Biomarkers of Posttraumatic Stress Disorder and Resilience in Women Veterans

描述(申请人提供)：大量女性退伍军人由于在服役期间暴露于与人际关系、战斗或战斗支持相关的创伤事件而患上创伤后应激障碍(PTSD)。然而，大多数女退伍军人不会经历任何重大的心理健康问题，尽管暴露在潜在的创伤事件中。在这两个不同的轨迹中，区分女性的因素还没有被很好地理解。本提案旨在通过使用神经成像和基因分型来确定女性退伍军人中创伤后应激障碍和复原力的客观生物标记物，从而开始解决这一问题。为此，患有和不患有创伤后应激障碍的女性退伍军人将被要求完成诊断性面谈，接受脑磁图(MEG)扫描，并提供血液样本进行基因分析。脑磁图是一种简单、简洁、非侵入性的神经成像工具，通过评估同步神经相互作用(SNI)，可以对各种情况进行稳健和准确的分类。先前的研究已经确定了精神分裂症、酒精依赖、阿尔茨海默病、干燥综合征、多发性硬化症和男性退伍军人的创伤后应激障碍等的MEG-SNI生物标记物。本提案将寻求将后一项研究结果推广到女性，以便(1)验证先前确定的创伤后应激障碍SNI生物标记物，或建立专用于女性的SNI生物标记物，以及(2)评估与不同创伤类型(例如，战斗与性侵犯)有关的退伍军人神经差异。此外，还将分析血液，以确定患有和不患有创伤后应激障碍的退伍军人女性的载脂蛋白E(ApoE)基因。长期以来，人们一直认为，暴露在创伤事件中的遗传影响对心理结果的重要性，是理解为什么一些人在面对创伤时具有韧性，而另一些人则会患上创伤后应激障碍或相关的心理健康问题。大多数这样的研究只关注少数几个基因，而且发现并不一致。载脂蛋白E在创伤后应激障碍的研究中一直被忽视，它参与了包括神经发育、再生和可塑性在内的许多功能，并与多种神经精神障碍有关。只有一项已发表的研究考察了载脂蛋白E和创伤后应激障碍之间的联系。这项建议中包括的初步研究进一步支持了男性退伍军人中载脂蛋白E与创伤后应激障碍之间的联系，并表明载脂蛋白E的某些特征可能会减轻创伤后应激障碍症状的严重程度。此外，这种影响似乎是通过对神经同步性的影响来解释的。这项建议将寻求扩展这一文献，并澄清载脂蛋白E、创伤后应激障碍和女性退伍军人神经功能之间的联系。这项研究的结果将提高对创伤后应激障碍和复原力的病理生理学的认识。最重要的是，确定创伤后应激障碍的客观指标将通过改善诊断并提供一个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，从而最终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.