Biomarkers for Marine PTSD Risk and Resilience

描述(申请人提供)：为什么一些暴露在创伤性事件中的人会患上创伤后应激障碍(PTSD)，而另一些人则不会？风险和韧性是理解创伤后应激障碍病因的两个重要概念。过去关于创伤后应激障碍的研究发现，不同的因素可能会使个人患上创伤后应激障碍的风险更大，如家族史、童年经历、人格变量和先前存在的精神障碍。复原力的概念通常被认为是对创伤性事件的负面影响的抵抗，在任何关于创伤后应激障碍的考虑中也是非常重要的。韧性可以被定义为“成功地适应压力源，在面对逆境时保持心理健康的能力。”然而，同样重要的是复原力的概念，即在创伤后应激障碍发展后改善的能力。与患创伤后应激障碍风险相关的生物学因素以及复原力的两个方面都知之甚少。该项目将利用基因组方法和一系列行为和生物评估方法，在海军陆战队暴露于战斗压力前后的样本中调查与创伤后应激障碍发展相关的生物风险和复原力因素。具体地说，我们建议研究基于基因表达的创伤后应激障碍风险和恢复力的生物标志物。在最初的创伤暴露后，创伤后应激障碍的发展是相当不同的，一些人从未表现出创伤后应激障碍的迹象，而另一些人尽管进行了多年的联合治疗，但仍被丧失能力的症状所困扰。目前，复原力的基本特征尚不清楚，目前还不可能预测疾病的发展，更不用说任何特定个人的最终结果了。如果能够发现与风险相关的生物标记物，它们可能有助于识别哪些人处于风险之中，并导致更有效的初级预防方案。虽然环境因素显然对创伤后应激障碍的发展至关重要，但这种疾病也有明显的遗传因素。在这项研究中，我们计划识别基于基因的创伤后应激障碍的生物标志物，以更好地了解与创伤后应激障碍的发生风险以及与创伤后应激障碍的抵抗相关的生物学因素。为了实现这些目标，我们提出了两个具体目标：具体目标1：确定外周血单核细胞创伤后应激障碍风险和弹性的基于基因表达的生物标记物谱；具体目标2：确定外周血单核细胞基于基因表达的风险和恢复力生物标志物谱的变化。公共卫生相关性：在最初的创伤暴露后，创伤后应激障碍(PTSD)的发展是极不稳定的。虽然有些人从来没有表现出创伤后应激障碍的迹象，但另一些人尽管进行了多年的联合治疗，但仍被丧失能力的症状所困扰。了解经历创伤后应激障碍的战斗暴露者的基因表达模式，与没有经历创伤后应激障碍的战斗暴露者的基因表达模式相比，将有助于阐明创伤后应激障碍涉及的生物学机制，并为更有效地预防和治疗这种毁灭性疾病提供基础。

DESCRIPTION (provided by applicant): Why do some individuals exposed to traumatic events develop Post-traumatic Stress Disorder (PTSD), while others do not? Risk and resilience are two concepts that are important in understanding the etiology of PTSD. Past research on PTSD has identified different factors that may put individuals at greater risk of developing PTSD, such as family history, childhood experiences, personality variables, and preexisting mental disorders. The concept of resilience, often considered to represent resistance to the negative effects of a traumatic event, is also very important in any consideration of PTSD. Resilience can be defined as "the ability to successfully adapt to stressors, maintaining psychological well-being in the face of adversity." Equally as important, however, is the concept of resilience as the ability to improve after the development of PTSD. The biological factors associated with the risk of developing PTSD, as well as both aspects of resilience are poorly understood. This project will investigate biological risk and resilience factors associated with the development of PTSD among a sample of Marines before and after they are exposed to combat stress utilizing genomic methodologies and a battery of behavioral and biological assessments. Specifically, we propose to investigate gene- expression based biomarkers of PTSD risk and resilience. The development of PTSD following initial traumatic exposure is quite variable, with some individuals never exhibiting signs of PTSD, while others are plagued with incapacitating symptoms despite years of combinations of therapy. At present, the basic characteristics underlying resilience are unknown, and it is not currently possible to predict the development of the disorder, much less any eventual outcome in any given individual. If biomarkers related to risk can be discovered, they may help to identify which individuals are at risk, and lead to more effective primary prevention protocols. Although environmental factors are clearly essential for the development of PTSD, the disorder also has a demonstrable genetic component. We plan in this study to identify gene-based biomarkers of PTSD in an effort to better understand the biological factors related to both the risk of developing PTSD; and to resilience as represented by resistance to development of PTSD. To accomplish these objectives, we have proposed two specific aims as follows: Specific Aim 1: Identify gene-expression-based biomarker profiles of PTSD risk and resilience in peripheral blood mononuclear cells and Specific Aim 2: Identify changes in gene-expression-based biomarker profiles of risk and resilience in peripheral blood mononuclear cells. PUBLIC HEALTH RELEVANCE: The development of Post Traumatic Stress Disorder (PTSD) following initial traumatic exposure is extremely variable. While some individuals never exhibit signs of PTSD, others are plagued with incapacitating symptoms despite years of combinations of therapy. Understanding the gene expression patterns of combat-exposed individuals who go one to experience PTSD, as compared to the gene expression patterns of combat-exposed individuals who did not go on to experience PTSD, will shed light on the biological mechanisms involved in PTSD and provide a basis for more effective prevention and treatment of this devastating disorder.