-risk participants showed less activation than did their low-risk counterparts in the putamen and left insula but showed greater activation in the right insula. When receiving punishment, high-risk participants showed greater activation in the dorsal anterior cingulate gyrus than did low-risk participants, who showed greater activation in the caudate and putamen.Familial risk for depression affects neural mechanisms underlying the processing of reward and loss; young girls at risk for depression exhibit anomalies in the processing of reward and loss before the onset of depressive symptoms. Longitudinal studies are needed to examine whether these characteristics predict the subsequent onset of depression.

  View details for PubMedID 20368513

• Further Evidence for the Cultural Norm Hypothesis: Positive Emotion in Depressed and Control European American and Asian American Women CULTURAL DIVERSITY & ETHNIC MINORITY PSYCHOLOGY Chentsova-Dutton, Y. E., Tsai, J. L., Gotlib, I. H. 2010; 16 (2): 284-295

  Abstract

  How does culture shape the effects of depression on emotion? A previous study showed that depression dampened negative emotional responses in European Americans, but increased these responses in Asian Americans (Chentsova-Dutton et al., 2007). These findings support the cultural norm hypothesis, which predicts that depression reduces individuals' abilities to react in culturally ideal ways (i.e., disrupting European Americans' abilities to express emotions openly and Asian Americans' abilities to moderate emotions). In the present study, we examined the generalizability of this hypothesis to positive emotion. We measured the emotional reactivity of 35 European Americans (17 depressed) and 31 Asian Americans (15 depressed) to an amusing film. Consistent with the cultural norm hypothesis, European Americans who were depressed showed dampened emotional reactivity (i.e., fewer smiles, less intense reports of positive emotion, lower cardiac activation) compared to control European Americans, whereas Asian Americans who were depressed showed similar (for smiles and reports of positive emotion), and even greater (for higher cardiac activation) emotional reactivity compared to control Asian Americans. These findings suggest that the cultural norm hypothesis generalizes to positive emotion.

  View details for DOI 10.1037/a0017562

  View details for Web of Science ID 000277174200021

  View details for PubMedID 20438167

  View details for PubMedCentralID PMC2864927

• BDNF Genotype Moderates the Relation Between Physical Activity and Depressive Symptoms HEALTH PSYCHOLOGY Mata, J., Thompson, R. J., Gotlib, I. H. 2010; 29 (2): 130-133

  Abstract

  To test whether the BDNF gene interacts with exercise to predict depressive symptoms. Physical activity is associated with a range of positive health outcomes, including fewer depressive symptoms. One plausible mechanism underlying these findings involves Brain-Derived Neurotrophic Factor (BDNF), a protein hypothesized to limit or repair the damage caused by stress. Physical activity increases expression of BDNF, which may enhance brain health. BDNF expression is controlled by the BDNF gene. Compared with individuals without a BDNF met allele, met-allele carriers have a lower expression of BDNF, which has been associated with Major Depressive Disorder.Eighty-two healthy adolescent girls were genotyped for the BDNF val66met polymorphism, and their depressive symptoms and physical activity were assessed using questionnaires.BDNF genotype, Children's Depression Inventory, and the Physical Activity Questionnaire for Older Children and Adolescents.The BDNF polymorphism was found to moderate the relation between exercise and depressive symptoms: being physically active was protective for girls with a BDNF met allele (fewer depressive symptoms) but not for girls with the val/val polymorphism.By integrating psychological and biological factors, the present study enhances our understanding of how physical activity contributes to resilience to psychopathology.

  View details for DOI 10.1037/a0017261

  View details for Web of Science ID 000276135800005

  View details for PubMedID 20230085

  View details for PubMedCentralID PMC2847262

• Interference resolution in major depression COGNITIVE AFFECTIVE & BEHAVIORAL NEUROSCIENCE Joormann, J., Nee, D. E., Berman, M. G., Jonides, J., Gotlib, I. H. 2010; 10 (1): 21-33

  Abstract

  In two experiments, we investigated individual differences in the ability to resolve interference in participants diagnosed with major depressive disorder (MDD). Participants were administered the "Ignore/Suppress" task, a short-term memory task composed of two steps. In Step 1 ("ignore"), participants were instructed to memorize a set of stimuli while ignoring simultaneously presented irrelevant material. In Step 2 ("suppress"), participants were instructed to forget a subset of the previously memorized material. The ability to resolve interference was indexed by response latencies on two recognition tasks in which participants decided whether a probe was a member of the target set. In Step 1, we compared response latencies to probes from the to-be-ignored list with response latencies to nonrecently presented items. In Step 2, we compared response latencies to probes from the to-be-suppressed list with response latencies to nonrecently presented items. The results indicate that, compared with control participants, depressed participants exhibited increased interference in the "suppress" but not in the "ignore" step of the task, when the stimuli were negative words. No group differences were obtained when we presented letters instead of emotional words. These findings indicate that depression is associated with difficulty in removing irrelevant negative material from short-term memory.

  View details for DOI 10.3758/CABN.10.1.21

  View details for Web of Science ID 000282066600003

  View details for PubMedID 20233953

  View details for PubMedCentralID PMC2845922

• Decreased Hippocampal Volume in Healthy Girls at Risk of Depression ARCHIVES OF GENERAL PSYCHIATRY Chen, M. C., Hamilton, J. P., Gotlib, I. H. 2010; 67 (3): 270-276

  Abstract

  Researchers have documented that the hippocampus is smaller in individuals with depression than in those without. The temporal or causal association of this reduction in hippocampal volume in depression, however, is not known.To test the hypothesis that reduced hippocampal volume precedes and therefore may be implicated in the onset of depression.We used magnetic resonance imaging to examine brain structure volume in individuals at high and low familial risk of depression. Anatomic images from magnetic resonance imaging were analyzed using both whole-brain voxel-based morphometry and manual tracing of the bilateral hippocampus.A research university.Fifty-five girls aged between 9 and 15 years: 23 daughters of mothers with recurrent episodes of depression in the daughter's lifetime (high risk) and 32 age-matched daughters of mothers with no history of psychopathology (low risk). None of the girls had any past or current Axis I psychopathology.Group differences in voxel-based morphometry brain matter density estimates and traced hippocampal volume.Voxel-based morphometry analyses indicated that individuals at high risk of depression had significantly less gray matter density in clusters in the bilateral hippocampus (P < .001) than low-risk participants. Tracing yielded a volumetric reduction in the left hippocampus in the high-risk participants (P < .05).Compared with individuals at low familial risk of the development of depression, high-risk individuals have reduced hippocampal volume, indicating that neuroanatomic anomalies associated with depression may precede the onset of a depressive episode and influence the development and course of this disorder.

  View details for PubMedID 20194827

• 5-HTTLPR moderates the effect of relational peer victimization on depressive symptoms in adolescent girls JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY Benjet, C., Thompson, R. J., Gotlib, I. H. 2010; 51 (2): 173-179

  Abstract

  Relational peer victimization is associated with internalizing symptoms. Compared to boys, girls are more likely to be both relationally victimized by peers and distressed by the victimization. While previous studies have reported that a functional polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR) moderates the effect of stressful life events on depressive symptoms, the present study is the first to evaluate the interaction of this polymorphism with relational peer victimization to predict level of depressive symptoms in young girls.Participants were 78 girls ages 10 to 14 who had no current or past Axis I disorder. Girls were genotyped for 5-HTTLPR; peer victimization was assessed with the Social Experiences Questionnaire, and depressive symptoms with the Children's Depression Inventory.The 5-HTTLPR polymorphism alone did not predict level of depressive symptoms; the interaction of 5-HTTLPR and relational peer victimization, however, was a significant predictor of depressive symptoms. Follow-up analyses indicated that peer victimization significantly predicted level of depressive symptoms only for girls who were homozygous for the short allele, and not for girls homozygous for the long allele or who were heterozygous for the short and long alleles.The findings support the diathesis-stress model of depression: having two 5-HTTLPR short alleles confers vulnerability to depressive symptoms in adolescent girls when they experience relational peer victimization. These findings also suggest that relational peer victimization, at least for girls with genetic vulnerability, is a significant source of stress and should be recognized in the monitoring and prevention of bullying.

  View details for DOI 10.1111/j.1469-7610.2009.02149.x

  View details for Web of Science ID 000273310800007

  View details for PubMedID 19754661

  View details for PubMedCentralID PMC2804775

• Neural correlates of inhibitory deficits in depression PSYCHIATRY RESEARCH-NEUROIMAGING Eugene, F., Joormann, J., Cooney, R. E., Atlas, L. Y., Gotlib, I. H. 2010; 181 (1): 30-35

  Abstract

  The present study used functional magnetic resonance imaging to examine neural correlates of inhibitory dysfunction in individuals diagnosed with major depressive disorder (MDD). Twelve MDD participants and 12 never-depressed controls completed the negative affective priming (NAP) task in the scanner. Results indicated that, in depressed participants, increased activation in the rostral anterior cingulate cortex (rACC) is associated with inhibition of negative, but not positive, words; in contrast, in nondepressed participants, inhibition of positive, but not negative, words is associated with increased activation in the rACC. These findings indicate that abnormalities in neural function, especially in the rACC, may underlie difficulties experienced by depressed individuals in inhibiting negative thoughts. These results underscore the importance of continuing to examine the relation between cognitive and neural functioning in depression in order to gain a broader and more integrative understanding of this disorder.

  View details for DOI 10.1016/j.pscychresns.2009.07.010

  View details for Web of Science ID 000274423000005

  View details for PubMedID 19962859

  View details for PubMedCentralID PMC2795107

• The neural temporal dynamics of the intensity of emotional experience NEUROIMAGE Waugh, C. E., Hamilton, J. P., Gotlib, I. H. 2010; 49 (2): 1699-1707

  Abstract

  Despite the fact that emotions involve multiple time-varying components, little is known about the underlying neural basis of these temporal dynamics. In this paper, we assess these temporal dynamics by using time-varying hemodynamic response functions (HRF) to model BOLD responses to emotional stimuli. We show that these time-varying HRFs lead to a better fit to the BOLD data and yield larger areas of significant activation than do conventional gamma-based canonical HRFs. We also report for the first time that intensity of emotional experience is associated with both magnitude and duration of brain activation. Specifically, greater negative emotional intensity was associated with greater magnitude of activation in the occipital cortex and with longer duration of activation in regions along the cortical midline associated with self-referent processing: the anterior medial prefrontal cortex and the posterior cingulate cortex. These data significantly advance our understanding of how the brain processes emotion and suggest that the intensity of a negative emotional experience is due in part to elaborative self-referent processing that is captured by the duration of neural activity in cortical midline structures. These data also underscore the importance of using modeling techniques that will help elucidate the chronometry of both normal and psychopathological emotional processes.

  View details for DOI 10.1016/j.neuroimage.2009.10.006

  View details for Web of Science ID 000272808400053

  View details for PubMedID 19833213

  View details for PubMedCentralID PMC2794551

• Emotion regulation in depression: Relation to cognitive inhibition COGNITION & EMOTION Joormann, J., Gotlib, I. H. 2010; 24 (2): 281-298

  Abstract

  Depression is a disorder of impaired emotion regulation. Consequently, examining individual differences in the habitual use of emotion regulation strategies has considerable potential to inform models of this debilitating disorder. The aim of the current study was to identify cognitive processes that may be associated with the use of emotion regulation strategies and to elucidate their relation to depression. Depression has been found to be associated with difficulties in cognitive control and, more specifically, with difficulties inhibiting the processing of negative material. We used a negative affective priming task to assess the relations among inhibition and individual differences in the habitual use of rumination, reappraisal, and expressive suppression in clinically depressed, formerly depressed, and never-depressed participants. We found that depressed participants exhibited the predicted lack of inhibition when processing negative material. Moreover, within the group of depressed participants, reduced inhibition of negative material was associated with greater rumination. Across the entire sample, reduced inhibition of negative material was related to less use of reappraisal and more use of expressive suppression. Finally, within the formerly depressed group, less use of reappraisal, more use of rumination, and greater expressive suppression were related to higher levels of depressive symptoms. These findings suggest that individual differences in the use of emotion regulation strategies play an important role in depression, and that deficits in cognitive control are related to the use of maladaptive emotion regulation strategies in this disorder.

  View details for DOI 10.1080/02699930903407948

  View details for Web of Science ID 000274980700007

  View details for PubMedID 20300538

  View details for PubMedCentralID PMC2839199

• FLEXIBLE AFFECTIVE AND PHYSIOLOGICAL RESPONSIVENESS IN TRAIT RESILIENCE Waugh, C. E., Thompson, R. J., Bhattacharjee, K., Gotlib, I. H. WILEY-BLACKWELL PUBLISHING, INC. 2010: S31–S32

  View details for Web of Science ID 000280662000175

• THE RELATION BETWEEN INTEROCEPTIVE AWARENESS AND DECISION-MAKING DIFFICULTIES IN MAJOR DEPRESSIVE DISORDER Bhattacharjee, K., Furman, D. J., Gotlib, I. H. WILEY-BLACKWELL PUBLISHING, INC. 2010: S32

  View details for Web of Science ID 000280662000176

• Cognition and Depression: Current Status and Future Directions ANNUAL REVIEW OF CLINICAL PSYCHOLOGY, VOL 6 Gotlib, I. H., Joormann, J. 2010; 6: 285-312

  Abstract

  Cognitive theories of depression posit that people's thoughts, inferences, attitudes, and interpretations, and the way in which they attend to and recall information, can increase their risk for depression. Three mechanisms have been implicated in the relation between biased cognitive processing and the dysregulation of emotion in depression: inhibitory processes and deficits in working memory, ruminative responses to negative mood states and negative life events, and the inability to use positive and rewarding stimuli to regulate negative mood. In this review, we present a contemporary characterization of depressive cognition and discuss how different cognitive processes are related not only to each other, but also to emotion dysregulation, the hallmark feature of depression. We conclude that depression is characterized by increased elaboration of negative information, by difficulties disengaging from negative material, and by deficits in cognitive control when processing negative information. We discuss treatment implications of these conclusions and argue that the study of cognitive aspects of depression must be broadened by investigating neural and genetic factors that are related to cognitive dysfunction in this disorder. Such integrative investigations should help us gain a more comprehensive understanding of how cognitive and biological factors interact to affect the onset, maintenance, and course of depression.

