Honors & Awards

  • Young Investigator Grant (NARSAD), The Brain and Behavior Research Foundation (2024-2026)

Stanford Advisors

All Publications

  • 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


    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

  • 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


    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


    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

  • Neighborhood disadvantage and parenting predict longitudinal clustering of uncinate fasciculus microstructural integrity and clinical symptomatology in adolescents. Developmental cognitive neuroscience Buthmann, J. L., Uy, J. P., Miller, J. G., Yuan, J. P., Coury, S. M., Ho, T. C., Gotlib, I. H. 2024; 66: 101368


    Parenting behaviors and neighborhood environment influence the development of adolescents' brains and behaviors. Simultaneous trajectories of brain and behavior, however, are understudied, especially in these environmental contexts. In this four-wave study spanning 9-18 years of age (N=224 at baseline, N=138 at final assessment) we used longitudinal k-means clustering to identify clusters of participants with distinct trajectories of uncinate fasciculus (UF) fractional anisotropy (FA) and anxiety symptoms; we examined behavioral outcomes and identified environmental factors that predicted cluster membership. We identified three clusters of participants: 1) high UF FA and low symptoms ("low-risk"); 2) low UF FA and high symptoms ("high-risk"); and 3) low UF FA and low symptoms ("resilient"). Adolescents in disadvantaged neighborhoods were more likely to be in the resilient than high-risk cluster if they also experienced maternal warmth. Thus, neighborhood disadvantage may confer neural risk for psychopathology that can be buffered by maternal warmth, highlighting the importance of considering multiple environmental influences in understanding emotional and neural development in youth.

    View details for DOI 10.1016/j.dcn.2024.101368

    View details for PubMedID 38547783

  • 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


    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

  • 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


    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

  • 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


    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

  • 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


    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

  • 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


    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

  • 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


    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

  • 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


    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

  • 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


    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

  • 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


    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

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


    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

  • Prenatal Exposure to a Climate-Related Disaster Results in Changes of the Placental Transcriptome and Infant Temperament. Frontiers in genetics Buthmann, J., Huang, D., Casaccia, P., O'Neill, S., Nomura, Y., Liu, J. 2022; 13: 887619


    Maternal stress during pregnancy exerts long-term effects on the mental well-being of the offspring. However, the long-term effect of prenatal exposure on the offspring's mental status is only partially understood. The placenta plays a vital role in connecting the maternal side to the fetus, thereby serving as an important interface between maternal exposure and fetal development. Here, we profiled the placental transcriptome of women who were pregnant during a hurricane (Superstorm Sandy), which struck New York City in 2012. The offspring were followed longitudinally and their temperament was assessed during the first 6-12months of age. The data identified a significant correlation between a Superstorm Sandy stress factor score and infant temperament. Further, analysis of the placental transcriptomes identified an enrichment of functional pathways related to inflammation, extracellular matrix integrity and sensory perception in the specimen from those infants with "Slow-to-Warm-up" temperament during the first year of life. Together, these findings provide initial evidence that maternal exposure to climate-related disasters results in altered placental transcriptome, which may be related to long-term emotional and behavioral consequences in children.

    View details for DOI 10.3389/fgene.2022.887619

    View details for PubMedID 35571026

  • 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


    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

  • Placental Gene Expression and Offspring Temperament Trajectories: Predicting Negative Affect in Early Childhood JOURNAL OF ABNORMAL CHILD PSYCHOLOGY Finik, J., Buthmann, J., Zhang, W., Go, K., Nomura, Y. 2020; 48 (6): 783-795


