Neurocognitive and genetic influences on post-traumatic stress and risky alcohol use in trauma-exposed adolescents and young adult offspring from families enriched with Alcohol Use Disorders

项目摘要 大约30%的人口在其一生中将符合酒精使用障碍（AUD）的标准， 使其成为美国最普遍的物质使用障碍。创伤后应激障碍 创伤后应激障碍（PTSD）是一种以在经历了一段时间的创伤后应激障碍后重新体验、回避和过度觉醒的症状为特征的病症。 创伤暴露，存在于大约6-8%的一般人群中，并且与 澳元。此外，具有AUD家族史的个体具有不成比例的高创伤率。 暴露和随后的PTSD和AUD与普通人群相比，这表明， 其他因素，包括遗传、社会环境和神经认知影响，可能会增加 创伤暴露、创伤后应激障碍和共同发生的AUD。然而，据我们所知， 已经研究了这些因素的影响，使用多个评估前瞻性衡量 整个青春期和青年期。我们假设，创伤暴露的青少年和年轻人 有AUD家族史的成年人患PTSD和/或合并AUD的风险高于创伤- 没有AUD家族史的暴露受试者，这些个体将表现出较低的认知效率， 功能（即，反应抑制）。此外，我们假设遗传风险变异影响 认知功能也可能影响PTSD和/或AUD的风险。我们将通过以下方式解决这些假设： 以下具体目的：1）检查创伤暴露和AUD家族史对以下风险的相互作用： 青少年和青年期的PTSD和共病AUD; 2）检查家庭的相互作用 反应抑制任务中AUD和创伤暴露史对神经认知功能和行为的影响 在青春期和青年期;和3）检查是否遗传风险变异影响神经认知 功能也会影响PTSD和/或AUD风险。来自遗传学合作研究的数据 酒精中毒（COGA）前瞻性研究（N= 3，812）将以2年为间隔（基线和3次随访）， 用于进行纵向分析，评估DSM-IV PTSD症状/诊断、酒精 依赖症状/诊断和神经认知功能。遗传变异符合重要性 认知基因组学联盟最近发表的全基因组关联研究中的标准（N= 35，298） 将检测与PTS和共病AUD风险的相关性。这项研究提案的结果可以 提供早期干预和治疗策略，旨在降低创伤后应激障碍的严重程度和持久性， 澳元。

PROJECT SUMMARY Approximately 30% of the population will meet criteria for an alcohol use disorder (AUD) in their lifetime, making it the most prevalent substance use disorder in the United States. Posttraumatic stress disorder (PTSD), a condition characterized by symptoms of re-experiencing, avoidance, and hyper-arousal following a traumatic exposure, is present in approximately 6-8% of the general population, and has high comorbidity with AUD. Additionally, individuals with a family history of AUD have a disproportionately high rate of trauma exposure and both subsequent PTSD and AUD as compared with the general population, which suggests that other factors, including genetic, social environmental, and neurocognitive influences, may increase the risk for trauma exposure, posttraumatic stress disorder, and co-occurring AUD. However, no study to our knowledge has examined the influence of these factors together, using multiple assessments prospectively measured throughout adolescence and young adulthood. We hypothesize that trauma-exposed adolescents and young adults with a family history of AUD will have a higher risk for later PTSD and/or comorbid AUD than trauma- exposed subjects without a family history of AUD, and that these individuals will show less efficient cognitive functioning (i.e., response inhibition). In addition, we hypothesize that genetic risk variants influencing cognitive function may also influence risk for PTSD and/or AUD. We will address these hypotheses through the following Specific Aims: 1) examine the interaction of trauma exposure and family history of AUD on risk for PTSD and comorbid AUD across adolescence and young adulthood; 2) examine the interaction of family history of AUD and trauma exposure on neurocognitive function and behavior during a response inhibition task across adolescence and young adulthood; and 3) examine if genetic risk variants influencing neurocognitive function also influence PTSD and/or AUD risk. Data from the Collaborative Study on the Genetics of Alcoholism (COGA) prospective study (N=3,812) at two-year intervals (baseline and 3 follow-ups) will be utilized to conduct longitudinal analyses assessing differences in DSM-IV PTSD symptoms/diagnosis, alcohol dependence symptoms/diagnosis, and neurocognitive functioning. Genetic variants meeting significance criteria in the Cognitive Genomics Consortium's recently published genome-wide association study (N=35,298) will be tested for association with risk for PTS and comorbid AUD. Findings from this research proposal could inform early intervention and treatment strategies aimed at reducing the severity and endurance of PTSD and AUD.