Alcohol Use Phenotypes and Posttraumatic Stress Disorder: Investigating Shared Genetic, Behavioral, and Psychophysiological Risk Factors

项目摘要 创伤性事件很常见。创伤后应激障碍(PTSD)是最常见的 创伤引起的疾病往往与酒精消耗量增加(即酒精量)同时发生 X频率[AQF])和AUD。这项关于创伤后应激障碍和酒精表型共病的研究有很大一部分 重点关注创伤后应激障碍-澳大利亚疾病。由于酒精消耗量的增加与AUD相关，因此需要研究 确定PTSD-AUD共病背后的相同病因过程是否为潜在的 创伤后应激障碍和AQF。尽管这些表型的共同风险发生的途径尚不清楚， 纵向和实验研究表明，痛苦耐受性(DT)的影响，感知能力 耐受负面情绪状态，焦虑敏感度(AS)，焦虑症状的认知评估为 对创伤后应激障碍和酒精表型有有害的生理、心理或社会后果。另外， PTSD和AQF/AUD的遗传影响可能是DT和AS的风险基础。因此，这款K01的目标 应用有三个方面：第一，拟议的研究将使用大规模的分子数据并使用尖端技术 方法研究PTSD-AQF和PTSD-AUD之间的交叉表型预测和方向。 创伤后应激障碍与AQF/AUD的关系。第二，本研究建议调查DT和DT之间的关系 AS、PTSD、AUD和合并PTSD-AUD的风险。最后，通过一个探索性的目标，它将检查 AQF、AUD和PTSD的遗传风险是否与DT和AS相关，以及是否具有社会经济地位 而社会支持则缓和了这些影响。 为了实现这些目标，候选人将在她的指导团队的帮助下完成一项 与这三个目标对应的全面培训计划。具体地说，此K01应用程序将允许 接受尖端遗传方法(培训目标1)、以实验室为基础的范例和 心理生理学数据(培训目标2)，与压力有关的精神病学和社会流行病学 表型(培训目标3)和专业发展(培训目标4)。在世界银行 多学科导师团队，这个K01奖项将允许候选人整合大规模的基因 将研究结果与基于实验室的自我报告、行为和心理生理测量相关联，以 预测不同SES水平和不同社会支持的人同时发生PTSD-AQF/AUD的风险。这个 拟议的研究是在澄清这种代价高昂的风险因素和机制方面向前迈出的重要一步 同时发生的。候选人将接受培训的环境对候选人的长期目标来说是理想的 了解共患创伤后应激障碍和酒精表型的病因，以改进预防/干预 程序。这一目标与NIAAA的主要研究优先事项一致，涉及确定潜在的机制 在整合基因组和非基因组因素的同时，AUD和共生的精神健康问题。

Project Summary Traumatic events are common. Posttraumatic Stress Disorder (PTSD) is one of the most common disorders resulting from trauma, tending to co-occur with increased alcohol consumption (i.e., alcohol quantity x frequency [AQF]) and AUD. Much of this research on the comorbidity of PTSD and alcohol phenotypes has focused on PTSD-AUD. As increased consumption of alcohol is associated with AUD, research is needed to determine whether the same etiologic processes underlying PTSD-AUD comorbidity are those underlying PTSD and AQF. Although the pathways by which shared risk for these phenotypes unfolds is unclear, longitudinal and experimental research suggests effects of distress tolerance (DT), the perceived ability to withstand negative emotional states, and anxiety sensitivity (AS), cognitive appraisal of anxiety symptoms as having harmful physical, mental, or social consequences, on PTSD and alcohol phenotypes. Additionally, genetic influences on PTSD and AQF/AUD may underlie risk for DT and AS. Thus, the goals of this K01 application are threefold: First, the proposed study will use large-scale molecular data and employ cutting-edge methods to investigate cross phenotype prediction between PTSD-AQF, and PTSD-AUD, and direction of effect between PTSD and AQF/AUD. Second, this study proposes to investigate the associations between DT and AS, and risk for PTSD, AUD, and comorbid PTSD-AUD. Finally, via an Exploratory Aim, it will examine whether genetic risk for AQF, AUD, and PTSD are associated with DT and AS, and if socioeconomic status and social support moderate these effects. To achieve these aims, the candidate will be assisted by her mentorship team in the completion of a comprehensive training plan that maps onto these three goals. Specifically, this K01 application will allow the candidate to receive training in cutting edge genetic methods (training goal 1), laboratory-based paradigms and psychophysiological data (training goal 2), the psychiatric and social epidemiology of stress-related phenotypes (training goal 3), and professional development (training goal 4). With the help of the multidisciplinary mentorship team, this K01 award will allow the candidate to integrate large-scale genetic association findings with laboratory-based self-report, behavioral, and psychophysiological measures, to predict risk for PTSD-AQF/AUD co-occurrence for those of varying SES levels and varying social support. The proposed study represents an important step forward in clarifying risk factors and mechanisms of this costly co-occurrence. The environment where the candidate will be trained is ideal for the candidate's long-term goal of understanding the etiology of co-occurring PTSD and alcohol phenotypes to improve prevention/intervention programs. This goal is in line with key NIAAA's research priorities, involving identifying mechanisms underlying AUD and co-occurring mental health problems while integrating genomic and non-genomic factors.