    Exposure to prenatal stress increases offspring risk for long-term neurobehavioral impairments and psychopathology, such as Attention Deficit Hyperactivity Disorder (ADHD). Epigenetic regulation of glucocorticoid pathway genes may be a potential underlying mechanism by which maternal conditions 'program' the fetal brain for downstream vulnerabilities. The present study aims to investigate whether mRNA expression of glucocorticoid pathway genes in the placenta predict offspring negative affect during early childhood (between 6 and 24 months). Participants include 318 mother-child dyads participating in a longitudinal birth cohort study. Placental mRNA expression of glucocorticoid pathway genes (HSD11B1, HSD11B2, NR3C1, NCOR2) were profiled and negative affect traits of the offspring were measured at 6, 12, 18, and 24 months. HSD11B1 mRNA expression significantly predicted negative affect (β = -.09, SE = .04; p = .036), and Distress to Limitations trajectories (β = -.13, SE = .06; p = .016). NCOR2 mRNA expression significantly predicted Distress to Limitations (β = .43, SE = .21; p = .047), and marginally predicted Sadness trajectories (β = .39, SE = .21; p = .068). HSD11B2 and NR3C1 did not predict trajectories of Negative Affect or subscale scores. Infant negative affect traits were assessed via maternal self-report, and deviated from linearity across follow-up. mRNA expression of glucocorticoid pathway genes in the placenta may be a potentially novel tool for early identification of infants at greater risk for elevated negative affect. Further study is needed to validate the utility of mRNA expression of glucocorticoid pathway genes in the placenta.

    View details for DOI 10.1007/s10802-020-00632-9

    View details for Web of Science ID 000520660800001

    View details for PubMedID 32185610

    View details for PubMedCentralID PMC7242121

  • The children of Superstorm Sandy: Maternal prenatal depression blunts offspring electrodermal activity BIOLOGICAL PSYCHOLOGY Buthmann, J., Finik, J., Ventura, G., Zhang, W., Shereen, A. D., Nomura, Y. 2019; 146: 107716


    We set out to examine the relations between prenatal exposure to the natural disaster Superstorm Sandy, maternal depression, and offspring electrodermal activity (EDA). EDA was measured via skin conductance response (SCR) magnitude in 198 children (M = 42.54 months, SD = 12.76) during a startle paradigm. In keeping with prior research, we expected prenatal depression to be associated with hyporeactive EDA and prenatal stress to be associated with hyperreactive EDA. SCR magnitude was lower in children prenatally exposed to depression alone, when compared to Superstorm Sandy, and controls. SCR magnitude of children prenatally exposed to both maternal depression and the storm was lower than that of all other groups. Our results emphasize the influence of maternal prenatal mental health, support targeted risk assessment for children who experienced an adverse prenatal environment, and highlight the need for a deeper understanding of the interactions between maternal mood and stress on the developing child.

    View details for DOI 10.1016/j.biopsycho.2019.107716

    View details for Web of Science ID 000485784700010

    View details for PubMedID 31176750

    View details for PubMedCentralID PMC6718305

  • Influence of in utero exposure to maternal depression and natural disaster-related stress on infant temperament at 6 months: The children of Superstorm Sandy INFANT MENTAL HEALTH JOURNAL Nomura, Y., Davey, K., Pehme, P. M., Finik, J., Glover, V., Zhang, W., Huang, Y., Buthmann, J., Dana, K., Yoshida, S., Tsuchiya, K. J., Li, X., Ham, J. 2019; 40 (2): 204-216


    This study examined the effects of in utero exposure to maternal depression and Superstorm Sandy, a hurricane that hit metropolitan New York in 2012, on infant temperament at 6 months. Temperament was assessed using the Infant Behavior Questionnaire-Revised. Maternal depression was measured by the Edinburgh Postnatal Depression Scale. The main effects and the interaction of maternal depression and Sandy exposure on infant temperament were examined using a multivariable generalized linear model. Results show that prenatal maternal depression was associated with lower emotion regulation and greater distress. Stratification and interaction analyses suggested that the adverse effects of prenatal maternal depression on problematic temperament were amplified by in utero Sandy exposure. This study underscores the importance of providing prenatal screening and treatment for maternal depression during pregnancy while also identifying high-risk families who may have suffered from disaster-related traumas to provide necessary services. As the frequency of natural disasters may increase due to climate change, it is important to understand the consequences of in utero stress on child development and to formulate plans for early identification.