  View details for DOI 10.1146/annurev.clinpsy.121208.131305

  View details for Web of Science ID 000277906700012

  View details for PubMedID 20192795

  View details for PubMedCentralID PMC2845726

• BDNF genotype modulates resting functional connectivity in children FRONTIERS IN HUMAN NEUROSCIENCE Thomason, M. E., Yoo, D. J., Glover, G. H., Gotlib, I. H. 2009; 3

  Abstract

  A specific polymorphism of the brain-derived neurotrophic factor (BDNF) gene is associated with alterations in brain anatomy and memory; its relevance to the functional connectivity of brain networks, however, is unclear. Given that altered hippocampal function and structure has been found in adults who carry the methionine (met) allele of the BDNF gene and the molecular studies elucidating the role of BDNF in neurogenesis and synapse formation, we examined the association between BDNF gene variants and neural resting connectivity in children and adolescents. We observed a reduction in hippocampal and parahippocampal to cortical connectivity in met-allele carriers within both default-mode and executive networks. In contrast, we observed increased connectivity to amygdala, insula and striatal regions in met-carriers, within the paralimbic network. Because of the known association between the BDNF gene and neuropsychiatric disorder, this latter finding of greater connectivity in circuits important for emotion processing may indicate a new neural mechanism through which these gene-related psychiatric differences are manifest. Here we show that the BDNF gene, known to regulate synaptic plasticity and connectivity in the brain, affects functional connectivity at the neural systems level. In addition, we demonstrate that the spatial topography of multiple high-level resting state networks in healthy children and adolescents is similar to that observed in adults.

  View details for DOI 10.3389/neuro.09.055.2009

  View details for Web of Science ID 000274619300004

  View details for PubMedID 19956404

  View details for PubMedCentralID PMC2786303

• Rumination and Impaired Resource Allocation in Depression JOURNAL OF ABNORMAL PSYCHOLOGY Levens, S. M., Muhtadie, L., Gotlib, I. H. 2009; 118 (4): 757-766

  Abstract

  Depression is characterized by a range of cognitive deficits that theorists posit are due to the resource capturing properties of rumination. The present study was designed to examine the relation between rumination and resource allocation in depression. Twenty-five depressed and 25 nondepressed participants completed a modified dual-task version of the recency-probes task, which assesses the controlled allocation of cognitive resources by comparing performance across low- and high-interference conditions. In low-interference conditions, participants performed either the recency-probes task or a tracking task, which required participants to track specific stimuli across trials (i.e., no dual-task interference). In the high-interference condition, participants performed both the recency-probes task and the tracking task, which required the controlled allocation of resources to resolve dual-task interference. Depressed participants performed significantly worse than did their nondepressed counterparts in only the high-interference condition; performance of the 2 groups was comparable in the low-interference conditions. Furthermore, the degree to which depressed participants were impaired in the high-interference condition was correlated .74 with rumination. These findings suggest that an association between rumination and impairments in resource allocation underlies the cognitive difficulties experienced by depressed individuals.

  View details for DOI 10.1037/a0017206

  View details for Web of Science ID 000271669100007

  View details for PubMedID 19899845

  View details for PubMedCentralID PMC2836938

• Identification of Emotional Facial Expressions Following Recovery From Depression JOURNAL OF ABNORMAL PSYCHOLOGY LeMoult, J., Joormann, J., Sherdell, L., Wright, Y., Gotlib, I. H. 2009; 118 (4): 828-833

  Abstract

  This study investigated the identification of facial expressions of emotion in currently nondepressed participants who had a history of recurrent depressive episodes (recurrent major depression; RMD) and never-depressed control participants (CTL). Following a negative mood induction, participants were presented with faces whose expressions slowly changed from neutral to full intensity. Identification of facial expressions was measured by the intensity of the expression at which participants could accurately identify whether faces expressed happiness, sadness, or anger. There were no group differences in the identification of sad or angry expressions. Compared with CTL participants, however, RMD participants required significantly greater emotional intensity in the faces to correctly identify happy expressions. These results indicate that biases in the processing of emotional facial expressions are evident even after individuals have recovered from a depressive episode.

  View details for DOI 10.1037/a0016944

  View details for Web of Science ID 000271669100014

  View details for PubMedID 19899852

  View details for PubMedCentralID PMC2837802

• COMT genotype and resting brain perfusion in children NEUROIMAGE Thomason, M. E., Waugh, C. E., Glover, G. H., Gotlib, I. H. 2009; 48 (1): 217-222

  Abstract

  Levels of extra-synaptic dopamine in the brain vary as a function of polymorphisms at the val158met locus of the catechol-O-methyltransferase (COMT) gene. In vivo studies of this polymorphism in the human brain have typically measured patterns of neural activation during dopamine-mediated tasks in adults. This study is the first to investigate the effects of COMT on brain physiology during rest and in children. We used flow-sensitive arterial spin-labeling (ASL) magnetic resonance imaging to examine brain blood flow (CBF) in 42 children. Compared with val-allele carriers, met-allele homozygotes exhibited greater CBF in mesolimbic, mesocortical, and nigrostriatal dopamine (DA) pathways. Higher CBF in DA-rich brain structures reflects COMT-related baseline differences that (1) underlie the selective behavioral advantages associated with each genotype; (2) affect interpretations of previously reported genotype differences in BOLD signal changes; and (3) serve as a foundation for future studies on the effects of COMT on brain development.

  View details for DOI 10.1016/j.neuroimage.2009.05.076

  View details for Web of Science ID 000269321100025

  View details for PubMedID 19500679

  View details for PubMedCentralID PMC2735191

• Selective Attention to Emotion in the Aging Brain PSYCHOLOGY AND AGING Samanez-Larkin, G. R., Robertson, E. R., Mikels, J. A., Carstensen, L. L., Gotlib, I. H. 2009; 24 (3): 519-529

  Abstract

  A growing body of research suggests that the ability to regulate emotion remains stable or improves across the adult life span. Socioemotional selectivity theory maintains that this pattern of findings reflects the prioritization of emotional goals. Given that goal-directed behavior requires attentional control, the present study was designed to investigate age differences in selective attention to emotional lexical stimuli under conditions of emotional interference. Both neural and behavioral measures were obtained during an experiment in which participants completed a flanker task that required them to make categorical judgments about emotional and nonemotional stimuli. Older adults showed interference in both the behavioral and neural measures on control trials but not on emotion trials. Although older adults typically show relatively high levels of interference and reduced cognitive control during nonemotional tasks, they appear to be able to successfully reduce interference during emotional tasks.

  View details for DOI 10.1037/a0016952

  View details for Web of Science ID 000269933600001

  View details for PubMedID 19739908

  View details for PubMedCentralID PMC2791508

• Association Between the Catechol-O-Methyltransferase Val158Met Polymorphism and Self-Perceived Social Acceptance in Adolescent Girls JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY Waugh, C. E., Dearing, K. F., Joormann, J., Gotlib, I. H. 2009; 19 (4): 395-401

  Abstract

  Low perceived social acceptance is a significant risk factor for emotional difficulties in children. No studies, however, have examined genetic factors that may underlie individual differences in perceived social acceptance. In the present study we examined the relation between polymorphisms on the catechol-O-methyltransferase (COMT) Val158Met and serotonin transporter promoter (5-HTTLPR) genes and perceived social acceptance in 103 adolescent girls. Only the COMT polymorphism was related to perceived social acceptance: Val-allele carriers reported greater perceived social acceptance than did homozygous Met-allele carriers. In a subsample of these participants, homozygous Val-allele carriers reported greater maintenance of positive emotions during stress. This, in turn, predicted social acceptance, suggesting that COMT exerts its effects on social functioning through emotion regulation. These data are the first to show an association between COMT and social functioning in children. Future research might profitably examine emotion regulation as a mediator between COMT and social acceptance.

  View details for DOI 10.1089/cap.2008.0141

  View details for Web of Science ID 000269231100007

  View details for PubMedID 19702491

  View details for PubMedCentralID PMC2830202

• Discovering Neural Primacy in Depression: Granger Causality Analysis of Resting State BOLD Data (vol 65, pg 234S, 2009) BIOLOGICAL PSYCHIATRY Hamilton, J., Chen, G., Thomason, M. E., Johnson, R. F., Gotlib, I. H. 2009; 66 (3): 302

  View details for DOI 10.1016/j.biopysch.2009.06.001

  View details for Web of Science ID 000267961600017

• Serotonin transporter polymorphism predicts waking cortisol in young girls PSYCHONEUROENDOCRINOLOGY Chen, M. C., Joormann, J., Hallmayer, J., Gotlib, I. H. 2009; 34 (5): 681-686

  Abstract

  Major Depressive Disorder (MDD) is one of the most prevalent and costly of all psychiatric disorders. The hypothalamic pituitary adrenal (HPA)-axis, which regulates the hormonal response to stress, has been found to be disrupted in depression. HPA dysregulation may represent an important risk factor for depression. To examine a possible genetic underpinning of this risk factor without the confound of current or lifetime depression, we genotyped 84 never-disordered young girls, over a third of whom were at elevated risk for depression, to assess the association between a polymorphism in the promoter region of the serotonin transporter (5-HTT) gene and diurnal variation in HPA-axis activity. This 5-HTT-linked polymorphic region (5-HTTLPR) has been previously found to interact with stress to increase risk for depression. We found 5-HTTLPR to be significantly associated with diurnal cortisol levels: girls who were homozygous for the short-allele had higher levels of waking (but not afternoon or evening) cortisol than did their long-allele counterparts. This finding suggests that genetic susceptibility to HPA-axis dysregulation, especially apparent in levels of waking cortisol, is detectable in individuals as young as 9 years of age.

  View details for DOI 10.1016/j.psyneuen.2008.11.006

  View details for PubMedID 19128885

• Sadder and Less Accurate? False Memory for Negative Material in Depression JOURNAL OF ABNORMAL PSYCHOLOGY Joormann, J., Teachman, B. A., Gotlib, I. H. 2009; 118 (2): 412-417

  Abstract

  Previous research has demonstrated that induced sad mood is associated with increased accuracy of recall in certain memory tasks; the effects of clinical depression, however, are likely to be quite different. The authors used the Deese-Roediger-McDermott paradigm to examine the impact of clinical depression on erroneous recall of neutral and/or emotional stimuli. Specifically, they presented Deese-Roediger-McDermott lists that were highly associated with negative, neutral, or positive lures and compared participants diagnosed with major depressive disorder and nondepressed control participants on the accuracy of their recall of presented material and their false recall of never-presented lures. Compared with control participants, major depressive disorder participants recalled fewer words that had been previously presented but were more likely to falsely recall negative lures; there were no differences between major depressive disorder and control participants in false recall of positive or neutral lures. These findings indicate that depression is associated with false memories of negative material.

  View details for DOI 10.1037/a0015621

  View details for Web of Science ID 000265893300015

  View details for PubMedID 19413415

  View details for PubMedCentralID PMC3292784

• IMPAIRED SELECTION OF RELEVANT POSITIVE INFORMATION IN DEPRESSION DEPRESSION AND ANXIETY Levens, S. M., Gotlib, I. H. 2009; 26 (5): 403-410

  Abstract

  A hallmark characteristic of depression is the inability to regulate the effect of emotional material on cognition. Previous research has demonstrated that depressed individuals are less able than are nondepressed persons to expel irrelevant negative information from working memory (WM), thereby exacerbating the effects of negative content on cognition. The primary goal of this study was to examine whether depressed individuals are also impaired at selecting relevant positive content in the context of representations competing for resources in WM; such an impairment would limit depressed persons' ability to use positive material to ameliorate the cognitive effects of negative information.We administered a Recency-probes task with neutral, positive, and negative words to 20 currently depressed and 22 never-depressed participants. This task assesses the selection of relevant content in WM by inducing interference between current and prior representations of a stimulus in WM. Reaction times to interference and noninterference trials were compared across valence and group to assess how effectively depressed individuals select task-relevant emotional content to resolve interference.Compared to never-depressed controls, depressed individuals were impaired in selecting task-relevant positive stimuli; the performance of the two groups was comparable for selecting task-relevant neutral and negative stimuli.Findings indicate that a valence-specific deficit in WM may contribute to the inability of depressed individuals to regulate emotion, and provide empirical support for formulations that implicate positive insensitivity in the maintenance of depression.

  View details for DOI 10.1002/da.20565

  View details for Web of Science ID 000265874300003

  View details for PubMedID 19347861

  View details for PubMedCentralID PMC2836936

• COMT Genotype and Resting Brain Perfusion in Children 64th Annual Convention of the Society-of-Biological-Psychiatry Thomason, M. E., Waugh, C. E., Glover, G. H., Gotlib, I. H. ELSEVIER SCIENCE INC. 2009: 7S–7S

  View details for Web of Science ID 000265144200020

• Deficient Amygdala Responsivity to Positive Content May Underlie Positive Insensitivity in Depression: A Lesion Study Levens, S. M., Devinsky, O., Phelps, E. A., Gotlib, I. H. ELSEVIER SCIENCE INC. 2009: 34S–35S

  View details for Web of Science ID 000265144200108

• Neural Substrates of Attentional Capture by Negative Information in Social Phobia Schwartz, M. E., Hamilton, J., Gotlib, I. H. ELSEVIER SCIENCE INC. 2009: 122S

  View details for Web of Science ID 000265144200394

• Discovering Neural Primacy in Depression: Granger Causality Analysis of Resting State BOLD Data Hamilton, J., Chen, G., Thomason, M. E., Gotlib, I. H. ELSEVIER SCIENCE INC. 2009: 234S

  View details for Web of Science ID 000265144200742

• Response of Viscero-Affective Brain Regions to Remembered Negative Material Predicts Poorer Outcome in Major Depression 64th Annual Convention of the Society-of-Biological-Psychiatry Hamilton, J. P., Sherdell, L., Gotlib, I. H. ELSEVIER SCIENCE INC. 2009: 19S–19S

  View details for Web of Science ID 000265144200056

• Stressful Life Events, Chronic Difficulties, and the Symptoms of Clinical Depression JOURNAL OF NERVOUS AND MENTAL DISEASE Muscatell, K. A., Slavich, G. M., Monroe, S. M., Gotlib, I. H. 2009; 197 (3): 154-160

  Abstract

  Major life events and chronic difficulties have been found to be associated with the onset of depression. Little is known, however, about how exposure to such stressors is related to the clinical presentation of this disorder. We addressed this issue by administering an interview-based measure of life stress, the Beck Depression Inventory, and the Global Assessment of Functioning scale to 100 adults diagnosed with major depressive disorder. Participants who experienced a preonset severe life event exhibited greater overall levels of depression severity, endorsed more cognitive and somatic symptoms of depression, and functioned at lower levels than did their counterparts without preonset severe life events. In contrast, exposure to a preonset severe difficulty was unrelated to participants' severity of depression, cognitive and somatic symptoms, or level of global functioning. These findings highlight the potentially greater importance of acute stress compared with chronic stress for influencing these key clinical features of depression.

