Biomarkers of Posttraumatic Stress Disorder and Resilience in Women Veterans

描述（由申请人提供）：由于在服役期间暴露于人际、战斗或战斗支持相关的创伤事件，大量女性退伍军人患上了创伤后应激障碍（PTSD）。然而，尽管暴露于潜在的创伤性事件，大多数女退伍军人不会经历任何重大的心理健康问题。在这两种截然不同的轨迹中区分妇女的因素还没有得到很好的理解。目前的建议旨在通过使用神经成像和基因分型识别女性退伍军人创伤后应激障碍和恢复力的客观生物标志物，开始解决这一问题。为此，患有或没有创伤后应激障碍的女退伍军人将被要求完成诊断性访谈，接受脑磁图扫描，并提供血液样本用于基因分析。MEG是一种简单、简短、无创的神经成像工具，通过评估同步神经相互作用（SNI），可以对各种疾病进行稳健、准确的分类。先前的研究已经确定了MEG-SNI生物标志物，用于男性退伍军人的精神分裂症、酒精依赖、阿尔茨海默病、干燥综合征、多发性硬化症和创伤后应激障碍等。目前的提案将寻求将后一项发现扩展到女性，以便(1)验证先前确定的创伤后应激障碍SNI生物标志物或建立特定于女性的SNI生物标志物；(2)评估女性退伍军人与不同创伤类型（例如，战斗与性侵犯）相关的神经差异。此外，将分析血液，以确定载脂蛋白E （apoE）基因型退伍妇女有和没有创伤后应激障碍。长期以来，基因对创伤性事件暴露后心理结果的影响一直被认为是理解为什么有些人在面对创伤时能恢复过来，而另一些人则会患上创伤后应激障碍或相关心理健康问题的核心。大多数这类研究只关注少数基因，结果也不一致。ApoE在创伤后应激障碍的研究中很大程度上被忽视了，它涉及许多功能，包括神经发育、再生和可塑性，并与几种神经精神疾病有关。只有一项已发表的研究调查了apoE和创伤后应激障碍之间的关系。本提案中包括的初步研究进一步支持apoE与男性退伍军人创伤后应激障碍之间的联系，并表明apoE的某些特征可能减轻创伤后应激障碍症状的严重程度。此外，这种效果似乎可以通过对神经同步的影响来解释。本提案将寻求扩展这些文献，并澄清apoE、PTSD和女性退伍军人神经功能之间的联系。本研究的结果将提高对创伤后应激障碍病理生理学和心理恢复能力的认识。最重要的是，确定创伤后应激障碍的客观指标将最终通过改进诊断和提供客观的基于生物学的指标来跟踪患有这种毁灭性疾病的人的治疗结果，从而改善退伍军人的健康和治疗。

DESCRIPTION (provided by applicant): A large number of women veterans have developed posttraumatic stress disorder (PTSD) as a result of exposure to interpersonal, combat, or combat-support related traumatic events during their time in the service. However, the majority of women veterans will not experience any significant mental health problems despite exposure to potentially traumatic events. Factors that distinguish women in these two distinct trajectories are not well-understood. The present proposal aims to begin to address this issue by identifying objective biomarkers of PTSD and resilience in women veterans using neuroimaging and genotyping. To that end, women veterans with and without PTSD will be asked to complete diagnostic interviews, undergo a magnetoencephalography (MEG) scan, and provide a blood sample for genetic analyses. MEG is a simple, brief, non-invasive neuroimaging tool that permits robust and accurate classification of various conditions by evaluating synchronous neural interactions (SNI). Prior research has identified MEG-SNI biomarkers for schizophrenia, alcohol dependence, Alzheimer's disease, Sjogren's syndrome, multiple sclerosis, and PTSD in male veterans, among others. The present proposal will seek to extend the latter findings to women in order to (1) validate the previously identified SNI biomarker of PTSD or establish an SNI biomarker specific to women and (2) evaluate neural differences associated with different trauma types (e.g., combat vs. sexual assault) in women veterans. In addition, blood will be analyzed to determine Apolipoprotein E (apoE) genotype of veteran women with and without PTSD. The importance of genetic influences on psychological outcomes following exposure to traumatic events has long been regarded as central to understanding why some people are resilient in the face of trauma and others develop PTSD or related mental health problems. Most such studies have focused on only a few genes and the findings have been inconsistent. ApoE, which has been largely overlooked in the study of PTSD, has been implicated in numerous functions including neural development, regeneration, and plasticity and has been associated with several neuropsychiatric disorders. Only one published study has examined the association between apoE and PTSD. Preliminary studies included in this proposal further support an association between apoE and PTSD in male veterans and suggest that certain characteristics of apoE may reduce the severity of PTSD symptoms. Furthermore, this effect appears to be accounted for by effects on neural synchrony. This proposal will seek to extend this literature and clarify the associations between apoE, PTSD, and neural functioning in women veterans. The results of this study will improve knowledge on the pathophysiology of PTSD and resilience. Most important, identification of an objective indicator of PTSD will ultimately enhance veterans' health and treatment by improving diagnoses and providing an objective biologically-based indicator to track treatment outcomes for those suffering from this devastating illness.