    View details for DOI 10.1002/imhj.21766

    View details for Web of Science ID 000461054900003

    View details for PubMedID 30723931

    View details for PubMedCentralID PMC6491203

  • Infant Temperament: Repercussions of Superstorm Sandy-Related Maternal Stress CHILD PSYCHIATRY & HUMAN DEVELOPMENT Buthmann, J., Ham, J., Davey, K., Finik, J., Dana, K., Pehme, P., Zhang, W., Glover, V., Nomura, Y. 2019; 50 (1): 150-162


    This study recruited a prospective cohort of 380 pregnant women before, during, or after Superstorm Sandy in 2012 to examine the association between disaster-related pre- and post-natal maternal stress and offspring temperament at 6 months-old. Mothers prospectively reported stressful experiences during the storm and rated their child's temperament 6 months postpartum. Results indicated that length of time without phone or electricity and financial loss was associated with offspring negative affect, whereas financial loss and threat of death or injury was associated with emotion dysregulation. Furthermore, offspring born before the storm had greater negative affect and lower emotion regulation than those born after the storm. Given the probable increase in the occurrence of natural disasters due to climate change in recent years (McCarthy, Intergovernmental Panel on Climate Change, Climate change 2001: impacts, adaptation, and vulnerability: contribution of Working Group II to the third assessment report of the Intergovernmental Panel on Climate Change, Cambridge University Press, Cambridge, 2001), our results highlight the necessity of education and planning to help ameliorate any potential consequences on the developing infant.

    View details for DOI 10.1007/s10578-018-0828-2

    View details for Web of Science ID 000458372000014

    View details for PubMedID 30030653

    View details for PubMedCentralID PMC6339835

  • Sex differences in the relations between infant temperament and electrodermal responses in early childhood INTERNATIONAL JOURNAL OF BEHAVIORAL DEVELOPMENT Buthmann, J., Finik, J., Nomura, Y. 2018; 42 (6): 535-542


    The present study examines the relationship between sex, infant temperament, and childhood psychophysiological reactivity via electrodermal activity (EDA). Both temperament and EDA are known to be relatively stable traits across the lifespan reflecting individual reactivity and regulation linked to suboptimal behavioral development and risk for psychopathology. However, little is known about the role of sex in the relationship between temperament and EDA. As a part of a larger longitudinal study of behavioral development, 125 participants were followed from birth till 3 years-old to examine the relationship between temperament and psychophysiological reactivity in different gender groups. Measurements of temperament at 6 months-old, and EDA, via skin conductance response (SCR) rate to a series of six startling auditory stimuli at 3 years-old were collected. Median splits of SCR scores and three temperament dimensions (positive affect, negative affect, and regulation) were created to designate high/low groups. Results indicate sex moderated the relationships between temperament traits and SCR rates. Specifically, low positive affect was associated with an increased risk for high psychophysiological reactivity in boys (odds ratio = 3.8), whereas high regulation was associated with an increased risk for greater reactivity in girls (odds ratio = 4.2). While preliminary, these findings suggest the importance of sex in relation to psychophysiological and temperamental reactivity, risk factors for developmental psychopathology. As our participants age, follow-up research to investigate the stability of these associations will provide valuable insights for the potential of EDA as a psychophysiological marker for developmental psychopathology risk in young children.