  View details for DOI 10.1097/NMD.0b013e318199f77b

  View details for Web of Science ID 000264263300002

  View details for PubMedID 19282680

  View details for PubMedCentralID PMC2840389

• Training Forgetting of Negative Material in Depression JOURNAL OF ABNORMAL PSYCHOLOGY Joormann, J., Hertel, P. T., LeMoult, J., Gotlib, I. H. 2009; 118 (1): 34-43

  Abstract

  In this study, the authors investigated whether training participants to use cognitive strategies can aid forgetting in depression. Participants diagnosed with major depressive disorder (MDD) and never-depressed participants learned to associate neutral cue words with a positive or negative target word and were then instructed not to think about the negative targets when shown their cues. The authors compared 3 different conditions: an unaided condition, a positive-substitute condition, and a negative-substitute condition. In the substitute conditions, participants were instructed to use new targets to keep from thinking about the original targets. After the training phase, participants were instructed to recall all targets when presented with the cues. MDD participants, in contrast with control participants, did not exhibit forgetting of negative words in the unaided condition. In both the negative and positive substitute conditions, however, MDD participants showed successful forgetting of negative words and a clear practice effect. In contrast, negative substitute words did not aid forgetting by the control participants. These findings suggest that training depressed individuals to use cognitive strategies can increase forgetting of negative words.

  View details for DOI 10.1037/a0013794

  View details for Web of Science ID 000263369700005

  View details for PubMedID 19222312

  View details for PubMedCentralID PMC2836940

• Judging the Intensity of Facial Expressions of Emotion: Depression-Related Biases in the Processing of Positive Affect JOURNAL OF ABNORMAL PSYCHOLOGY Yoon, K. L., Joormann, J., Gotlib, I. H. 2009; 118 (1): 223-228

  Abstract

  A forced-choice intensity judgment task was used to investigate biases in the processing of subtle expressions of emotion in participants with major depressive disorder (MDD). Participants were presented with 2 pictures of the same actor side by side, either depicting a neutral and a subtle emotional expression or depicting a subtle positive and a subtle negative expression. Participants were asked to indicate which of the 2 pictures showed the stronger emotion. Compared with participants with social anxiety disorder (SAD) and with never-disordered controls (CTLs), participants with MDD were less likely to judge subtle happy expressions as more intense than neutral expressions. In addition, compared with the CTL participants, participants who had MDD and participants who had SAD were less likely to judge subtle happy expressions to be more intense than negative expressions. Biases in the judgment of the intensity of subtle expressions of positive affect could play an important role in the interpersonal difficulties that are associated with depression.

  View details for DOI 10.1037/a0014658

  View details for Web of Science ID 000263369700021

  View details for PubMedID 19222328

  View details for PubMedCentralID PMC2835523

• TARGETED REJECTION PREDICTS HASTENED ONSET OF MAJOR DEPRESSION JOURNAL OF SOCIAL AND CLINICAL PSYCHOLOGY Slavich, G. M., Thornton, T., Torres, L. D., Monroe, S. M., Gotlib, I. H. 2009; 28 (2): 223-243

  Abstract

  Although severe life stress frequently precipitates the onset of major depression, little is known about the basic nature of stressors in this general category of adversity and how exposure to different life events might be related to clinical aspects of the disorder. We addressed this issue by introducing, and examining the effects of, targeted rejection (TR), which involves the exclusive, active, and intentional social rejection of an individual by others. Twenty-seven adults with major depressive disorder were administered an interview-based measure of life stress. Severe life events that occurred prior to the onset of depression were subsequently coded as TR or as non-TR. Participants who experienced a pre-onset severe TR event became depressed approximately three times faster than did their non-TR counterparts. These findings highlight the potential importance of TR as a marker of hastened depression onset and demonstrate how refining characterizations of stress may advance our understanding of depression.

  View details for Web of Science ID 000263610700004

  View details for PubMedCentralID PMC2847269

• Interpretation of Ambiguous Information in Girls at Risk for Depression JOURNAL OF ABNORMAL CHILD PSYCHOLOGY Dearing, K. F., Gotlib, I. H. 2009; 37 (1): 79-91

  Abstract

  Research has consistently documented that depressed individuals process information in a negatively biased manner. There is little evidence, however, concerning whether these biases represent risk factors for depression, as is hypothesized by cognitive models. In the present study we investigated whether a particular cognitive bias observed in currently depressed individuals, the tendency to interpret ambiguous information negatively, characterizes daughters of depressed mothers, a population known to be at increased risk for depression. Following a negative mood induction, young daughters of depressed and never-disordered mothers completed two information-processing tasks in which their interpretations of emotionally ambiguous stimuli were evaluated. Daughters of depressed mothers interpreted ambiguous words more negatively and less positively, and ambiguous stories more negatively, than did daughters of never-disordered mothers. These results provide support for cognitive vulnerability models of depression.

  View details for DOI 10.1007/s10802-008-9259-z

  View details for Web of Science ID 000262672800006

  View details for PubMedID 18679791

  View details for PubMedCentralID PMC2836928

• Parental Depression: Impact on Offspring and Mechanisms Underlying Transmission of Risk HANDBOOK OF DEPRESSION IN ADOLESCENTS Joormann, J., Eugene, F., Gotlib, I. H., NolenHoeksema, S., Hilt, L. M. 2009: 441–72

  View details for Web of Science ID 000333146100017

• Neurobiology of emotion regulation in children and adults NEUROIMAGING IN DEVELOPMENTAL CLINICAL NEUROSCIENCE Gotlib, I. H., Joormann, J., Rumsey, J. M., Ernst, M. 2009: 38–52

  View details for DOI 10.1017/CBO9780511757402.006

  View details for Web of Science ID 000313574600005

• Motivation for reward as a function of required effort: Dissociating the 'liking' from the 'wanting' system in humans MOTIVATION AND EMOTION Waugh, C. E., Gotlib, I. H. 2008; 32 (4): 323-330

  View details for DOI 10.1007/s11031-008-9104-2

  View details for Web of Science ID 000260960500008

• Emotion (Dys)regulation and Links to Depressive Disorders CHILD DEVELOPMENT PERSPECTIVES Kovacs, M., Joormann, J., Gotlib, I. H. 2008; 2 (3): 149-155

  Abstract

  Clinical depression is a significant mental health problem that is associated with personal suffering and impaired functioning. These effects underscore the continuing need for new approaches that can inform researchers and clinicians when designing interventions. We propose that individual differences in the self-regulation of sadness and distress provide an important link between stress, depressed mood, and the onset of depressive disorder, and that if we have a better understanding of the ways children successfully manage negative emotions, we can better prevent and treat pediatric depression. In this article, we therefore examine the normative development of responses that children use to attenuate sadness, and aspects of the neurobiological infrastructure that both enable and constrain such self-regulatory efforts. We also address the emerging literature on affect regulation among children at familial risk for depressive disorders. We conclude that problems with adaptively self-regulating sadness and distress represent one pathway that can lead to juvenile-onset depression. And we need integrated, developmental studies of the psychosocial and neurobiological aspects of self-regulatory responses to sadness and distress in order to better understand this process, and to design age-sensitive intervention strategies for pediatric depression.

  View details for Web of Science ID 000270262600005

  View details for PubMedCentralID PMC2922756

• Reduced caudate gray matter volume in women with major depressive disorder PSYCHIATRY RESEARCH-NEUROIMAGING Kim, A. J., Hamilton, J. P., Gotlib, I. H. 2008; 164 (2): 114-122

  Abstract

  Previous brain-imaging studies have reported that major depressive disorder (MDD) is characterized by decreased volumes of several cortical and subcortical structures, including the hippocampus, amygdala, anterior cingulate cortex, and caudate nucleus. The purpose of the present study was to identify structural volumetric differences between MDD and healthy participants using a method that allows a comparison of gray and white matter volume across the whole brain. In addition, we explored the relation between symptom severity and brain regions with decreased volumes in MDD participants. The study group comprised 22 women diagnosed with MDD and 25 healthy women with no history of major psychiatric disorders. Magnetic resonance brain images were analyzed using optimized voxel-based morphometry to examine group differences in regional gray and white matter volume. Compared with healthy controls, MDD participants were found to have decreased gray matter volume in the bilateral caudate nucleus and the thalamus. No group differences were found for white matter volume, nor were there significant correlations between gray matter volumes and symptom severity within the MDD group. The present results suggest that smaller volume of the caudate nucleus may be related to the pathophysiology of MDD and may account for abnormalities of the cortico-striatal-pallido-thalamic loop in MDD.

  View details for DOI 10.1016/j.pscychresns.2007.12.020

  View details for Web of Science ID 000261551600003

  View details for PubMedID 18930633

  View details for PubMedCentralID PMC2600594

• Amygdala volume in major depressive disorder: a meta-analysis of magnetic resonance imaging studies MOLECULAR PSYCHIATRY Hamilton, J. P., Siemer, M., Gotlib, I. H. 2008; 13 (11): 993-1000

  Abstract

  Major depressive disorder has been associated with volumetric abnormality in the amygdala. In this meta-analysis we examine results from magnetic resonance imaging volumetry studies of the amygdala in depression in order to assess both the nature of the relationship between depression and amygdala volume as well as the influence of extraexperimental factors that may account for significant variability in reported findings. We searched PubMed and ISI Web of Knowledge databases for articles published from 1985 to 2008 that used the wildcard terms 'Depress*' and 'Amygdal*' in the title, keywords or abstract. From the 13 studies that met inclusion criteria for our meta-analysis, we calculated aggregate effect size and heterogeneity estimates from amygdala volumetric data; we then used meta-regression to determine whether variability in specific extraexperimental factors accounted for variability in findings. The lack of a reliable difference in amygdala volume between depressed and never-depressed individuals was accounted for by a positive correlation between amygdala volume differences and the proportion of medicated depressed persons in study samples: whereas the aggregate effect size calculated from studies that included only medicated individuals indicated that amygdala volume was significantly increased in depressed relative to healthy persons, studies with only unmedicated depressed individuals showed a reliable decrease in amygdala volume in depression. These findings are consistent with a formulation in which an antidepressant-mediated increase in levels of brain-derived neurotrophic factor promotes neurogenesis and protects against glucocorticoid toxicity in the amygdala in medicated but not in unmedicated depression.

  View details for DOI 10.1038/mp.2008.57

  View details for Web of Science ID 000260632200002

  View details for PubMedID 18504424

• Default-mode function and task-induced deactivation have overlapping brain substrates in children NEUROIMAGE Thomason, M. E., Chang, C. E., Glover, G. H., Gabrieli, J. D., Greicius, M. D., Gotlib, I. H. 2008; 41 (4): 1493-1503

  Abstract

  The regions that comprise the functionally connected resting-state default-mode network (DMN) in adults appear to be the same as those that are characterized by task-induced decreases in blood-oxygen-level-dependent (BOLD) signal. Independent component analysis can be used to produce a picture of the DMN as an individual rests quietly in the scanner. Contrasts across conditions in which cognitive load is parametrically modulated can delineate neural structures that have decreases in activation in response to high-demand task conditions. Examination of the degree to which these networks subsume dissociable brain substrates, and of the degree to which they overlap, provides insight concerning their purpose, function, and the nature of their associations. Few studies have examined the DMN in children, and none have tested whether the neural regions that comprise the DMN during a resting condition are the same regions that show reduced activity when children engage in cognitive tasks. In this paper we describe regions that show both task-related decreases and spontaneous intrinsic activity at rest in children, and we examine the co-localization of these networks. We describe ways in which the DMN in 7-12-year-old children is both similar to and different from the DMN in adults; moreover, we document that task-induced deactivations and default-mode resting-state activity in children share common neural substrates. It appears, therefore, that even before adolescence a core aspect of task-induced deactivation involves reallocating processing resources that are active at rest. We describe how future studies assessing the development of these systems would benefit from examining these constructs as part of one continuous system.

  View details for DOI 10.1016/j.neuroimage.2008.03.029

  View details for Web of Science ID 000256620400029

  View details for PubMedID 18482851

  View details for PubMedCentralID PMC2735193

• Neural substrates of increased memory sensitivity for negative stimuli in major depression 62nd Annual Meeting of the Society-of-Biological-Psychiatry Hamilton, J. P., Gotlib, I. H. ELSEVIER SCIENCE INC. 2008: 1155–62

  Abstract

  Although memory biases for negatively valenced stimuli have been reliably associated with depression and have been postulated to play a critical role in the maintenance of this disorder, the neural bases of these biases have received little attention. In this study, we tested a model of heightened memory sensitivity for negative information in depression in which neural mechanisms that normally facilitate memory for affective material are over-recruited during encoding of negative material in depression.We used functional magnetic resonance imaging to examine amygdala activity and functional connectivity with the hippocampus and caudate-putamen during successful encoding--as assessed by a recognition memory probe 1 week after scanning--of negative, neutral, and positive pictures by 14 depressed and 12 nondepressed individuals.Depressed individuals demonstrated greater memory sensitivity than nondepressed participants to negative but not to neutral or positive stimuli. The right amygdala was more active and showed greater functional connectivity with the hippocampus and caudate-putamen in depressed than in control participants during encoding of subsequently remembered negative but not neutral or positive stimuli. The degree of memory-related right amygdala responsivity in the depressed participants was significantly correlated with depressive severity.These findings support the formulation that, in remembering negative information better than nondepressed persons, depressed individuals over-recruit a neural network involved more generally in enhancing memory for affective stimuli and that the degree to which they over-recruit this system is related to the severity of clinical symptomatology.

