Threat-Related Negative Valence Systems, Child Victimization, and Anxiety

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Interpersonal violence (IPV) exposure affects 1 in 2 youth and levies tremendous physical and mental health burdens on victims and society. Childhood IPV exposure is a well-established risk factor for anxiety and other mental health problems across the lifespan. There is great variability among youth in the nature and timing of IPV exposure and considerable heterogeneity in mental health outcomes. Such heterogeneity in outcomes may be explained by various Research Domain Criteria (RDoC) constructs, including Negative Valence Systems (NVS) involving responses to threat. That is, disruptions in the functioning and development of neural and physiological systems associated with threat processing may account for heightened anxiety symptoms commonly observed following IPV. A paucity of longitudinal studies assessing multiple threat-related mechanisms, across multiple units of analysis, and at key times in development has been a critical barrier to informing the design of personalized treatments to target root causes of post-IPV psychopathology. The overarching goal of this project is to examine developmental trajectories of threat-related NVS measures into adolescence, as a function of exposure to IPV, in an effort to better link IPV and anxiety through changes in these measures. The specific aims of this project are: 1) to identify threat-related NVS constructs that connect lifetime IPV to anxious symptoms in youth cross-sectionally; 2) to investigate longitudinally the degree to which IPV sensitizes trajectories of NVS measures over a two-year period across three age cohorts (grades 3, 6, 9 at baseline); and 3) to investigate the degree to which trajectories of NVS measures predict anxiety symptoms over a 2-year period after accounting for initial anxiety symptoms and IPV status. An exploratory aim is to examine how amygdala activity and ACC functioning at baseline and overtime predict changes in other threat- related NVS measures (ERP, startle, ERN, cortisol reactivity) over time. To accomplish the aims, the approach involves studying the contributions of three threat-related NVS constructs, including responses to acute threat, potential threat, and sustained threat. These constructs will be measured across multiple units of analysis (neural circuitry, physiology, behavior/self-report) and over time using a battery of well-validated translational neuroscience laboratory paradigms and assessment tools. An accelerated longitudinal cohort design will be used to test key developmental questions (e.g., whether pubertal status moderates the effect of IPV on potential threat or sustained threat). Three cohorts of children (total n=360) and their caregivers will be enrolled and prospectively across 3 annual in-person lab assessments, with phone-based assessments in between. A community sample representing a broad continuum of IPV experiences and a wide range of anxiety symptoms will be recruited. By studying multiple NVS constructs over time across multiple units of analysis, findings will clarify the timing and developmental course of psychobiological vulnerabilities to anxiety problems in IPV- exposed youth, and will impact clinical care and future clinical research classification.