Genetic and Environmental Risk/Resilience Factors for PTSD in OEF/OIF Veterans

描述(由申请人提供)： 研究保守估计，部署在伊拉克(伊拉克自由行动；OIF)和阿富汗(持久自由行动；OEF)战斗的军人中，有10%至20%的人在部署后出现严重的创伤后应激障碍(PTSD)症状。患有创伤后应激障碍的退伍军人面临着更多其他健康和心理健康问题的风险，并越来越多地向退伍军人健康管理局(VHA)提出护理。然而，并不是所有暴露在战斗中的退伍军人都有同样的可能性患上创伤后应激障碍。许多因素，包括环境和遗传因素及其相互作用，与创伤后应激障碍的风险/复原力有关。创伤后应激障碍的环境危险因素可分为创伤前因素、创伤相关因素和创伤后因素。在这些类别中，三个经过充分研究的风险因素是：1)创伤前接触不良/创伤事件的程度，包括儿童期虐待；2)创伤的严重程度/对生命威胁的看法；3)创伤后的社会支持。尽管我们知道创伤后应激障碍具有重要的可遗传成分，但关于导致创伤后应激障碍风险/弹性的特定基因变异的研究有限。在预测创伤后应激障碍方面，关于环境变量与遗传因素的潜在相互作用的可用数据甚至更少。然而，最近的几篇论文，包括我们团队的工作，已经确定了与环境因素(包括儿童期虐待、创伤暴露和社会支持)结合时，5-HTTLPR和FKBP5基因与环境因素一起预测创伤后应激障碍的风险/弹性的基因与环境的交互作用。这些基因是了解创伤后应激障碍风险的极佳候选基因，因为它们参与了压力反应，以及它们与情绪和其他焦虑症的症状和生物标记物之间的关联。大多数关于创伤后应激障碍的环境、遗传或基因x环境风险因素的研究集中在非战斗相关的创伤暴露上，更少的研究集中在最近回国的战斗老兵身上。拟议研究的目的是将上述关于创伤后应激障碍的环境、遗传和基因x环境预测因素的研究成果推广到N=800名战斗中暴露的OEF/OIF退伍军人(400人符合创伤后应激障碍诊断或有明显的创伤后应激障碍症状，400人不符合创伤后应激障碍诊断)，寻求VHA护理。此外，我们还在战斗相关心理社会压力任务和恐惧条件作用范式中预测创伤后应激障碍相关生物标记物时，包括了一个次要目标，重点是评估上述环境、遗传和基因x环境变量。我们的长期目标是结合对创伤后应激障碍风险/复原力的环境和遗传决定因素的了解，制定战略，以减轻风险因素并促进对创伤应激源的复原力，特别是在退伍军人等高危人群中。 公共卫生相关性： 在部署到伊拉克(伊拉克自由行动；OIF)和阿富汗(持久自由行动；OEF)作战的军人中，有10%-20%的人出现了严重的创伤后应激障碍(PTSD)症状。这些退伍军人越来越多地向退伍军人健康管理局(VHA)提出医疗保健，包括创伤后应激障碍治疗。患有创伤后应激障碍的退伍军人患上其他一些身体和心理健康问题的风险增加，包括自杀风险增加。然而，并不是所有暴露在战斗中的退伍军人都有同样的可能性患上创伤后应激障碍。该提案旨在研究OEF/OIF退伍军人患创伤后应激障碍的风险和复原力的遗传和环境决定因素。预计这些发现可能有助于减轻危险因素和提高对创伤应激源的适应能力。

DESCRIPTION (provided by applicant): Studies conservatively estimate that between 10 and 20% of military service members deployed to combat in Iraq (Operation Iraqi Freedom; OIF)) and Afghanistan (Operation Enduring Freedom; OEF) develop significant symptoms of Posttraumatic Stress Disorder (PTSD) post deployment. Combat veterans who develop PTSD are at increased risk for a number of additional health and mental health problems, and are increasingly presenting to the Veteran's Health Administration (VHA) for care. However, not all veterans exposed to combat are equally likely to develop PTSD. A number of factors, including environmental and genetic factors and their interaction, are associated with risk/resilience to PTSD. Environmental risk factors for PTSD can be categorized as: pre-trauma, trauma-related characteristics and post-trauma factors. Within these categories, three well studied risk factors are: 1) level of pre-trauma exposure to adverse/traumatic events, including childhood abuse 2) severity/perception of life threat of the trauma and 3) post trauma social support. Although we know that PTSD has a significant heritable component, research on the specific genetic variations conferring risk/resilience for PTSD is limited. There is even less available data on the potential interaction of environmental variables with genetic factors in the prediction of PTSD. However, several recent papers, including work from our groups, have identified gene by environment interactions predicting risk/resilience to PTSD for both the Serotonin Transporter Linked Polymorphism Region (5-HTTLPR) and the FKBP5 genes when in combination with environmental factors, including childhood abuse, traumatic exposure, and social support. These genes are excellent candidates for understanding risk for PTSD, both because of their involvement in the stress response, as well as their association, in prior research, with symptoms and biomarkers of mood and other anxiety disorders. The majority of the studies inclusive of environmental, genetic or gene x environment risk factors for PTSD focus on non-combat related trauma exposure, with even fewer focusing on recently returned combat veterans. The goal of the proposed study is to extend the above research findings on environmental, genetic and gene x environment predictors of PTSD to a population of N=800 combat exposed OEF/OIF veterans (400 meeting PTSD diagnosis or with significant symptoms of PTSD and 400 not meeting PTSD diagnosis) seeking VHA care. In addition, we have included a secondary aim focused on evaluating the above environmental, genetic, and gene x environment variables in predicting PTSD-related biomarkers in a combat-related psychosocial stress task and during a fear conditioning paradigm. Our long-term goal is to combine an understanding of the environmental and genetic determinants of risk/resilience to PTSD to develop strategies towards mitigating risk factors and promoting resilience to traumatic stressors, particularly in high-risk populations such as combat veterans. PUBLIC HEALTH RELEVANCE: Between 10 - 20% of military service members deployed to combat in Iraq (Operation Iraqi Freedom; OIF)) and Afghanistan (Operation Enduring Freedom; OEF) develop significant symptoms of Posttraumatic Stress Disorder (PTSD). These veterans are increasingly presenting to the Veteran's Health Administration (VHA) for health care, including PTSD treatment. Veterans who develop PTSD are at increased risk for a number of additional physical and mental health problems, including an increased risk for suicide. However, not all veterans exposed to combat are equally likely to develop PTSD. This proposal seeks to examine the genetic and environmental determinants of risk and resilience to PTSD in OEF/OIF combat veterans. It is anticipated that these findings may be helpful towards mitigating risk factors and promoting resilience to traumatic stressors.