  View details for DOI 10.1016/j.biopsych.2007.12.015

  View details for Web of Science ID 000256491700009

  View details for PubMedID 18281017

  View details for PubMedCentralID PMC2474758

• Specificity of information-processing biases in patients with current and remitted depression and in patients with asthma Fritzsche, A., Dahme, B., Gotlib, I., Joormann, J., Nutzinger, D. O., Watz, H., von Leupoldt, A. PSYCHOLOGY PRESS. 2008: 757

  View details for Web of Science ID 000259264309005

• Genetics, brain imaging and cognitive-emotional aspects and their relevance for psychopathology Joormann, J., Gotlib, I. PSYCHOLOGY PRESS. 2008: 714–15

  View details for Web of Science ID 000259264308413

• Biases in interpretation and memory in Generalized Social Phobia JOURNAL OF ABNORMAL PSYCHOLOGY Hertel, P. T., Brozovich, F., Joormann, J., Gotlib, I. H. 2008; 117 (2): 278-288

  Abstract

  Two experiments examined the link between interpretation and memory in individuals diagnosed with Generalized Social Phobia (GSP). In Experiment 1, GSP and control participants generated continuations for nonsocial and ambiguous social scenarios. GSP participants produced more socially anxious and negative continuations for the social scenarios than did the controls. On the subsequent test of recalling the social scenarios, intrusion errors that shared meaning with the original continuations were made more frequently by the GSP group, producing false recall with emotionally negative features. To examine whether nonanxious individuals would also produce such errors if given emotional interpretations, in Experiment 2 the authors asked university students to read the scenarios plus endings produced by GSP participants in Experiment 1. The students either constructed vivid mental images of themselves as the main characters or thought about whether the endings provided closure. Low-anxious students in the closure condition produced fewer ending-based intrusions in recalling the social scenarios than did students in the other 3 conditions. Results illustrate the importance of examining the nature of source-monitoring errors in investigations of memory biases in social anxiety.

  View details for DOI 10.1037/0021-843X.117.2.278

  View details for Web of Science ID 000255671500003

  View details for PubMedID 18489204

• HPA axis reactivity: A mechanism underlying the associations among 5-HTTLPR, stress, and depression BIOLOGICAL PSYCHIATRY Gotlib, I. H., Joormann, J., Minor, K. L., Hallmayer, J. 2008; 63 (9): 847-851

  Abstract

  Recent evidence indicates that individuals who are homozygous for the short (s) allele in the promoter region of the serotonin transporter gene have higher rates of depression and other psychiatric disorders as a function of exposure to increasing levels of stressful life events than do individuals who have one or two copies of the long (l) allele. Despite the reliability of this association, the mechanism by which this polymorphism confers risk for psychopathology in the presence of stress is not understood. This study was designed to examine the formulation that individuals who are homozygous for the s allele are characterized by a greater biological reactivity to stress than are their counterparts who have one or two copies of the l allele.Girls at high (n = 25) and low (n = 42) risk for depression by virtue of the presence or absence of a family history of this disorder were genotyped and exposed to a standardized laboratory stress task. Cortisol levels were assessed before the stressor, after the stressor, and during an extended recovery period.Girls who were homozygous for the s allele produced higher and more prolonged levels of cortisol in response to the stressor than did girls with an l allele.These findings indicate that the 5-HTTLPR polymorphism is associated with biological stress reactivity, which may increase susceptibility to depression in the face of stressful life events.

  View details for DOI 10.1016/j.biopsych.2007.10.008

  View details for Web of Science ID 000254945400005

  View details for PubMedID 18005940

  View details for PubMedCentralID PMC2373542

• Neural responses to monetary incentives in major depression BIOLOGICAL PSYCHIATRY Knutson, B., Bhanji, J. P., Cooney, R. E., Atlas, L. Y., Gotlib, I. H. 2008; 63 (7): 686-692

  Abstract

  Reduced responsiveness to positive incentives is a central feature of Major Depressive Disorder (MDD). In the present study, we compared neural correlates of monetary incentive processing in unmedicated depressed participants and never-depressed control subjects.Fourteen currently depressed and 12 never-depressed participants underwent functional magnetic resonance imaging while participating in a monetary incentive delay task. During the task, participants were cued to anticipate and respond to a rapidly presented target to gain or avoid losing varying amounts of money.Depressed and never-depressed participants did not differ in nucleus accumbens (NAcc) activation or in affective or behavioral responses during gain anticipation. Depressed participants did, however, exhibit increasing anterior cingulate activation during anticipation of increasing gains, whereas never-depressed participants showed increasing anterior cingulate activation during anticipation of increasing loss. Depressed participants also showed reduced discrimination of gain versus nongain outcomes.The present findings indicate that although unmedicated depressed individuals have the capacity to experience positive arousal and recruit NAcc activation during gain anticipation, they also exhibit increased anterior cingulate cortex activation, suggestive of increased conflict during anticipation of gains, in addition to showing reduced discrimination of gain versus nongain outcomes.

  View details for DOI 10.1016/j.biopsych.2007.07.023

  View details for Web of Science ID 000254107100008

  View details for PubMedID 17916330

  View details for PubMedCentralID PMC2290738

• Down-modulation of subgenual anterior cingulate cortex activity with real-time neurofeedback 63rd Annual Convention of the Society-of-Biological-Psychiatry Hamilton, J. P., Glover, G. H., Hsu, J., Gotlib, I. H. ELSEVIER SCIENCE INC. 2008: 73S–73S

  View details for Web of Science ID 000254163700235

• Neuroimaging and depression: Current status and unresolved issues CURRENT DIRECTIONS IN PSYCHOLOGICAL SCIENCE Gotlib, I. H., Hamilton, J. P. 2008; 17 (2): 159-163

  View details for Web of Science ID 000254807700019

• Updating the contents of working memory in depression: Interference from irrelevant negative material JOURNAL OF ABNORMAL PSYCHOLOGY Joormann, J., Gotfib, I. H. 2008; 117 (1): 182–92

  Abstract

  This study was designed to assess the effects of irrelevant emotional material on the ability to update the contents of working memory in depression. For each trial, participants were required to memorize 2 lists of emotional words and subsequently to ignore 1 of the lists. The impact of irrelevant emotional material on the ability to update the contents of working memory was indexed by response latencies on a recognition task in which the participants decided whether or not a probe was a member of the relevant list. The authors compared response latencies to probes from the irrelevant list to response latencies to novel probes of the same valence (intrusion effect). The results indicate that, compared to control participants in both neutral and sad mood states, depressed participants showed greater intrusion effects when presented with negative words. In an important finding, intrusion effects for negative words were correlated with self-reported rumination. These findings indicate that depression is associated with difficulties removing irrelevant negative material from working memory. Results also indicate that the increased interference from irrelevant negative material is associated with rumination.

  View details for DOI 10.1037/0021-843X.117.1.182

  View details for Web of Science ID 000252990000015

  View details for PubMedID 18266496

• Cardiovascular recovery from anticipated negative experiences that never occur Waugh, C. E., Panage, S., Mendes, W., Gotlib, I. H. BLACKWELL PUBLISHING. 2008: S83

  View details for Web of Science ID 000259144200347

• Remembering the good times: neural correlates of affect regulation NEUROREPORT Cooney, R. E., Joormann, J., Atlas, L. Y., Eugene, F., Gotlib, I. H. 2007; 18 (17): 1771-1774

  Abstract

  The ability to regulate one's mood state effectively is critical to emotional and physical health. Recent investigations have sought to delineate the neural mechanisms by which individuals regulate mood states and emotions, positing a critical role of a dorsal system that includes the dorsolateral prefrontal cortex and anterior cingulate. This study extended these efforts by examining the neural correlates of retrieving positive autobiographical memories while experiencing a negative mood state in a sample of healthy female adults. We demonstrated that mood-incongruent recall is associated with activation in ventrolateral and ventromedial prefrontal cortices (including orbitofrontal cortex and subgenual cingulate). These findings suggest that mood-incongruent recall differs from other affect regulation strategies by influencing mood through a ventral regulatory network.

  View details for Web of Science ID 000250901700004

  View details for PubMedID 18090309

• Depression and emotional reactivity: Variation among Asian Americans of east Asian descent and European Americans JOURNAL OF ABNORMAL PSYCHOLOGY Chentsova-Dutton, Y. E., Chu, J. P., Tsai, J. L., Rottenberg, J., Gross, J. J., Gotlib, I. H. 2007; 116 (4): 776-785

  Abstract

  Studies of Western samples (e.g., European Americans [EAs]) suggest that depressed individuals tend to show diminished emotional reactivity (J. G. Gehricke & A. J. Fridlund, 2002; G. E. Schwartz, P. L. Fair, P. Salt, M. R. Mandel, & G. L. Klerman, 1976a, 1976b). Do these findings generalize to individuals oriented to other cultures (e.g., East Asian cultures)? The authors compared the emotional reactions (i.e., reports of emotional experience, facial behavior, and physiological reactivity) of depressed and nondepressed EAs and Asian Americans of East Asian descent (AAs) to sad and amusing films. Their results were consistent with previous findings: Depressed EAs showed a pattern of diminished reactivity to the sad film (less crying, less intense reports of sadness) compared with nondepressed participants. In contrast, depressed AAs showed a pattern of heightened emotional reactivity (greater crying) compared with nondepressed participants. Across cultural groups, depressed and nondepressed participants did not differ in their reports of amusement or facial behavior during the amusing film. Physiological reactivity to the film clips did not differ between depressed and control participants for either cultural group. Thus, although depression may influence particular aspects of emotional reactivity across cultures (e.g., crying), the specific direction of this influence may depend on prevailing cultural norms regarding emotional expression.

  View details for DOI 10.1037/0021-843X.116.4.776

  View details for Web of Science ID 000250937700010

  View details for PubMedID 18020723

• Defining emotion: a clinical perspective SOCIAL SCIENCE INFORMATION SUR LES SCIENCES SOCIALES Gotlib, I. H. 2007; 46 (3): 387–91

  View details for DOI 10.1177/05390184070460030103

  View details for Web of Science ID 000250783700003

• Mood regulation in depression: Differential effects of distraction and recall of happy memories on sad mood JOURNAL OF ABNORMAL PSYCHOLOGY Joormann, J., Siemer, M., Gotlib, I. H. 2007; 116 (3): 484-490

  Abstract

  Recent research suggests that the recall of positive memories plays an important role in mood regulation. In this study, the authors examined the ability of currently depressed, formerly depressed, and never-depressed participants to regulate sad mood through the recall of positive memories or through distraction. Although improvement in mood was found for all participants in response to distraction, under instructions to recall positive memories, never-depressed participants' moods improved, whereas formerly depressed participants' sad moods remained unchanged. It is important to note that depressed participants exhibited a worsening of their sad moods after recalling positive memories. These results suggest both that depression is associated with an impaired ability to use positive recall to regulate a sad mood and that this impairment continues to be evident following recovery.

  View details for DOI 10.1037/0021-843X.116.3.484

  View details for Web of Science ID 000248642800005

  View details for PubMedID 17696704

• Severe life events predict specific patterns of change in cognitive biases in major depression PSYCHOLOGICAL MEDICINE Monroe, S. M., Slavich, G. M., Torres, L. D., Gotlib, I. H. 2007; 37 (6): 863-871

  Abstract

  A long-standing debate concerns whether dysfunctional cognitive processes and content play a causal role in the etiology of depression or more simply represent correlates of the disorder. There has been insufficient appreciation in this debate of specific predictions afforded by cognitive theory in relation to major life stress and changes in cognition over time. In this paper we present a novel perspective for investigating the etiological relevance of cognitive factors in depression. We hypothesize that individuals who experienced a severe life event prior to the onset of major depression will exhibit greater changes in dysfunctional attitudes over the course of the episode than will individuals without a severe life event.Fifty-three participants diagnosed with major depression were assessed longitudinally, approximately 1 year apart, with state-of-the-art measures of life stress and dysfunctional attitudes.Depressed individuals with a severe life event prior to episode onset exhibited greater changes in cognitive biases over time than did depressed individuals without a prior severe event. These results were especially pronounced for individuals who no longer met diagnostic criteria for major depression at the second assessment.Specific patterns of change in cognitive biases over the course of depression as a function of major life stress support the etiological relevance of cognition in major depression.

  View details for DOI 10.1017/S0033291707000281

  View details for Web of Science ID 000247050000009

  View details for PubMedID 17407615

  View details for PubMedCentralID PMC3631305

• Healthy individuals can use real-time fMRI neurofeedback to modulate activity in the subgenual anterior cingulate cortex 62nd Annual Meeting of the Society-of-Biological-Psychiatry Hamilton, J. P., Glover, G. H., Gotlib, I. H. ELSEVIER SCIENCE INC. 2007: 30S–30S

  View details for Web of Science ID 000245698100092

• Neural substrates of the negative memory bias in major depression Hamilton, J., Gotlib, I. H. ELSEVIER SCIENCE INC. 2007: 151S

  View details for Web of Science ID 000245698100486

• Biased processing of emotional information in girls at risk for depression JOURNAL OF ABNORMAL PSYCHOLOGY Joormann, J., Talbot, L., Gotlib, I. H. 2007; 116 (1): 135-143

  Abstract

  Researchers have documented that children of depressed mothers are at elevated risk for developing a depressive disorder themselves. There is currently little understanding, however, of what factors place these children at elevated risk. In the present study, the authors investigated whether never-disordered daughters whose mothers have experienced recurrent episodes of depression during their daughters' lifetime are characterized by biased processing of emotional information. Following a negative mood induction, participants completed an emotional-faces dot-probe task. Daughters at elevated risk for depression, but not control daughters of never-disordered mothers, selectively attended to negative facial expressions. In contrast, only control daughters selectively attended to positive facial expressions. These results provide support for cognitive vulnerability models of depression.