    View details for DOI 10.1177/0165025418757705

    View details for Web of Science ID 000452308400002

    View details for PubMedID 31105363

    View details for PubMedCentralID PMC6516783

  • Prenatal exposure to disaster-related traumatic stress and developmental trajectories of temperament in early childhood: Superstorm Sandy pregnancy study JOURNAL OF AFFECTIVE DISORDERS Zhang, W., Rajendran, K., Ham, J., Finik, J., Buthmann, J., Davey, K., Pehme, P. M., Dana, K., Pritchett, A., Laws, H., Nomura, Y. 2018; 234: 335-345


    Little is known about the impact of prenatal maternal stress (PNMS) on the developmental trajectory of temperament and few studies have been able to incorporate a natural disaster as a quasi-experimental stressor. The current study investigated PNMS related to Superstorm Sandy ('Sandy'), a hurricane that struck the New York metropolitan area in October 2012, in terms of objective exposure during pregnancy, subjective stress reaction as assessed by maternal symptoms of post-traumatic stress, and their impact on the developmental changes in temperament during early childhood.A subsample of 318 mother-child dyads was drawn from the Stress in Pregnancy Study. Temperament was measured at 6, 12, 18, and 24 months of age.Objective exposure was associated with greater High-Intensity Pleasure, Approach, Perceptual Sensitivity and Fearfulness, but lower Cuddliness and Duration of Orientation at 6 months. Objective exposure and its interaction with subjective stress reaction predicted developmental changes in temperament. In particular, objective exposure was linked to greater increases in Activity Level but decreases in High-Intensity Pleasure, Approach, and Fearfulness. The combination of objective exposure and subjective stress reaction was also associated with greater increases in Activity Level.Temperament was measured solely via maternal report. Trimester-specific effects of Sandy on temperament were not examined.This is the first study to examine the effects of prenatal maternal exposure to a natural disaster on trajectories of early childhood temperament. Findings suggest that both objective stress exposure and subjective stress reaction in-utero predict developmental trajectories of temperament in early childhood.

    View details for DOI 10.1016/j.jad.2018.02.067

    View details for Web of Science ID 000429308000049

    View details for PubMedID 29614461

    View details for PubMedCentralID PMC5963732

  • Placental MAOA expression mediates prenatal stress effects on temperament in 12-month-olds INFANT AND CHILD DEVELOPMENT Pehme, P. M., Zhang, W., Finik, J., Pritchett, A., Buthmann, J., Dana, K., Hao, K., Nomura, Y. 2018; 27 (4)


    The placenta adapts to maternal environment and its alterations may have a lasting impact on child's temperament development. Prenatal stress has been linked to both a downregulation of monoamine oxidase A (MAOA) gene expression in the placenta and to difficult temperament. Capitalizing on an ongoing longitudinal study, we analysed data from 95 mother-child dyads to investigate whether MAOA mediates the association between prenatal stress and infant temperament. Prenatal stress was defined as exposure to Superstorm Sandy (Sandy) during pregnancy. Infant temperament was measured by Infant Behaviour Questionnaire-Revised. MAOA gene expression was quantified in placenta tissue. The Smiling and Laughter subscale score was independently associated with Sandy exposure and MAOA placental gene expression. Mediation analysis confirmed that MAOA expression partially mediated the relationship between Sandy and Smiling and Laughter subscale, suggesting that in utero exposure to Sandy could induce lower frequency of smiling and laughter via downregulation of placental MAOA gene expression. These effects could compromise optimal temperamental trajectory and contribute to risk for psychological problems. Placental epigenetic markers can contribute to a multidimensional model of early intervention for high-risk children.

    View details for DOI 10.1002/icd.2094

    View details for Web of Science ID 000440923300011

    View details for PubMedID 30505241

    View details for PubMedCentralID PMC6261505

  • Timing of prenatal exposure to trauma and altered placental expressions of hypothalamic-pituitary-adrenal axis genes and genes driving neurodevelopment JOURNAL OF NEUROENDOCRINOLOGY Zhang, W., Li, Q., Deyssenroth, M., Lambertini, L., Finik, J., Ham, J., Huang, Y., Tsuchiya, K. J., Pehme, P., Buthmann, J., Yoshida, S., Chen, J., Nomura, Y. 2018; 30 (4): e12581


