Biomarkers for Marine PTSD Risk and Resilience

描述（由申请人提供）：为什么一些暴露于创伤性事件的人会发展为创伤后应激障碍（PTSD），而另一些人则不会？风险和恢复力是理解PTSD病因学的两个重要概念。过去对创伤后应激障碍的研究已经确定了不同的因素，如家族史、童年经历、性格变量和先前存在的精神障碍，这些因素可能使个体患创伤后应激障碍的风险更高。复原力的概念，通常被认为是对创伤性事件负面影响的抵抗，在PTSD的任何考虑中也是非常重要的。弹性可以定义为“成功适应压力源的能力，在逆境中保持心理健康。”然而，同样重要的是复原力的概念，即PTSD发展后的复原能力。与PTSD风险相关的生物学因素，以及复原力的两个方面，目前还知之甚少。该项目将利用基因组方法和一系列行为和生物学评估，在海军陆战队员暴露于战斗压力前后，调查与创伤后应激障碍发展相关的生物风险和恢复力因素。具体来说，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。最初的创伤暴露后PTSD的发展变化很大，有些人从未表现出PTSD的迹象，而另一些人尽管经过多年的综合治疗，仍被丧失行为能力的症状所困扰。目前，心理弹性的基本特征尚不清楚，目前还无法预测这种疾病的发展，更不用说预测任何特定个体的最终结果了。如果能够发现与风险相关的生物标志物，它们可能有助于确定哪些个体处于风险之中，并制定更有效的一级预防方案。虽然环境因素对PTSD的发展显然是必不可少的，但这种疾病也有明显的遗传成分。我们计划在本研究中确定基于基因的PTSD生物标志物，以更好地了解与PTSD发生风险相关的生物学因素；以及以抵抗PTSD发展为代表的复原力。为了实现这些目标，我们提出了以下两个具体目标：具体目标1：确定外周血单核细胞中创伤后应激障碍风险和恢复力的基于基因表达的生物标志物谱；具体目标2：确定外周血单核细胞风险和恢复力的基于基因表达的生物标志物谱的变化。公共卫生相关性：创伤后应激障碍（PTSD）的发展在最初的创伤暴露后是非常可变的。虽然有些人从未表现出创伤后应激障碍的迹象，但其他人尽管经过多年的综合治疗，仍被丧失行为能力的症状所困扰。了解经历过创伤后应激障碍的战斗暴露个体的基因表达模式，将其与没有经历过创伤后应激障碍的战斗暴露个体的基因表达模式进行比较，将揭示与创伤后应激障碍有关的生物学机制，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.