  View details for DOI 10.1037/0021-843X.116.1.135

  View details for Web of Science ID 000244162200013

  View details for PubMedID 17324024

• Major life events and major chronic difficulties are differentially associated with history of major depressive episodes JOURNAL OF ABNORMAL PSYCHOLOGY Monroe, S. M., Slavich, G. M., Torres, L. D., Gotlib, I. H. 2007; 116 (1): 116-124

  Abstract

  Major life events have been found to precede onsets of a 1st lifetime episode of depression more commonly than subsequent recurrences. Despite general empirical support for this finding, few data directly address how the role of major life events may change over successive recurrences. Further, little research has examined major chronic difficulties in relation to a 1st lifetime episode versus a recurrence of depression. The present study tested the associations between major life events and major difficulties in relation to lifetime history of depressive episodes in a sample of 96 individuals diagnosed with major depression. Using investigator-based measures of life stress, the authors found that, whereas major life events were associated with fewer lifetime episodes, major chronic difficulties were related to more prior episodes. These findings are discussed in terms of underlying mechanisms that may account for the changing role of major life stress over successive recurrences of depression.

  View details for DOI 10.1037/0021-843X.116.1.116

  View details for Web of Science ID 000244162200011

  View details for PubMedID 17324022

  View details for PubMedCentralID PMC3631311

• Does processing of emotional stimuli predict symptomatic improvement and diagnostic recovery from major depression? EMOTION Johnson, S. L., Joormann, J., Gotlib, I. H. 2007; 7 (1): 201-206

  Abstract

  This study was designed to examine whether processing of emotional stimuli predicts both symptomatic improvement and recovery from depression. Participants diagnosed with Major Depressive Disorder (MDD) (N=63) completed information-processing tasks to assess attention to and memory for sad, physically threatening, socially threatening, and happy stimuli. At a follow-up session an average of nine months later, participants were reassessed to determine diagnostic status and depression severity. None of the measure of attention or memory predicted diagnostic status at follow-up. Those depressed participants who remembered a higher proportion of positive words that they had endorsed as self-descriptive exhibited greater symptomatic improvement. After controlling for memory of positive self-referential words, attentional measures did not predict symptomatic change. These results are consistent with a growing literature highlighting the importance of emotionally relevant memory processes for understanding the course of major depression.

  View details for DOI 10.1037/1528-3542.7.1.201

  View details for Web of Science ID 000244491500018

  View details for PubMedID 17352575

  View details for PubMedCentralID PMC2847494

• Selective attention to emotional faces following recovery from depression JOURNAL OF ABNORMAL PSYCHOLOGY Joormann, J., Gotlib, I. H. 2007; 116 (1): 80-85

  Abstract

  This study was designed to examine attentional biases in the processing of emotional faces in currently and formerly depressed participants and healthy controls. Using a dot-probe task, the authors presented faces expressing happy or sad emotions paired with emotionally neutral faces. Whereas both currently and formerly depressed participants selectively attended to the sad faces, the control participants selectively avoided the sad faces and oriented toward the happy faces, a positive bias that was not observed for either of the depressed groups. These results indicate that attentional biases in the processing of emotional faces are evident even after individuals have recovered from a depressive episode. Implications of these findings for understanding the roles of cognitive and interpersonal functioning in depression are discussed.

  View details for DOI 10.1037/0021-843X.116.1.80

  View details for Web of Science ID 000244162200007

  View details for PubMedID 17324018

• Amygdala reactivity and mood-congruent memory in individuals at risk for depressive relapse BIOLOGICAL PSYCHIATRY Ramel, W., Goldin, P. R., Eyler, L. T., Brown, G. G., Gotlib, I. H., McQuaid, J. R. 2007; 61 (2): 231-239

  Abstract

  According to cognitive diathesis-stress theories, a latent cognitive vulnerability to depression is activated by negative affect in individuals at risk for depressive relapse. This vulnerability can manifest as mood-congruent memory during sad mood and may involve amygdala response, which is implicated in memory for emotionally arousing stimuli. This study examined whether amygdala modulates memory for negatively valenced words before and after a sad mood induction in healthy individuals with and without a history of recurrent major depression.Fourteen unmedicated remitted depressed (RD) and 14 matched never depressed (ND) individuals were scanned using functional magnetic resonance imaging (fMRI) while performing a self-referent encoding/evaluation task (SRET) preceding and following a sad mood challenge. After each SRET, participants' free recall was assessed.Following sad mood induction, bilateral amygdala response during encoding of valenced words predicted increased recall of negative self-referent words for a subset of RD participants. This association was not present before the sad mood induction and was not evident in individuals without a history of depression, regardless of mood state.These results are consistent with cognitive diathesis-stress theories and suggest a role for the amygdala in modulating mood-congruent memory during transient sad mood in individuals who are vulnerable to depression relapse.

  View details for DOI 10.1016/j.biopsych.2006.05.004

  View details for Web of Science ID 000243454900015

  View details for PubMedID 16950223

• Amygdala activation in the processing of neutral faces in social anxiety disorder: Is neutral really neutral? PSYCHIATRY RESEARCH-NEUROIMAGING Cooney, R. E., Atlas, L. Y., Joormann, J., Eugene, F., Gotlib, I. H. 2006; 148 (1): 55-59

  Abstract

  Previous research has suggested that Social Anxiety Disorder (SAD) is associated with a tendency to interpret ambiguous social stimuli in a threatening manner. The present study used event-related functional magnetic resonance imaging to examine patterns of neural activation in response to the processing of neutral facial expressions in individuals diagnosed with SAD and healthy controls (CTLs). The SAD participants exhibited a different pattern of amygdala activation in response to neutral faces than did the CTL participants, suggesting a neural basis for the biased processing of ambiguous social information in SAD individuals.

  View details for DOI 10.1016/j.pscychresns.2006.05.003

  View details for Web of Science ID 000242668900006

  View details for PubMedID 17030117

• Is this happiness I see? Biases in the identification of emotional facial expressions in depression and social phobia JOURNAL OF ABNORMAL PSYCHOLOGY Joormann, J., Gotlib, I. H. 2006; 115 (4): 705-714

  Abstract

  The present study was designed to examine the operation of depression-specific biases in the identification or labeling of facial expression of emotions. Participants diagnosed with major depression and social phobia and control participants were presented with faces that expressed increasing degrees of emotional intensity, slowly changing from a neutral to a full-intensity happy, sad, or angry expression. The authors assessed individual differences in the intensity of facial expression of emotion that was required for the participants to accurately identify the emotion being expressed. The depressed participants required significantly greater intensity of emotion than did the social phobic and the control participants to correctly identify happy expressions and less intensity to identify sad than angry expressions. In contrast, social phobic participants needed less intensity to correctly identify the angry expressions than did the depressed and control participants and less intensity to identify angry than sad expressions. Implications of these results for interpersonal functioning in depression and social phobia are discussed.

  View details for DOI 10.1037/0021-843X.115.4.705

  View details for Web of Science ID 000242132400006

  View details for PubMedID 17100528

• Adaptive and maladaptive components of rumination? Diagnostic specificity and relation to depressive biases Conference on Clinical Cognition Joormann, J., Dkane, M., Gotlib, I. H. ASSOC ADV BEHAVIOR THERAPY. 2006: 269–80

  Abstract

  The present study investigated the validity of the two-factor solution of items selected from the Rumination Scale of the Response Style Questionnaire proposed by Treynor, Gonzalez, and Nolen-Hoeksema (2003). In the first part of this study we used samples of currently depressed (MDD), formerly depressed (FD), socially anxious (SP), and healthy control participants to examine whether the brooding and reflective pondering components differentiate participants with an anxiety disorder from participants with depression. In the second part of this study we examined whether these components of rumination were differentially related to cognitive biases in depression. Overall, the MDD group exhibited higher brooding scores than did all other groups; SP and FD groups did not differ from each other but obtained higher brooding scores than did the control participants. Only the MDD and the control groups differed on the reflective pondering factor. Importantly, brooding and reflective pondering were differentially related to cognitive biases. Specifically, the correlation between brooding/reflective pondering and memory bias was not significant when depressive symptoms were partialed out. The correlation between brooding and attentional bias for sad faces, however, remained significant even when current depressive symptoms were taken into account. In sum, our results support the formulation that rumination is composed of an adaptive reflective pondering factor and a maladaptive brooding factor.

  View details for Web of Science ID 000248377900007

  View details for PubMedID 16942978

• A little emotion goes a long way: Increased amygdala responses to momentary emotional stimuli but blunted responses to repeated stimuli in unipolar depression Siegle, G. J., Gotlib, I. H., Whalen, P. J., Thase, M. E. ELSEVIER SCIENCE INC. 2006: 9S

  View details for Web of Science ID 000236767300028

• Idiographic autobiographical memories in major depressive disorder COGNITION & EMOTION Rottenberg, J., HILDNER, J. C., Gotlib, I. H. 2006; 20 (1): 114-128

  View details for DOI 10.1080/02699930500286299

  View details for Web of Science ID 000235287300007

• Subgenual anterior cingulate activation to valenced emotional stimuli in major depression NEUROREPORT Gotlib, I. H., Sivers, H., Gabrieli, J. D., Whitfield-Gabrieli, S., Goldin, P., Minor, K. L., Canli, T. 2005; 16 (16): 1731-1734

  Abstract

  Major depression has been associated with anomalous activation in the subgenual anterior cingulate cortex, but its response to emotional stimuli is poorly understood. The primary goal of this study was to compare levels of activation in the subgenual anterior cingulate cortex of diagnosed depressed and nondepressed participants in response to happy and sad facial expressions of affect. Whereas cognitive theories of depression predict increased activation to negative stimuli, depressed participants were found to exhibit increased activation to both types of stimuli in the subgenual anterior cingulate cortex. Importantly, the loci were in different regions of the subgenual anterior cingulate cortex, suggesting that there is functional specialization in the processing of negatively and positively valenced stimuli.

  View details for Web of Science ID 000233277700002

  View details for PubMedID 16237317

• Remembering the good, forgetting the bad: Intentional forgetting of emotional material in depression JOURNAL OF ABNORMAL PSYCHOLOGY Joormann, J., Hertel, P. T., Brozovich, F., Gotlib, I. H. 2005; 114 (4): 640-648

  Abstract

  The authors examined intentional forgetting of negative material in depression. Participants were instructed to not think about emotional nouns that they had learned to associate with a neutral cue word. The authors provided participants with multiple occasions to suppress the unwanted words. Overall, depressed participants successfully forgot negative words. Moreover, the authors obtained a clear practice effect. However, forgetting came at a cost: Compared with the nondepressed participants and with the depressed participants who were instructed to forget positive words, depressed participants who were instructed to forget negative words showed significantly worse recall of the baseline words. These results indicate that training depressed individuals in intentional forgetting could prove to be an effective strategy to counteract automatic ruminative tendencies and mood-congruent biases.

  View details for DOI 10.1037/0021-843X.114.4.640

  View details for Web of Science ID 000233760700015

  View details for PubMedID 16351371

• Emotion context insensitivity in major depressive disorder JOURNAL OF ABNORMAL PSYCHOLOGY Rottenberg, J., Gross, J. J., Gotlib, I. H. 2005; 114 (4): 627-639

  Abstract

  The present study tested 3 competing views of how depression alters emotional reactivity: positive attenuation (reduced positive), negative potentiation (increased negative), and emotion context insensitivity (ECI; reduced positive and negative). Normative and idiographic stimuli that elicited happy, sad, and neutral states were presented to currently depressed, formerly depressed, and healthy control individuals while experiential, behavioral, and autonomic responses were measured. Currently depressed individuals reported less sadness reactivity and less happiness experience across all conditions than did the other participants, and they exhibited a more dysphoric response to idiographic than to normative stimuli. Overall, data provide partial support for the positive attenuation and ECI views. Depression may produce mood-state-dependent changes in emotional reactivity that are most pronounced in emotion experience reports.

  View details for DOI 10.1037/0021-843X.114.4.627

  View details for Web of Science ID 000233760700014

  View details for PubMedID 16351385

• Amygdala reactivity to emotional faces predicts improvement in major depression NEUROREPORT Canli, T., Cooney, R. E., Goldin, P., Shah, M., Sivers, H., Thomason, M. E., Whitfield-Gabrieli, S., Gabrieli, J. D., Gotlib, I. H. 2005; 16 (12): 1267-1270

  Abstract

  Behavioral studies suggest that emotional reactivity in depressed persons predicts subsequent symptom reduction. Using functional magnetic resonance imaging in a prospective study, we show that greater amygdala activation to emotional facial expressions among depressed patients predicts symptom reduction 8 months later, controlling for initial depression severity and medication status. Functional magnetic resonance imaging may thus be used as a method to identify neural markers in depressed patients at risk for poor outcome.

  View details for Web of Science ID 000231492600003

  View details for PubMedID 16056122

• Selective attention in dysphoric individuals: The role of affective interference and inhibition COGNITIVE THERAPY AND RESEARCH Gotlib, I. H., Yue, D. N., Joormann, J. 2005; 29 (4): 417-432

  View details for DOI 10.1007/s10608-005-5753-6

  View details for Web of Science ID 000231600100004

• Stability of DSM-IV criterion symptoms for major depressive disorder JOURNAL OF PSYCHIATRIC RESEARCH Minor, K. L., Champion, J. E., Gotlib, I. H. 2005; 39 (4): 415-420

  Abstract

  Given the chronic and recurrent nature of major depressive disorder (MDD), it is important to understand whether specific symptoms are stable over time or vary over the course of the disorder. This is the first longitudinal investigation examining the stability of the nine criterion symptoms of depression, as specified in the DSM-IV, among diagnosed depressed adults who were not recovered at follow-up. In this study, participants were assessed twice, ten months apart, with the structured clinical interview for DSM-IV, and stability of the nine criterion symptoms of MDD was examined. Findings indicate strong stability in individuals' symptom profiles. Among individuals who were clinically depressed at both assessments, there were no statistically significant fluctuations in specific symptoms endorsed. Changes in symptom endorsement among individuals who no longer met diagnostic criteria for MDD at Time 2 were attributable to reduced severity (i.e., number of symptoms) rather than to inconsistency of symptom endorsement. These results indicate that depressed individuals experience essentially the same pattern of specific symptoms over the course of a year. Variation in clinical course is likely to be attributable more to fluctuations in overall severity than to changes in specific symptoms of depression.

