1 of 2 - Prospective Determination of Psychobiological Risk Factors for PTSD

描述（由申请人提供）：创伤后应激障碍（PTSD）是最普遍的精神障碍之一，由于自然灾害（地震、飓风、海啸）、人为灾难（石油泄漏）、恐怖主义和战争以及暴力犯罪和汽车事故的数量不断增加，其患病率可能在美国和世界范围内增加。虽然大多数创伤受害者的主要症状是重新体验、逃避和过度觉醒，但对大多数这样的人来说，这些症状不会变成慢性的，也不会发展成创伤后应激障碍综合征。由于与PTSD相关的医学和精神疾病的发病率和死亡率非常高，因此确定少数极有可能发展为PTSD的创伤受害者是很重要的。已经有相当多的证据表明，创伤暴露后发生PTSD的可能性是遗传和环境因素共同作用的结果。这两个位点，链接的R-01应用程序寻求利用最先进的基因组学，转录组学和表观遗传学，结合全面的临床和心理测量，解决创伤后应激障碍临床服务和研究中这个开创性的未解之谜。为了实现这一目标，将在迈阿密大学莱德创伤中心和埃默里大学附属格雷迪纪念医院招募500名创伤暴露的受试者，并定期随访一年。这个集中的，假设驱动的研究将仔细审查以前

DESCRIPTION (provided by applicant): Post-traumatic Stress Disorder (PTSD) is one of the most highly prevalent psychiatric disorders and its prevalence is likely increasing in the United States and worldwide due to the rising numbers of natural disasters (earthquakes, hurricanes, tsunamis), man-made disasters (oil spills), terrorism and wars, as well as violent crime and automobile accidents. Although the majority of trauma victims experience the cardinal symptoms of re-experiencing, avoidance and hyperarousal, for the large majority of such individuals, these symptoms do not become chronic nor do they develop syndromal PTSD. It is important to identify the large minority of trauma victims with a high likelihood of developing PTSD because of the very significant medical and psychiatric morbidity and mortality associated with this disorder. There is already considerable evidence that the likelihood of developing PTSD after trauma exposure is due to a combination of genetic and environmental factors. This two-site, linked R-01 application seeks to utilize state-of-the art advances in genomics, transcriptomics and epigenetics, coupled with comprehensive clinical and psychological measures, to address this seminal unanswered question in PTSD clinical service and research. To achieve this goal, 500 trauma-exposed subjects will be recruited at the University of Miami Ryder Trauma Center and the Emory University affiliated Grady Memorial Hospital and followed at regular intervals for one year. This focused, hypothesis-driven study will scrutinize previously identified psychological and biological risk factors. Genetic risk factors include polymorphisms of the ADCYAP1R1, FKBP5, DAT, BDNF, COMT, CRFR1, 5HTTLPR, RGS2, GABA2 and 5HT3R genes, novel genetic and epigenetic risk factors and most importantly, the primary downstream effects of these genomic and epigenetic findings by the use of conventional and newer statistical modeling methods. These findings should provide the means to identify trauma survivors who will likely develop PTSD and can therefore be referred for appropriate psychotherapeutic and/or psychopharmacologic treatment. Such a strategy has the potential to help redefine psychobiological subtypes of PTSD as well as to reduce the burden of chronic PTSD on our healthcare system.