All Publications

  • 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
  • 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


    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

  • 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
  • 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
  • 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

  • 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
  • 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
  • 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


    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

  • 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: 1–12


    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

  • 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
  • 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


    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

  • 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


    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


    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


    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


    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
  • Perceptions of Resilience and Physical Health Symptom Improvement Following Post Disaster Integrated Health Services. Disaster medicine and public health preparedness Osofsky, H. J., Weems, C. F., Graham, R. A., Osofsky, J. D., Hansel, T. C., King, L. S. 2018: 1–7


    Theorists and researchers have linked resilience with a host of positive psychological and physical health outcomes. This paper examines perceptions of resilience and physical health symptoms in a sample of individuals exposed to multiple community disasters following involvement in integrated mental health services.A multiwave naturalistic design was used to follow 762 adult clinic patients (72% female; 28% minority status), ages 18-92 years (mean age=40 years), who were evaluated for resilience and physical health symptoms prior to receiving services and at 1, 3, and 6 months' follow-up.Data indicated increases in perceptions of resilience and decreased physical health symptoms reported over time. Results also indicated that resilience predicted physical health symptoms, such that resilience and physical health symptoms were negatively associated (ie, improved resilience was associated with decreases in physical health symptoms). These effects were primarily observed for those individuals with previous exposure to natural disasters.Findings provide correlational evidence for behavioral health treatment provided as part of a stepped-care, collaborative model in reducing physical health symptoms and increasing resilience post-disaster. Controlled trials are warranted. (Disaster Med Public Health Preparedness. 2018;page 1 of 7).

    View details for PubMedID 29916794

  • 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


    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

  • 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


    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

  • 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


    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

  • Perceptions of Trauma and Loss among Children and Adolescents Exposed to Disasters a Mixed-Methods Study CURRENT PSYCHOLOGY King, L. S., Osofsky, J. D., Osofsky, H. J., Weems, C. F., Hansel, T. C., Fassnacht, G. M. 2015; 34 (3): 524-536