Neurodevelopmental Mechanisms linking Childhood Adversity with Adolescent Psychopathology: Pubertal Timing and Cortical-Limbic Circuitry

University Of Washington, Seattle WA

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Abstract

PROJECT SUMMARY (30 lines) Exposure to childhood adversity (CA) is associated with elevated risk for psychopathology. One consistently documented consequence of CA exposure in females is earlier age of pubertal onset. Early pubertal timing in females is also associated with elevated risk for mood and anxiety disorders?although the mechanisms through which early pubertal timing conveys risk for psychopathology are not well understood. In males, non- normative (i.e., early or late) pubertal timing is associated with risk for psychopathology, but associations of CA with pubertal timing in males have rarely been studied. Exposure to sex hormones at a non-normative age may alter neural development in ways that enhance vulnerability for adolescent psychopathology. However, scant research has examined how CA influences pubertal timing, how CA and pubertal timing impact brain development, and how these factors might ultimately contribute to risk for psychopathology. Even less research has examined whether and how these pathways might differ for males and females. The proposed studies address these gaps, with the goal of identifying mechanisms through which CA, pubertal timing, and brain development influence risk for psychopathology in adolescents. First, the proposed work will examine how different dimension of CA influence pubertal timing, in adolescent males and females. Second, we will investigate whether non-normative pubertal timing is a mechanism explaining the association between CA and psychopathology in adolescent males and females. Third, we will investigate whether pubertal timing-related changes in cortical-limbic circuitry mediate the association between CA and psychopathology in early adolescent females. Data will come from two samples. The first two aims will be examined in a large, nationally-representative sample of 6,483 adolescents aged 13-17 years who participated in in the National Comorbidity Survey-Adolescent Sample (NCS-A). This sample will allow us to investigate how different dimensions of CA influence pubertal timing and whether pubertal timing is a mechanism linking CA and psychopathology in adolescent males and females. The second sample comes from an ongoing longitudinal sample of 300 children followed annually from age 3 years. Data will be drawn from the most recent wave, at age 10-11 years where participants are completing fMRI scanning during a fear conditioning task. This study will permit examination of how alterations in pubertal timing and CA exposure impact cortical-limbic circuitry and, ultimately, adolescent psychopathology. The results of these studies will provide insight into the pathways through which CA, pubertal timing and brain development contribute to adolescent psychopathology. This award will provide the candidate, who has a strong background in clinical neuroscience in adolescence, with training in childhood adversity, pubertal development, and neurodevelopment models of adolescence to facilitate her transition to an independent research career.