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

未成年人饮酒造成了巨大的负担，迫切需要了解谁是弱势群体， 以及为什么/如何促进准确的检测和预防。暴露于人际创伤（例如，物理 或性虐待）是青年酗酒问题的一个公认的危险因素;然而， 创伤导致饮酒的机制尚不清楚。此外，数以百万计的年轻人 人际创伤，但只有一个子集发展为酒精使用障碍（AUD）。识别这些高危青少年， 以及导致其风险的神经生物学机制，可以确定客观的早期干预目标， 并有助于预防AUD。早期研究者（ESI）PI的数据表明， 人际创伤暴露和对不可预测威胁的高水平厌恶反应（U型威胁; 时间上不可预测和/或不明确）是酒精问题发展的最大风险 在年轻的成年期。然而，迄今为止，这一假设的机械测试从未在一个 高风险创伤暴露样本因此，这项研究的首要目标是验证一种新的 使用多模式U-威胁评估创伤暴露青年酒精问题的神经生物学风险表型 反应性数据利用我们在俄亥俄州中部地区接触高危青年的独特渠道，我们将招募一名 一组200名16-19奥尔兹的青少年，有或没有人际创伤暴露史（125名创伤患者）， 和75没有），并进行多模式（神经功能，生理，行为和自我报告）评估 对U型威胁的反应和酗酒基线后6个月，我们将进行第二次多模式实验室检查 U威胁反应性评估基线后每3个月，我们将评估青少年的酒精使用情况， 通过在线调查（长达24个月）了解相关精神症状和行为。这一创新， 纵向设计将允许一个良好的控制测试是否人际创伤暴露和 神经生物学反应U-威胁协同相互作用，以预测升级，在酒精使用的青年（目的 1）。该研究还将探讨对U-威胁的反应是否是酒精问题的稳定风险因素， 可修改的目标，对应于饮酒行为随时间的变化（目标2）。如果对U-威胁的反应性 确实跟踪行为，它可以作为一个客观的，机械的目标，为未来的'快速失败'治疗 问题研究最后，鉴于我们的多层次方法，我们将进行创新分析， “分析单位”（大脑，生理，行为，自我报告）来预测创伤中酒精问题的发生- 暴露的青年和开发一个新的和可复制的预测与最高的准确性性能（目标3）。 这项工作的结果将提供重要的新知识，帮助确定最有可能遭受暴力的青年。 酒精问题。这项研究还将验证一个机制，神经生物学风险模型，确定目标 在酒精使用的高峰发育风险窗口期进行干预，以最终帮助减轻负担， 在这一高风险人群中，

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.