  View details for DOI 10.1016/j.jpsychires.2004.11.001

  View details for Web of Science ID 000230295900010

  View details for PubMedID 15804392

• Emotional intensity of idiographic sad memories in depression predicts symptom levels 1 year later EMOTION Rottenberg, J., Joormann, J., Brozovich, F., Gotlib, I. H. 2005; 5 (2): 238–42

  Abstract

  When cued with generic happy and sad words, depressed individuals have been found to articulate contextually impoverished memories of autobiographical events. Although this pattern predicts a worse symptomatic course of disorder in some depressed samples, longitudinal findings with the cue-word paradigm are inconsistent. To address the etiological significance of autobiographical memories outside the cue-word paradigm, the authors used an idiographic interview in which depressed participants generated memories of their happiest and saddest lifetime events. Each memory was coded for detail and emotional intensity. At a 1-year follow-up, participants' levels of depressive symptoms were reassessed. Lower emotional intensity of saddest memories predicted higher levels of depressive symptoms at follow-up. Several implications for understanding sadness and emotional disclosure in depression are discussed.

  View details for DOI 10.1037/1528-3542.5.2.238

  View details for Web of Science ID 000230443800012

  View details for PubMedID 15982090

• Vagal withdrawal to a sad film predicts subsequent recovery from depression PSYCHOPHYSIOLOGY Rottenberg, J., Salomon, K., Gross, J. J., Gotlib, I. H. 2005; 42 (3): 277-281

  Abstract

  Cardiac vagal tone, as indexed by abnormalities in the level and/or reactivity of respiratory sinus arrhythmia (RSA), has been related to psychiatric impairment, including risk for depression. Longitudinal studies of depression have focused on RSA levels and have found mixed support for the hypothesis that low RSA levels predict a more pernicious course of depression. The current investigation focuses on the relation between RSA reactivity and the course of depression. We measured depressed persons' RSA reactivity to sadness-, fear-, and amusement-inducing emotion films and reassessed participants' diagnostic status 6 months later. Depressed persons who exhibited a higher degree of vagal withdrawal to the sad film were more likely to recover from depression. Implications for the study of RSA in depression are discussed.

  View details for DOI 10.1111/j.1469-8986.2005.00289.x

  View details for Web of Science ID 000229666500004

  View details for PubMedID 15943681

• Attention and memory biases in the offspring of parents with bipolar disorder: indications from a pilot study JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY Gotlib, I. H., Traill, S. K., Montoya, R. L., Joormann, J., Chang, K. 2005; 46 (1): 84-93

  Abstract

  Although children of bipolar parents are at heightened risk for developing emotional disorders, the processes underlying this vulnerability are not well understood. This study examined biases in the processing of emotional stimuli as a potential vulnerability marker of bipolar disorder.Sixteen children of bipolar parents who did not show any indication of having an emotional disorder at the time of testing and ten children of never-disordered control parents underwent a negative mood induction designed to activate cognitive schemas and were then administered an emotion Stroop task and a self-referent encoding task.Children of bipolar parents were found to exhibit an attentional bias towards social-threat and manic-irritable words. Furthermore, although high- and low-risk children did not differ in their endorsement of positive and negative words as self-descriptive, the high-risk children demonstrated better recall of negative words than did the low-risk children.Thus, children without a mood disorder who are at high risk for developing a mood disorder were found to exhibit biases in attention and memory that are similar to those found for bipolar and unipolar depressed adults, suggesting that children at increased risk for affective disorder are characterized by potentially pathogenic cognitive structures that can be activated by sad mood. These findings offer insights into mechanisms of cognitive vulnerability for bipolar disorders.

  View details for PubMedID 15660646

• An fMRI investigation of emotion and emotion regulation in depression 12th Annual Meeting of the Cognitive-Neuroscience-Society Robertson, E., Ochsner, K., Ray, R., Cooper, J., Gabrieli, J., Gotlib, I., GROSS, J. MIT PRESS. 2005: 198–198

  View details for Web of Science ID 000227878701237

• Brain activation to emotional words in depressed vs healthy subjects NEUROREPORT Canli, T., Sivers, H., Thomason, M. E., Whitfield-Gabrieli, S., Gabrieli, J. D., Gotlib, I. H. 2004; 15 (17): 2585-2588

  Abstract

  Depression involves either enhanced processing of negative stimuli or diminished processing of positive stimuli. We used functional magnetic resonance imaging to assess brain activation in depressed vs healthy participants. Fifteen participants diagnosed with major depressive disorder and 15 controls were scanned during a lexical decision task involving neutral, happy, sad, and threat-related words. For happy words, depressed subjects exhibited less activation than did controls to happy words in fronto-temporal and limbic regions. For sad words, depressed subjects showed more activation than did controls in the inferior parietal lobule and less activation in the superior temporal gyrus and cerebellum, suggesting a complex activation pattern that varies for neural sub-circuits that may be associated with different cognitive or behavioral processes.

  View details for Web of Science ID 000226068600005

  View details for PubMedID 15570157

• Coherence and specificity of information-processing biases in depression and social phobia JOURNAL OF ABNORMAL PSYCHOLOGY Gotlib, I. H., Kasch, K. L., TRAILL, S., Joormann, J., Arnow, B. A., Johnson, S. L. 2004; 113 (3): 386-398

  Abstract

  Research has not resolved whether depression is associated with a distinct information-processing bias, whether the content of the information-processing bias in depression is specific to themes of loss and sadness, or whether biases are consistent across the tasks most commonly used to assess attention and memory processing. In the present study, participants diagnosed with major depression, social phobia, or no Axis I disorder, completed several information-processing tasks assessing attention and memory for sad, socially threatening, physically threatening, and positive stimuli. As predicted, depressed participants exhibited specific biases for stimuli connoting sadness; social phobic participants did not evidence such specificity for threat stimuli. It is important to note that the different measures of bias in memory and attention were not systematically intercorrelated. Implications for the study of cognitive bias in depression, and for cognitive theory more broadly, are discussed.

  View details for DOI 10.1037/0021-843x.113.3.386

  View details for Web of Science ID 000223137900003

  View details for PubMedID 15311984

• Gender differences in depression: the role of personality factors PSYCHIATRY RESEARCH Goodwin, R. D., Gotlib, I. H. 2004; 126 (2): 135-142

  Abstract

  The goal of the study was to determine the association between gender and the Big Five personality factors, and to identify the role of personality factors in the association between gender and depression among adults in the United States. Data were drawn from the Midlife Development in the United States Survey (N=3032). Multivariate analysis of variance (MANOVA) was used to examine gender differences on the Big Five personality factors (i.e. agreeableness, neuroticism, openness to experience, extraversion, and conscientiousness). Multivariate logistic regression analyses were conducted to examine the relation between gender and depression, and to test whether this association is moderated by neuroticism. Levels of neuroticism, agreeableness, extraversion, and conscientiousness were significantly higher among females than among males; in contrast, level of openness to experience was significantly higher among males. Female gender was associated with increased odds of experiencing depression. Results showed that neuroticism played a significant contributory role in the relationship between being female and major depression, though the role of gender remained statistically significant after adjustment. These data suggest that gender differences in personality factors, specifically neuroticism, may play a key role in the well-documented gender difference in depression. Our findings indicate that neuroticism may moderate the association between female gender and increased risk of depression among adults. These findings require replication using longitudinal data.

  View details for DOI 10.1016/j.psychres.2003.12.024

  View details for Web of Science ID 000221629000005

  View details for PubMedID 15123392

• Attentional biases for negative interpersonal stimuli in clinical depression. Journal of abnormal psychology Gotlib, I. H., Krasnoperova, E., Yue, D. N., Joormann, J. 2004; 113 (1): 121-135

  Abstract

  An information-processing paradigm was used to examine attentional biases in clinically depressed participants, participants with generalized anxiety disorder (GAD), and nonpsychiatric control participants for faces expressing sadness, anger, and happiness. Faces were presented for 1000 ms, at which point depressed participants had directed their attention selectively to depression-relevant (i.e., sad) faces. This attentional bias was specific to the emotion of sadness; the depressed participants did not exhibit attentional biases to the angry or happy faces. This bias was also specific to depression; at 1000 ms, participants with GAD were not attending selectively to sad, happy, or anxiety-relevant (i.e., angry) faces. Implications of these findings for both the cognitive and the interpersonal functioning of depressed individuals are discussed and directions for future research are advanced.

  View details for PubMedID 14992665

• Attentional biases for negative interpersonal stimuli in clinical depression JOURNAL OF ABNORMAL PSYCHOLOGY Gotlib, I. H., Krasnoperova, E., Yue, D. N., Joormann, J. 2004; 113 (1): 127-135

  Abstract

  An information-processing paradigm was used to examine attentional biases in clinically depressed participants, participants with generalized anxiety disorder (GAD), and nonpsychiatric control participants for faces expressing sadness, anger, and happiness. Faces were presented for 1000 ms, at which point depressed participants had directed their attention selectively to depression-relevant (i.e., sad) faces. This attentional bias was specific to the emotion of sadness; the depressed participants did not exhibit attentional biases to the angry or happy faces. This bias was also specific to depression; at 1000 ms, participants with GAD were not attending selectively to sad, happy, or anxiety-relevant (i.e., angry) faces. Implications of these findings for both the cognitive and the interpersonal functioning of depressed individuals are discussed and directions for future research are advanced.

  View details for DOI 10.1037/0021-843X.113.1.127

  View details for Web of Science ID 000189119700014

• Psychosocial functioning of young adults who have experienced and recovered from major depressive disorder during adolescence JOURNAL OF ABNORMAL PSYCHOLOGY Lewinsohn, P. M., Rohde, P., Seeley, J. R., Klein, D. N., Gotlib, I. H. 2003; 112 (3): 353-363

  Abstract

  The authors examined whether adolescent major depressive disorder (MDD) was associated with difficulties in young adult functioning and whether differences would remain significant after accounting for nonmood disorder, MDD recurrence, functioning in adolescence, or current mood state. A total of 941 participants were assessed twice during adolescence and at age 24. In unadjusted analyses, adolescent MDD was associated with most young adult functioning measures. Associations were not due to interactions with adolescent comorbidity, but differences in global functioning and mental health treatment appeared as a result of MDD recurrence. Accounting for levels of functioning in adolescence or for current depression at age 24 eliminated the remaining associations. The implications of these findings for efforts to prevent MDD in adolescence are discussed.

  View details for DOI 10.1037/0021-843X.112.3.353

  View details for PubMedID 12943014

• Amygdalar activation associated with happy facial expressions in adolescents: A 3-T functional MRI study JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY Yang, T. T., Menon, V., Reid, A. J., Gotlib, I. H., Reiss, A. L. 2003; 42 (8): 979-985

  Abstract

  To study the possible role of the amygdala in the recognition of happy and sad facial expressions in adolescents aged 13 to 17 years.Twelve healthy adolescents (6 females and 6 males) underwent noninvasive 3-Tesla functional magnetic resonance imaging while viewing pictures of happy, sad, and neutral facial expressions.Happy faces produced significant bilateral amygdalar activation when compared with neutral faces (p <.05, corrected). Sad faces relative to neutral did not produce significant amygdalar activation.These results extend the role of the amygdala in adolescents to include the recognition of happy facial expressions. They demonstrate the feasibility of using happy facial expressions to noninvasively study amygdalar function in adolescents and establish a baseline against which the amygdalar response to emotional stimuli in several psychiatric conditions may be compared.

  View details for DOI 10.1097/01.CHI.0000046886.27264.BA

  View details for Web of Science ID 000184302700016

  View details for PubMedID 12874501

• Individualized measurement of irrational beliefs in remitted depressives JOURNAL OF CLINICAL PSYCHOLOGY Solomon, A., Arnow, B. A., Gotlib, I. H., Wind, B. 2003; 59 (4): 439-455

  Abstract

  Recent reviews of cognitive theories of depression have noted that individualized assessment strategies might help to resolve mixed findings regarding the stability of depressotypic beliefs and attitudes. We describe encouraging results for an individualized measure of one such cognitive construct, irrational beliefs. Twenty depression-prone women (recurrent major depressives in full remission) and twenty closely matched never-depressed controls completed leading forced-choice measures of irrational beliefs (the Belief Scale; BS) and sociotropy-autonomy (The Revised Personal Style Inventory), as well as the Specific Demands on Self Scale (SDS). The BS requires participants to rate their agreement with twenty preselected statements of irrational beliefs, while the SDS focuses on whether participants harbor any strongly held irrational beliefs, even if uncommon or idiosyncratic. Consistent with previous research, there were no group differences on the traditional measure of irrational beliefs. In contrast, depression-prone participants strongly exceeded controls on the SDS, and this difference persisted after controlling for residual depression, anxiety symptoms, anxiety diagnoses, sociotropy, and autonomy. These findings provide some initial support for a key assumption of the rational-emotive model of depression, and, more broadly, suggest that individualized assessment strategies may help researchers capture the core negative beliefs of asymptomatic individuals, even in the absence of mood or cognitive priming.

  View details for DOI 10.1002/jclp.10081

  View details for Web of Science ID 000181750000004

  View details for PubMedID 12652636

• Vagal rebound during resolution of tearful crying among depressed and nondepressed individuals PSYCHOPHYSIOLOGY Rottenberg, J., Wilhelm, F. H., Gross, J. J., Gotlib, I. H. 2003; 40 (1): 1-6

  Abstract

  Respiratory sinus arrhythmia (RSA) is an index of the vagal control of heart rate that is associated with emotion regulatory capacity. To examine RSA in depressed and nondepressed participants in the context of an emotion-regulatory challenge, we presented a sad film to induce crying, a behavior associated with heightened parasympathetic activation. We predicted that nondepressed persons who cried would show elevations in RSA during the onset and the resolution of crying. By contrast, we predicted that depressed individuals who cried would fail to exhibit increased RSA over the course of their crying episodes. As hypothesized, nondepressed participants exhibited RSA increases that accompanied the resolution of tearful crying, consistent with a homeostatic function for crying, whereas depressed subjects who cried did not exhibit increased RSA. Results suggest that the physiological self-regulatory mechanisms invoked by crying are compromised in depression.

