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  • 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

  • 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


    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

  • 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

  • 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

  • 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