Trauma and Neurobiological Threat Reactivity as Risk Factors for Alcohol Abuse in Youth

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Underage drinking causes tremendous burden, and there is an urgent need to understand who is vulnerable, and why/how, to facilitate accurate detection and prevention. Exposure to interpersonal trauma (e.g., physical or sexual abuse) is a well-established risk factor for alcohol problems in youth; however, the developmental mechanisms through which trauma leads to alcohol use are unclear. In addition, millions of youth experience interpersonal trauma but only a subset develop alcohol use disorder (AUD). Identifying these high-risk youth, and the neurobiological mechanisms contributing to their risk, can pinpoint objective early intervention targets and aid in AUD prevention. Data from the Early Stage Investigator (ESI) PI suggests that youth with interpersonal trauma exposure and high levels of aversive reactivity to unpredictable threats (U-threat; temporally unpredictable and/or ambiguous) are at the greatest risk for the development of alcohol problems in young adulthood. To date, however, a mechanistic test of this hypothesis has never been conducted in a high-risk, trauma-exposed sample. The overarching goal of the study is to therefore validate a novel neurobiological risk phenotype for alcohol problems in trauma-exposed youth using multimodal U-threat reactivity data. Leveraging our unique access to high-risk youth in the central Ohio area, we will recruit a cohort of 200, 16-19 year olds, with and without a history of interpersonal trauma exposure (125 with trauma and 75 without) and conduct multimodal (neural function, physiology, behavior, and self-report) assessments of U-threat reactivity and alcohol use. Six months after baseline we will conduct a second multimodal lab assessment of U-threat reactivity. Every 3 months post-baseline we will assess youths’ alcohol use and relevant psychiatric symptoms and behaviors via online survey (up to 24-months). This innovative, longitudinal design will allow for a well-controlled test of whether interpersonal trauma exposure and neurobiological reactivity to U-threat synergistically interact to predict escalations in alcohol use in youth (Aim 1). The study will also address whether reactivity to U-threat is a stable risk factor for alcohol problems or a modifiable target that corresponds to changes in drinking behaviors over time (Aim 2). If reactivity to U-threat does indeed track behavior, it can be used as an objective, mechanistic target for future ‘Fast-Fail’ treatment studies. Lastly, given our multi-layered approach, we will conduct innovative analyses to integrate data across ‘units of analysis’ (brain, physiology, behavior, self-report) to predict the onset of alcohol problems in trauma- exposed youth and develop a new and replicable predictor with the highest accuracy performance (Aim 3). Findings from this work will provide critical new knowledge aiding in the identification of youth most at-risk for alcohol problems. The study will also validate a mechanistic, neurobiological risk model that identifies targets for intervention during a peak developmental risk window for alcohol use to ultimately help reduce the burden of AUD in this high-risk population.