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

酒精使用表型和创伤后应激障碍：调查共同的遗传、行为和心理生理风险因素

• 批准号: 10583521
• 负责人: Kaitlin Elizabeth Bountress
• 金额: $ 17.07万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-03-01 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10583521
• 关键词: Alcohol Phenotype; Alcohol consumption; Alcohols; Behavioral; Big Data; Candidate Disease Gene; Clinical; Cognitive; Data; Data Analyses; Development; Disease; Environment; Epidemiologic Factors; Etiology; Frequencies; Funding; Generations; Genes; Genetic; Genetic Risk; Genomics; Goals; Laboratories; Laboratory Study; Linkage Disequilibrium; Longitudinal Studies; Maps; Measures; Mendelian randomization; Mental Health; Mentored Research Scientist Development Award; Mentorship; Methodology; Methods; Molecular; Molecular Genetics; National Institute on Alcohol Abuse and Alcoholism; Outcome; Pathway interactions; Patient Self-Report; Phenotype; Post-Traumatic Stress Disorders; Prevention; Process; Psyche structure; Psychiatric epidemiology; Psychophysiology; Research; Research Personnel; Research Priority; Risk; Risk Factors; Science; Social support; Socioeconomic Status; Stress; Testing; Time; Training; Translating; Translational Research; Trauma; Twin Multiple Birth; Work; alcohol risk; alcohol use disorder; anxiety sensitivity; anxiety symptoms; biobank; comorbidity; cost; design; distress tolerance; emotion regulation; experimental study; genetic association; genome wide association study; genomic data; improved; intervention program; low socioeconomic status; molecular scale; multidisciplinary; negative emotional state; non-genomic; novel; pleiotropism; polygenic risk score; psychiatric genomics; recruit; risk prediction; risk sharing; social; social epidemiology; trait; traumatic event; traumatic stress; university student

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.

项目摘要 创伤性事件很常见。创伤后应激障碍（PTSD）是一种最常见的 由创伤引起的疾病，倾向于与增加的酒精消耗共同发生（即，酒精量 x频率[AQF]）和AUD。许多关于PTSD和酒精表型共病的研究， 专注于PTSD-AUD。由于酒精消费量的增加与AUD有关，因此需要进行研究， 确定PTSD-AUD合并症的病因学过程是否与PTSD-AUD合并症的病因学过程相同， PTSD和AQF虽然这些表型的共同风险的途径尚不清楚， 纵向和实验研究表明，痛苦容忍（DT）的影响，感知能力， 承受负面情绪状态，焦虑敏感性（AS），认知评估焦虑症状， 对创伤后应激障碍和酒精表型产生有害的身体、精神或社会后果。此外，本发明还 PTSD和AQF/AUD的遗传影响可能是DT和AS的风险基础。因此，本K 01的目标 应用有三个方面：首先，拟议的研究将使用大规模的分子数据，并采用尖端的 研究PTSD-AQF和PTSD-AUD之间交叉表型预测的方法， PTSD与AQF/AUD的关系第二，本研究提出了研究DT之间的关联， 和AS，以及PTSD、AUD和PTSD-AUD共病的风险。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， 而社会支持会缓和这些影响。 为了实现这些目标，候选人将在其导师团队的协助下完成一项 一个全面的培训计划，映射到这三个目标。具体而言，此K 01应用程序将允许 候选人接受尖端遗传方法（培训目标1），基于实验室的范例和 心理生理学数据（培训目标2），与压力相关的精神和社会流行病学 表型（培训目标3）和专业发展（培训目标4）。的帮助下 多学科的指导团队，这个K 01奖将允许候选人整合大规模的遗传 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， 预测不同SES水平和不同社会支持者PTSD-AQF/AUD共病的风险。的 拟议的研究是在澄清这种昂贵的风险因素和机制方面迈出的重要一步。 共现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 了解并发PTSD和酒精表型的病因，以改善预防/干预 程序.这一目标符合NIAAA的主要研究重点，包括确定潜在的机制。 AUD和共同发生的心理健康问题，同时整合基因组和非基因组因素。