    Prenatal maternal stress increases the risk for negative developmental outcomes in offspring; however, the underlying biological mechanisms remain largely unexplored. In the present study, alterations in placental gene expression associated with maternal stress were examined to clarify the potential underlying epi/genetic mechanisms. Expression levels of 40 selected genes involved in regulating foetal hypothalamic-pituitary-adrenal axis and neurodevelopment were profiled in placental tissues collected from a birth cohort established around the time of Superstorm Sandy. Objective prenatal traumatic stress was defined as whether mothers were exposed to Superstorm Sandy during pregnancy. Among the 275 mother-infant dyads, 181 dyads were delivered before Superstorm Sandy (ie, Control), 66 dyads were exposed to Superstorm Sandy during the first trimester (ie, Early Exposure) and 28 were exposed to Superstorm Sandy during the second or third trimester (ie, Mid-Late Exposure). Across all trimesters, expression of HSD11B2, MAOA, ZNF507 and DYRK1A was down-regulated among those exposed to Superstorm Sandy during pregnancy. Furthermore, trimester-specific differences were also observed: exposure during early gestation was associated with down-regulation of HSD11B1 and MAOB and up-regulation of CRHBP; exposure during mid-late gestation was associated with up-regulation of SRD5A3. The findings of the present study suggest that placental gene expression may be altered in response to traumatic stress exposure during pregnancy, and the susceptibility of these genes is dependent on the time of the exposure during pregnancy. Further studies should aim to clarify the biological mechanisms that underlie trimester-specific exposure by evaluating the differential impact on offspring neurodevelopment later in childhood.

    View details for DOI 10.1111/jne.12581

    View details for Web of Science ID 000430917800003

    View details for PubMedID 29423924

    View details for PubMedCentralID PMC5939590

  • Neurodevelopmental consequences in offspring of mothers with preeclampsia during pregnancy: underlying biological mechanism via imprinting genes ARCHIVES OF GYNECOLOGY AND OBSTETRICS Nomura, Y., John, R. M., Janssen, A., Davey, C., Finik, J., Buthmann, J., Glover, V., Lambertini, L. 2017; 295 (6): 1319-1329


    Preeclampsia is known to be a leading cause of mortality and morbidity among mothers and their infants. Approximately 3-8% of all pregnancies in the US are complicated by preeclampsia and another 5-7% by hypertensive symptoms. However, less is known about its long-term influence on infant neurobehavioral development. The current review attempts to demonstrate new evidence for imprinting gene dysregulation caused by hypertension, which may explain the link between maternal preeclampsia and neurocognitive dysregulation in offspring.Pub Med and Web of Science databases were searched using the terms "preeclampsia," "gestational hypertension," "imprinting genes," "imprinting dysregulation," and "epigenetic modification," in order to review the evidence demonstrating associations between preeclampsia and suboptimal child neurodevelopment, and suggest dysregulation of placental genomic imprinting as a potential underlying mechanism.The high mortality and morbidity among mothers and fetuses due to preeclampsia is well known, but there is little research on the long-term biological consequences of preeclampsia and resulting hypoxia on the fetal/child neurodevelopment. In the past decade, accumulating evidence from studies that transcend disciplinary boundaries have begun to show that imprinted genes expressed in the placenta might hold clues for a link between preeclampsia and impaired cognitive neurodevelopment. A sudden onset of maternal hypertension detected by the placenta may result in misguided biological programming of the fetus via changes in the epigenome, resulting in suboptimal infant development.Furthering our understanding of the molecular and cellular mechanisms through which neurodevelopmental trajectories of the fetus/infant are affected by preeclampsia and hypertension will represent an important first step toward preventing adverse neurodevelopment in infants.

    View details for DOI 10.1007/s00404-017-4347-3

    View details for Web of Science ID 000401337700004

    View details for PubMedID 28382413

    View details for PubMedCentralID PMC6058691