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，部署到伊拉克（伊拉克自由行动; OIF）和阿富汗（持久自由行动; OEF）的军事服务人员中有10%至20%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许多额外的健康和心理健康问题的风险增加，并且越来越多地向退伍军人健康管理局（VHA）提出护理。然而，并不是所有经历过战斗的退伍军人都同样有可能患上PTSD。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/恢复力有关。PTSD的环境危险因素可分为：创伤前、创伤相关特征和创伤后因素。在这些类别中，三个研究充分的风险因素是：1）创伤前暴露于不良/创伤事件的水平，包括儿童期虐待，2）创伤的严重程度/对生命威胁的感知，3）创伤后社会支持。虽然我们知道PTSD具有显著的遗传成分，但对赋予PTSD风险/恢复力的特定遗传变异的研究有限。关于环境变量与遗传因素在预测PTSD中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，包括我们小组的工作，已经确定了基因与环境的相互作用，预测5-HTTLPR和FKBP 5基因与环境因素（包括儿童虐待，创伤暴露和社会支持）相结合时对PTSD的风险/恢复力。这些基因是了解PTSD风险的绝佳候选者，因为它们参与了压力反应，以及它们在先前研究中与情绪和其他焦虑症的症状和生物标志物的关联。大多数研究包括环境，遗传或基因x环境风险因素的PTSD集中在非战斗相关的创伤暴露，更少的关注最近返回的战斗退伍军人。拟议研究的目标是将上述关于PTSD的环境、遗传和基因x环境预测因子的研究结果扩展到寻求VHA护理的N=800名战斗暴露OEF/OIF退伍军人（400名符合PTSD诊断或有显著PTSD症状，400名不符合PTSD诊断）。此外，我们还纳入了一个次要目标，重点是评估上述环境、遗传和基因x环境变量，以预测与战斗相关的心理社会应激任务和恐惧条件反射范式中的PTSD相关生物标志物。我们的长期目标是将对PTSD风险/恢复力的环境和遗传决定因素的理解联合收割机，以制定减轻风险因素和促进对创伤压力源的恢复力的策略，特别是在高危人群中，如退伍军人。 公共卫生相关性： 在伊拉克（伊拉克自由行动; OIF）和阿富汗（持久自由行动; OEF）部署战斗的军事服务人员中，有10 - 20%会出现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面临着许多其他身心健康问题的风险增加，包括自杀风险增加。然而，并不是所有经历过战斗的退伍军人都同样有可能患上PTSD。该提案旨在研究OEF/OIF战斗退伍军人中PTSD风险和恢复力的遗传和环境决定因素。预计这些发现可能有助于减轻风险因素和促进对创伤压力源的恢复力。

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.