  View details for Web of Science ID 000180455300001

  View details for PubMedID 12751799

• Behavioral activation and inhibition systems and the severity and course of depression JOURNAL OF ABNORMAL PSYCHOLOGY Kasch, K. L., Rottenberg, J., Arnow, B. A., Gotlib, I. H. 2002; 111 (4): 589-597

  Abstract

  Theorists have proposed that depression is associated with abnormalities in the behavioral activation (BAS) and behavioral inhibition (BIS) systems. In particular, depressed individuals are hypothesized to exhibit deficient BAS and overactive BIS functioning. Self-reported levels of BAS and BIS were examined in 62 depressed participants and 27 nondepressed controls. Clinical functioning was assessed at intake and at 8-month follow-up. Relative to nondepressed controls, depressed participants reported lower BAS levels and higher BIS levels. Within the depressed group, lower BAS levels were associated with greater concurrent depression severity and predicted worse 8-month outcome. Levels of both BIS and BAS showed considerable stability over time and clinical state. Overall, results suggest that BAS dysregulation exacerbates the presentation and course of depressive illness.

  View details for DOI 10.1037//0021-843X.111.4.589

  View details for Web of Science ID 000178941600006

  View details for PubMedID 12428772

• Amygdalar activation associated with positive and negative facial expressions NEUROREPORT Yang, T. T., Menon, V., Eliez, S., Blasey, C., White, C. D., Reid, A. J., Gotlib, I. H., Reiss, A. L. 2002; 13 (14): 1737-1741

  Abstract

  Most theories of amygdalar function have underscored its role in fear. One broader theory suggests that neuronal activation of the amygdala in response to fear-related stimuli represents only a portion of its more widespread role in modulating an organism's vigilance level. To further explore this theory, the amygdalar response to happy, sad, angry, fearful, and neutral faces in 17 subjects was characterized using 3 T fMRI. Utilizing a random effects model and hypothesis-driven analytic strategy, it was observed that each of the four emotional faces was associated with reliable bilateral activation of the amygdala compared with neutral. These findings suggest a broader role for the amygdala in modulating the vigilance level during the perception of several negative and positive facial emotions.

  View details for Web of Science ID 000179156600009

  View details for PubMedID 12395114

• Stability of retrospective reports in depression: Traumatic events, past depressive episodes, and parental psychopathology JOURNAL OF HEALTH AND SOCIAL BEHAVIOR Schraedley, P. K., Turner, R. J., Gotlib, I. H. 2002; 43 (3): 307-316

  Abstract

  Research findings based on the retrospective reports of depressed individuals have long been held suspect because of possible negative reporting biases associated with depression. In the present study we assess the stability of retrospective reports of past traumatic events, past depressive episodes, parental depression, and parental substance abuse in a sample of 234 adults whose depression status changed over two assessments conducted one year apart. Depression status was found to affect reporting of number of past depressive episodes and past traumatic events, but not reporting of parental psychopathology. Implications of these findings are discussed for research that relies on the retrospective self-reports of depressed participants.

  View details for Web of Science ID 000179297000004

  View details for PubMedID 12467255

• Respiratory sinus arrhythmia as a predictor of outcome in major depressive disorder JOURNAL OF AFFECTIVE DISORDERS Rottenberg, J., Wilhelm, F. H., Gross, J. J., Gotlib, I. H. 2002; 71 (1-3): 265-272

  Abstract

  Respiratory sinus arrhythmia (RSA) is a noninvasive measure of parasympathetic tone that has been related to emotion regulatory capacity. While some previous work indicates that clinically depressed persons exhibit lower levels of RSA than do normal controls, there is nevertheless considerable between-subject variation in RSA among depressed persons. The current study evaluated the significance of variation in RSA among depressed persons by examining whether levels of RSA predicted concurrent symptomatology and the course of depressive illness.The RSA levels of 55 diagnosed depressed individuals were assessed during a paced breathing procedure at Time 1. Six months later (Time 2), participants were interviewed again to determine whether or not each had fully recovered from depression. Multinomial regression analyses were conducted to examine whether RSA predicted Time 2 clinical status.Although RSA levels were not related to overall depression severity, they were associated with specific symptoms of depression: RSA was positively associated with the report of sadness and negatively associated with the report of suicidality. More strikingly, however, higher levels of RSA at Time 1 predicted non-recovery from depression at Time 2, even when statistically controlling for initial depression severity, age and medication use.Treatment and medication use were not controlled during the follow-up period and a group of nonpsychiatric controls was not included in this study.A relatively high level of RSA among depressed individuals predicts a more pernicious course of illness than do lower RSA levels.

  View details for Web of Science ID 000177824700033

  View details for PubMedID 12167527

• Amygdala response to happy faces as a function of extraversion SCIENCE Canli, T., Sivers, H., Whitfield, S. L., Gotlib, I. H., Gabrieli, J. D. 2002; 296 (5576): 2191-2191

  View details for Web of Science ID 000176379000048

  View details for PubMedID 12077407

• Sadness and Amusement Reactivity Differentially Predict Concurrent and Prospective Functioning in Major Depressive Disorder EMOTION Rottenberg, J., Kasch, K. L., Gross, J. J., Gotlib, I. H. 2002; 2 (2): 135-146

  Abstract

  Depressed individuals often fail to react to emotionally significant stimuli. The significance of this pattern of emotional dysregulation in depression is poorly understood. In the present study, depressed and nondepressed participants viewed standardized neutral, sad, fear, and amusing films; and experiential, behavioral, and physiological responses to each film were assessed. Compared with nondepressed controls, depressed participants reported sadness and amusement in a flattened, context-insensitive manner. Those depressed participants who reported the least reactivity to the sad film exhibited the greatest concurrent impairment. Prospectively, the depressed participant who exhibited the least behavioral and heart rate reactivity to the amusing film were the least likely to recover from depression. Loss of the context-appropriate modulation of emotion in depression may reflect a core feature of emotion dysregulation in this disorder.

  View details for DOI 10.1037//1528-3542.2.2.135

  View details for Web of Science ID 000208224500004

  View details for PubMedID 12899187

• Crying threshold and intensity in major depressive disorder JOURNAL OF ABNORMAL PSYCHOLOGY Rottenberg, J., Gross, J. J., Wilhelm, F. H., Gotlib, I. H. 2002; 111 (2): 302-312

  Abstract

  Clinical lore suggests that depression is associated with frequent and intense crying. To test these postulations empirically, a standardized cry-evoking stimulus was presented to depressed and nondepressed participants, and their likelihood of crying and the magnitude of crying-related changes in their emotion experience, behavior, and autonomic physiology were compared. Unexpectedly, crying was no more likely in depressed than in nondepressed participants. Within the nondepressed group, participants who cried exhibited increases in the report and display of sadness and had greater cardiac and electrodermal activation than did participants who did not cry. There was less evidence of this crying-related emotional activation within the depressed group. The lack of emotional activation among clinically depressed participants who cried provides a tantalizing clue concerning how emotions are dysregulated in this disorder.

  View details for DOI 10.1037//0021-843X.111.2.302

  View details for Web of Science ID 000175078600009

  View details for PubMedID 12003451

• Natural course of adolescent major depressive disorder in a community sample: Predictors of recurrence in young adults AMERICAN JOURNAL OF PSYCHIATRY Lewinsohn, P. M., Rohde, P., Seeley, J. R., Klein, D. N., Gotlib, L. H. 2000; 157 (10): 1584-1591

  Abstract

  The primary purpose was to identify factors related to the recurrence of major depressive disorder during young adulthood (19-23 years of age) in a community sample of formerly depressed adolescents.A total of 274 participants with adolescent-onset major depressive disorder were assessed twice during adolescence and again after their 24th birthday. Lifetime psychiatric information was obtained from their first-degree relatives. Adolescent predictor variables included demographic characteristics, psychosocial variables, characteristics of adolescent major depressive disorder, comorbidity, family history of major depressive disorder and nonmood disorder, and antisocial and borderline personality disorder symptoms.Low levels of excessive emotional reliance, a single episode of major depressive disorder in adolescence, low proportion of family members with recurrent major depressive disorder, low levels of antisocial and borderline personality disorder symptoms, and a positive attributional style (males only) independently predicted which formerly depressed adolescents would remain free of future psychopathology. Female gender, multiple major depressive disorder episodes in adolescence, higher proportion of family members with recurrent major depressive disorder, elevated borderline personality disorder symptoms, and conflict with parents (females only) independently predicted recurrent major depressive disorder. Comorbid anxiety and substance use disorders in adolescence and elevated antisocial personality disorder symptoms independently distinguished adolescents who developed recurrent major depressive disorder comorbid with nonmood disorder from those who developed pure major depressive disorder.Formerly depressed adolescents with the risk factors identified in this study are at elevated risk for recurrence of major depressive disorder during young adulthood and therefore warrant continued monitoring and preventive or prophylactic treatment.

  View details for PubMedID 11007711

• Stroop interference following mood induction: Emotionality, mood congruence, and concern relevance COGNITIVE THERAPY AND RESEARCH Gilboa-Schechtman, E., Revelle, W., Gotlib, I. H. 2000; 24 (5): 491–502

  View details for DOI 10.1023/A:1005517326981

  View details for Web of Science ID 000088877400001

• Cognitive vulnerability for depression: Deployment of attention as a function of history of depression and current mood state COGNITIVE THERAPY AND RESEARCH McCabe, S. B., Gotlib, I. H., Martin, R. A. 2000; 24 (4): 427–44

  View details for DOI 10.1023/A:1005579719849

  View details for Web of Science ID 000088598800005

• Crying in depression Rottenberg, J., Najmi, S., Wilhelm, F. H., Gross, J. J., Gotlib, I. H. CAMBRIDGE UNIV PRESS. 2000: S83

  View details for Web of Science ID 000089900500339

• Cognitive functioning in depression: Nature and origins 1st Wisconsin Symposium on Emotion Gotlib, I. H., Gilboa, E., Sommerfeld, B. K. OXFORD UNIV PRESS. 2000: 133–163

  View details for Web of Science ID 000167657700007

• Information-processing approaches to the study of cognitive biases in depression 15th Symposium on Stress, Coping, and Depression Gotlib, I. H., Neubauer, D. L. LAWRENCE ERLBAUM ASSOC PUBL. 2000: 117–143

  View details for Web of Science ID 000085051900008

• Ethnic differences in the association between pubertal status and symptoms of depression in adolescent girls JOURNAL OF ADOLESCENT HEALTH Hayward, C., Gotlib, I. H., Schraedley, P. K., Litt, I. F. 1999; 25 (2): 143-149

  Abstract

  To examine the importance of chronologic age versus pubertal status in predicting adolescent girls' depressive symptoms in different ethnic groups.A national probability sample was used to obtain a representative cohort of 3216 adolescents, 5th through 8th grades. Subjects completed a questionnaire, which included a modified version of the Children's Depression Inventory (CDI) and an assessment of timing of menarche.Among Caucasians, post-menarcheal adolescent girls had higher depression scores than did same-aged pre-menarcheal girls. Boys and pre-menarcheal girls had similar depression scores in most age groups. Among African-Americans and Hispanics, there were no menarche-associated differences in depressive symptoms.In early adolescence pubertal status is a better predictor of depressive symptoms than chronological age in Caucasian, but not African-American or Hispanic girls.

  View details for Web of Science ID 000081723700008

  View details for PubMedID 10447041

• First onset versus recurrence of depression: Differential processes of psychosocial risk JOURNAL OF ABNORMAL PSYCHOLOGY Lewinsohn, P. M., Allen, N. B., Seeley, J. R., Gotlib, I. H. 1999; 108 (3): 483-489

  Abstract

  Differential risk factors for the onset of depression were prospectively examined in a community-based sample of adolescents (N = 1,709), some of whom had a history of major depressive disorder (MDD; n = 286) and some of whom did not (n = 1,423). From the theories of J. Teasdale (1983, 1988) and R. Post (1992) concerning the etiology of initial versus recurrent episodes of depression, the authors hypothesized that (a) dysphoric mood and dysfunctional thinking styles would be correlated more highly among those with a previous history of MDD than among those without a history of MDD; (b) dysphoric mood or symptoms and dysfunctional thinking would be a stronger predictor of onset of recurrent episodes (n = 43) than of first onsets (n = 70); and (c) major life stress would be a stronger predictor of first onsets of MDD than of recurrent episodes. The results provide support for the 3 hypotheses and suggest that distinct processes are involved in the onset of first and recurrent episodes of MDD.

  View details for Web of Science ID 000082120000013

  View details for PubMedID 10466272

• Gender differences in correlates of depressive symptoms in adolescents JOURNAL OF ADOLESCENT HEALTH Schraedley, P. K., Gotlib, I. H., Hayward, C. 1999; 25 (2): 98-108

  Abstract

  To determine: (a) what demographic and psychosocial factors are associated with elevated levels of depressive symptoms in adolescence; (b) whether girls and boys show different profiles of correlates and probable risk factors for depressive symptoms; and (c) what the implications are of these results for future research directions and policy decisions.Using a nationally representative sample of adolescent school students in Grades 5-12, the Commonwealth Fund Adolescent Health Survey assessed depressive symptoms as well as a number of variables posited to be risk factors and correlates of depression.Depressive symptoms were found to differ by gender, age, socioeconomic status, and ethnicity. In addition, life stress, social support, and coping were associated with depressive symptoms. Importantly, stress and social support appear to be particularly salient aspects of depression among girls. Both physical and sexual abuse were strongly linked with depression for both boys and girls, with sexual abuse having a stronger impact among boys. Finally, high levels of depressive symptoms were associated with increased use of both mental and physical health care resources among boys and girls.The correlates of depression in this adolescent sample closely resemble those seen in adult samples, including demographic and psychosocial variables. Some psychosocial variables, such as stress and social support, may have a greater impact on depressive symptoms for girls than for boys. Results of this study also have important implications for the health care system, given that higher levels of depressive symptoms were found to be associated with greater utilization of physical health care resources.

  View details for Web of Science ID 000081723700004

  View details for PubMedID 10447037

• Consequences of depression during adolescence: Marital status and marital functioning in early adulthood JOURNAL OF ABNORMAL PSYCHOLOGY Gotlib, I. H., Lewinsohn, P. M., Seeley, J. R. 1998; 107 (4): 686-690

  Abstract

  In previous studies, depression has been associated with both marital status and marital distress. Unfortunately, given the cross-sectional design of most of this research, the temporal nature of these associations is unclear. The authors examined the marital functioning of young adults as a function of whether they received psychiatric diagnoses of major depressive disorder or nonaffective psychiatric disorder during adolescence. Depression during adolescence was found to predict higher rates of marriage among younger women and subsequent marital dissatisfaction. This pattern of results appears to be specific to depression: The presence during adolescence of a nonaffective psychiatric disorder was unrelated to subsequent marital functioning. These findings highlight the potentially adverse consequences of depression in adolescence and underscore the importance of prevention and early treatment efforts.

