The Impact of Adversity on Neurobiological and Psychosocial Dimensions of the Stress Response System

PROJECT SUMMARY/ABSTRACT Childhood adversity (CA) is one of the most potent risk factors for psychopathology across the lifespan, largely due to enduring disruptions in the body’s stress response system. Further, the cascade of molecular and neurobiological transformations following CA distinguishes patients from non-exposed counterparts, spurring a more pernicious course of illness, greater symptom severity, more comorbidities, and less favorable response to treatments. Thus, there is an urgent need to identify transdiagnostic mechanisms of risk. This proposal facilitates the long-term goal of identifying intervention targets, guided by evidence that adolescence is a period of vulnerability to stress that is accentuated by prior CA exposure. To date, investigations of neural, physiologic, and behavioral stress response deficits following CA have been conducted in relatively separate literatures, and the majority of these studies have taken a cumulative risk approach (i.e., “total adversity”) without attention to shared features among certain types of CA. Further, investigations of regulatory processes have generally examined either broad-level dysregulation or honed in on only regulatory strategy (e.g., reappraisal), neglecting to account for the dynamic nature of stress responsivity. This proposal addresses a critical gap in current research by examining a comprehensive set of stress responses, including emotion reactivity, emotion regulation (ER), and ER flexibility, each of which is a malleable target for intervention, spanning multiple units of analyses. Specifically, this study will examine CA characterized by threat (e.g., abuse, witnessing domestic violence), physiologic reactivity across multiple systems (i.e., HPA axis, parasympathetic and sympathetic branches of the autonomic nervous system), and neural activation during an fMRI paradigm that allows for an assessment of initial stress reactivity as well as ER strategy selection, implementation, and flexibility (i.e., evaluation and modification of a strategy based on the stressor/context). The sample will be comprised of 100 adolescents, aged 14-16 with varying levels of threat exposure. In addition to the initial assessment, participants will complete a six-month follow-up to measure prospective psychopathology symptoms, addressing a secondary focus of this proposal linking stress response patterns to internalizing and externalizing pathology. Employing a multi-unit analysis of acute stress responses will facilitate the characterization of precise CA-related decrements in reactivity and regulation that confer psychopathology risk during a crucial developmental period.