2 of 2 Prospective Determination of Psychobiological Risk Factors for PTSD

描述(申请人提供)：创伤后应激障碍(PTSD)是最普遍的精神疾病之一，由于自然灾害(地震、飓风、海啸)、人为灾难(漏油)、恐怖主义和战争以及暴力犯罪和汽车事故的增加，其在美国和世界范围内的流行率可能会增加。虽然大多数创伤受害者经历了重新经历、回避和高度唤醒的主要症状，但对于绝大多数这样的人来说，这些症状不会成为慢性症状，也不会发展为综合征性创伤后应激障碍。由于与创伤后应激障碍相关的医疗和精神疾病的发病率和死亡率非常高，因此必须确定极有可能患上创伤后应激障碍的少数创伤受害者。已经有相当多的证据表明，创伤暴露后患上创伤后应激障碍的可能性是遗传和环境因素共同作用的结果。这一两个站点的关联R-01应用程序寻求利用基因组学、转录学和表观遗传学方面的最新进展，以及全面的临床和心理措施，来解决创伤后应激障碍临床服务和研究中这一开创性的悬而未决的问题。为了实现这一目标，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将招募600名创伤暴露受试者，并定期跟踪观察一年。这项以假设为导向的重点研究将仔细审视之前 确定了心理和生物风险因素。遗传风险因素包括基因多态 ADCYAP1R1、FKBP5、DAT、BDNF、COMT、CRFR1、5HTTLPR、RGS2、GABA2和5HT3R基因，新的遗传和表观遗传危险因素，以及最重要的是，这些基因组和表观遗传发现的主要下游效应，通过使用传统和新的统计建模方法。这些发现应该提供了识别创伤幸存者的手段，这些幸存者可能会患上创伤后应激障碍，因此可以转介给他们进行适当的心理治疗和/或精神药理治疗。这样的策略有可能帮助重新定义创伤后应激障碍的心理生物学亚型，并减轻慢性创伤后应激障碍对我们医疗系统的负担。 公共卫生相关性：不幸的是，严重创伤在美国和世界各地非常普遍，因此创伤后应激障碍(PTSD)的患病率是最常见的严重严重精神障碍之一。该领域尚未回答的根本问题是如何在创伤受害者中识别预测谁后来会患上创伤后应激障碍的标志物。有能力确定那些有很大可能患上创伤后应激障碍的人，将有助于制定能够适当和有效地实施的预防性干预战略。

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, 600 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. PUBLIC HEALTH RELEVANCE: Exposure to severe trauma is, unfortunately, extraordinarily common in the United States and worldwide, and consequently the prevalence rate of posttraumatic stress disorder (PTSD) is among the most common of the severe major psychiatric disorders. The fundamental unanswered question in the field is how to identify markers in trauma victims that predict who will later develop PTSD. The ability to identify those individuals with a high likelihood of developing PTSD will permit the development of a preventative intervention strategy that can be implemented appropriately and efficiently.