  View details for Web of Science ID 000076987000016

  View details for PubMedID 9830257

• Biased information processing as a vulnerability factor for depression BEHAVIOR THERAPY Gotlib, I. H., Krasnoperova, E. 1998; 29 (4): 603-617

  View details for Web of Science ID 000077693800006

• Neuroticism and ruminative response style as predictors of change in depressive symptomatology COGNITIVE THERAPY AND RESEARCH Nolan, S. A., Roberts, J. E., Gotlib, I. H. 1998; 22 (5): 445-455

  View details for Web of Science ID 000077148300002

• Ruminative response style and vulnerability to episodes of dysphoria: Gender, neuroticism, and episode duration COGNITIVE THERAPY AND RESEARCH Roberts, J. E., Gilboa, E., Gotlib, I. H. 1998; 22 (4): 401-423

  View details for Web of Science ID 000075747000007

• Gender differences in anxiety disorders and anxiety symptoms in adolescents JOURNAL OF ABNORMAL PSYCHOLOGY Lewinsohn, P. M., Gotlib, I. H., Lewinsohn, M., Seeley, J. R., Allen, N. B. 1998; 107 (1): 109-117

  Abstract

  Gender differences in anxiety were examined in a large sample of adolescents that included 1,079 who had never met criteria for any disorder, 95 who had recovered from an anxiety disorder, and 47 who had a current anxiety disorder. Participants were examined on a wide array of psychosocial measures. There was a preponderance of females among current and recovered anxiety disorder cases, but not among those who had never experienced an anxiety disorder. The female preponderance emerges early in life, and retrospective data indicate that at age 6, females are already twice as likely to have experienced an anxiety disorder than are males. Psychosocial variables that were correlated with both anxiety and gender were identified. Statistically controlling for these variables did not eliminate the gender differences in prevalence or anxiety symptom means.

  View details for Web of Science ID 000072029400010

  View details for PubMedID 9505043

• Elevated self-standards and emotional distress during adolescence: Emotional specificity and gender differences COGNITIVE THERAPY AND RESEARCH Hankin, B. L., Roberts, J., Gotlib, I. H. 1997; 21 (6): 663-679

  View details for Web of Science ID 000071456200006

• Temporal variability in global self-esteem and specific self-evaluation as prospective predictors of emotional distress: Specificity in predictors and outcome JOURNAL OF ABNORMAL PSYCHOLOGY Roberts, J. E., Gotlib, I. H. 1997; 106 (4): 521-529

  Abstract

  Recent studies have found that temporal variability and reactivity in self-esteem (SE) are associated with risk for depressive symptoms subsequent to life stress. It is unclear, however, whether it is variability uniquely in SE that is critical, or whether variability in other domains, such as specific self-evaluation (SSE) and affect, would show similar effects. Further, the specificity of these effects to depression is unknown. In the present study, initially nondepressed women completed 7 daily ratings of SE, SSE, and affect. Over a 6-week prospective interval, the interactions of stressful life events and variability in both SE and SSE predicted changes in depression, particularly in individuals with more severe worst lifetime episodes of depressive symptoms. These effects were independent of average level of SE and SSE, as well as neuroticism and self-concept uncertainty. In contrast, variability in affect failed to predict changes in depression in interaction with life stress. Finally, none of the predictor variables interacted with stressful life events in predicting changes in anxiety.

  View details for Web of Science ID A1997YD32900003

  View details for PubMedID 9358682

• Cognitive biases and affect persistence in previously dysphoric and never-dysphoric individuals COGNITION & EMOTION Gilboa, E., Gotlib, I. H. 1997; 11 (5-6): 517-538

  View details for Web of Science ID A1997YG51300003

• Depression-related psychosocial variables: Are they specific to depression in adolescents? JOURNAL OF ABNORMAL PSYCHOLOGY Lewinsohn, P. M., Gotlib, I. H., Seeley, J. R. 1997; 106 (3): 365-375

  Abstract

  Although the psychosocial difficulties associated with adolescent depression are relatively well known, the extent to which these problems are specific to depression has received little attention. The authors examined the specificity to depression of a wide range of psychosocial variables in the following 3 groups of adolescents: depressed cases (n = 48), nonaffective disorder cases (n = 92), and never mentally ill participants (n = 1,079). The authors found 3 of the 44 variables assessed in this study to be strongly specific to depression, and only the depressed participants exhibited more problematic functioning than did the never mentally ill controls. Three variables are as follows: self-consciousness, self-esteem, and a reduction in activities because of physical illness or injury. Eight variables were more strongly associated with depression than with nonaffective disorder, and 8 variables characterized both depressed and nonaffective disorder adolescents. Implications of these findings for psychosocial theories of depression are discussed.

  View details for Web of Science ID A1997XM16100002

  View details for PubMedID 9241938

• Lifetime episodes of dysphoria: Gender, early childhood loss and personality BRITISH JOURNAL OF CLINICAL PSYCHOLOGY Roberts, J. E., Gotlib, I. H. 1997; 36: 195-208

  Abstract

  The roles of gender, early childhood loss and personality as risk factors for lifetime episodes of dysphoria were examined in a large sample of college students (N = 557). Dysphoria classifications were based on the Inventory to Diagnose Depression (IDD) and the IDD-Lifetime Version. Brief dysphoria was defined as meeting DSM-III-R symptom criteria for major depression without meeting the two-week duration criteria, whereas protracted dysphoria required that the duration criteria were also met. Although females reported higher levels of depressive symptoms and neuroticism than did males, and were more likely to have a lifetime history of episodes of dysphoria, males were more susceptible to the adverse effects of early childhood loss. Males with loss were more likely to have a history of protracted dysphoria and to report higher levels of neuroticism than were males who did not experience an early parental loss. Neuroticism, in turn, acted as a trait vulnerability characteristic to episodes of dysphoria in both males and females. Interestingly, the effects of gender on lifetime experience of dysphoria were mediated by neuroticism: females' increased vulnerability to episodes of dysphoria was due to their elevated levels of neuroticism.

  View details for Web of Science ID A1997WZ72700003

  View details for PubMedID 9167861

• The effects of induced and naturally occurring dysphoric mood on biases in self-evaluation and memory COGNITION & EMOTION Gilboa, E., Roberts, J. E., Gotlib, I. H. 1997; 11 (1): 65-82

  View details for Web of Science ID A1997WH20800004

• Distinguishing between state-dependent and non-state-dependent depression-related psychosocial variables BRITISH JOURNAL OF CLINICAL PSYCHOLOGY Rosenbaum, M., Lewinsohn, P. M., Gotlib, I. H. 1996; 35: 341-358

  Abstract

  The goals of this study were: (a) to determine which among a set of depression-related psychosocial variables are state-dependent; (b) to examine whether state-trait distinctions among psychosocial variables are a function of gender; and (c) to test the hypothesis that state-dependence of psychosocial variables is mostly evident in people with a history of clinical depression. Altogether, 562 participants residing in two communities completed a battery of psychosocial measures at point of entry into the study (T1) and after an average interval of 8.3 months (T2). The state-dependence of psychosocial variables was examined in two groups of participants: (a) low-high (LH: those who were low on the Center for Epidemiologic Studies Depression Scale at T1 and high at T2; N = 45); and (b) high-low (HL: those who were high at T1 and low at T2; N = 64). The following variables were found to be state-dependent: engagement in pleasant and unpleasant events; frequency of social contacts; dissatisfaction with oneself, one's neighborhood dwelling and one's friends; irrational beliefs, and positive and negative expectancies. In contrast, the following variables were not state-dependent: dissatisfaction with family and job, perception of control, and external attributions for positive and negative events. State-dependence was not moderated by age, gender or a history of depression. Possible explanations for why some variables are state-dependent and others are not state-dependent are offered.

  View details for Web of Science ID A1996VH73500002

  View details for PubMedID 8889076

• Adult attachment security and symptoms of depression: The mediating roles of dysfunctional attitudes and low self-esteem JOURNAL OF PERSONALITY AND SOCIAL PSYCHOLOGY Roberts, J. E., Gotlib, I. H., Kassel, J. D. 1996; 70 (2): 310-320

  Abstract

  Three studies investigated the relation between adult attachment security and symptoms of depression. Study l examined the overall magnitude of the association between adult attachment and depression, and Studies 2 and 3 tested whether this relation was mediated by dysfunctional attitudes and low self-esteem. Results from the three studies were consistent with a mediation model. This model suggests that insecure adult attachment styles are associated with dysfunctional attitudes, which in turn predispose to lower levels of self-esteem. Such depletions in self-esteem are directly associated with increases in depressive symptoms over time. Insecure attachment appears to lead to depressive symptoms in adulthood through its impact on self-worth contingencies and self-esteem.

  View details for Web of Science ID A1996TW05000009

  View details for PubMedID 8636884

• ADOLESCENT PSYCHOPATHOLOGY .4. SPECIFICITY OF PSYCHOSOCIAL RISK-FACTORS FOR DEPRESSION AND SUBSTANCE-ABUSE IN OLDER ADOLESCENTS JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY Lewinsohn, P. M., Gotlib, I. H., Seeley, J. R. 1995; 34 (9): 1221-1229

  Abstract

  To determine the specificity to major depressive disorder (MDD) of a wide array of psychosocial risk factors in older adolescents (aged 14 through 18 years).Diagnostic and psychosocial assessments were conducted with 1,507 randomly selected high school students at T1 and after approximately 1 year (T2). Three diagnostic groups were compared: those who had an episode of MDD during that year (n = 90), those who had an episode of substance use disorder during that year (SUD) (n = 42), and a control group with no disorder (n = 1,189).Risk factors specific to MDD were stress (minor and major events), emotional reliance, physical symptoms and disease, history of suicide attempt, and a past episode of depression or anxiety disorder. Risk factors specific to SUD were tobacco use, academic difficulties, and a past episode of SUD. Risk factors that were shared were current depression symptoms, internalizing and externalizing behavior problems, coping skills, interpersonal conflict with parents, and dissatisfaction with grades.By determining the number of risk factors for MDD, for SUD, or those that are general to both disorders, clinicians can make informed predictions concerning the probable future onset of a full-fledged episode of MDD and/or SUD in individual cases. The results of this study allow for the identification of adolescents who are at elevated risk for MDD and SUD. The results also have implications for the design of interventions aimed at preventing the occurrence of these disorders. Such interventions should target change on risk factors of the type identified in this study.

  View details for Web of Science ID A1995RR32300021

  View details for PubMedID 7559318

• LEVEL AND STABILITY OF SELF-ESTEEM AS PREDICTORS OF DEPRESSIVE SYMPTOMS PERSONALITY AND INDIVIDUAL DIFFERENCES Roberts, J. E., Kassel, J. D., Gotlib, I. H. 1995; 19 (2): 217-224

  View details for Web of Science ID A1995RJ69300010

• SYMPTOMS VERSUS A DIAGNOSIS OF DEPRESSION - DIFFERENCES IN PSYCHOSOCIAL FUNCTIONING JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY Gotlib, I. H., Lewinsohn, P. M., Seeley, J. R. 1995; 63 (1): 90-100

  Abstract

  In studies of clinical depression, individuals who demonstrate elevated levels of symptoms but do not meet interview-based diagnostic criteria are typically labeled as false positive and eliminated from further consideration. However, the implicit assumption that false-positive participants differ in important ways from true-positive (i.e., diagnosed) participants has not been tested systematically. This study compared the functioning of true-positive, false-positive, and true-negative adolescents on clinical and psychosocial functioning. Although the false-positive participants manifested higher levels of current and future psychopathology than did the true-negative participants, they did not differ significantly from the true-positive participants on most of the measures of psychosocial dysfunction. "False positive," therefore, is not a benign condition.

  View details for Web of Science ID A1995QG93600012

  View details for PubMedID 7896995

• ADOLESCENT PSYCHOPATHOLOGY .2. PSYCHOSOCIAL RISK-FACTORS FOR DEPRESSION JOURNAL OF ABNORMAL PSYCHOLOGY Lewinsohn, P. M., Roberts, R. E., Seeley, J. R., Rohde, P., Gotlib, I. H., Hops, H. 1994; 103 (2): 302-315

  Abstract

  In a prospective study of adolescent depression, adolescents (N = 1,508) were assessed at Time 1 and after 1 year (Time 2) on psychosocial variables hypothesized to be associated with depression. Most psychosocial variables were associated with current (n = 45) depression. Formerly depressed adolescents (n = 217) continued to differ from never depressed controls on many of the psychosocial variables. Many of the depression-related measures also acted as risk factors for future depression (n = 112), especially past depression, current other mental disorders, past suicide attempt, internalizing behavior problems, and physical symptoms. Young women were more likely to be, to become, and to have been depressed. Controlling for the psychosocial variables eliminated the gender difference for current and future but not for past depression.

  View details for Web of Science ID A1994NL11100014

  View details for PubMedID 8040500

• NEGATIVE COGNITIONS AND ATTRIBUTIONAL STYLE IN DEPRESSED ADOLESCENTS - AN EXAMINATION OF STABILITY AND SPECIFICITY JOURNAL OF ABNORMAL PSYCHOLOGY Gotlib, I. H., Lewinsohn, P. M., Seeley, J. R., Rohde, P., REDNER, J. E. 1993; 102 (4): 607-615

  Abstract

  Despite recent findings that the prevalence of unipolar depression is as high in adolescents as it is in adults, relatively little is known about the applicability of cognitive theories of depression to adolescents. The present study examined the nature, specificity, and stability of cognitive dysfunction in male and female depressed, remitted, and psychiatric control adolescents. Factor analysis of a diverse set of measures yielded two factors, labelled Negative Cognitions and Attributional Style. Scores on both these factors were related to a current diagnosis of depression. Results also indicated that there may not be complete recovery of cognitive functioning (or of depressed mood) with diagnostic remission of depression. Finally, whereas elevated scores on the Negative Cognitions factor appeared to be specific to depression, the depressed and psychiatric control adolescents did not differ with respect to their scores on the Attributional Style factor.

  View details for Web of Science ID A1993MF71900014

  View details for PubMedID 8282931