Sex Gender Differences in Post Traumatic Stress Disorder

描述（由申请人提供）：女性发生创伤后应激障碍（PTSD）和/或严重创伤后应激障碍症状（PTS）的可能性是男性的两倍。有证据表明，这种差异可能部分具有生物学基础：创伤暴露可以通过后天的表观遗传改变来生物学嵌入，这些表观遗传改变会影响对即使是轻微的未来压力源的压力反应。因此，PTSD/PTS的性别差异可能部分由后天表观遗传修饰介导。计划的研究路线的长期目标是促进战略的发展，以减少与创伤后应激障碍有关的性/性别不平等。拟议的多学科试点研究的直接目标是收集所需的信息，设计一个全面的R 01调查的因素，可能会观察到的PTSD/PTS的性别/性别差异。 计划中的R21研究将利用正在进行的R 01研究的基础设施和资源，以获得PTSD/PTS风险特别高的亚组的表观遗传信息，即，拉丁裔严重身体伤害的幸存者。 在R 01研究设计的基础上，该研究设计需要在住院的几天内和5个月的随访中与身体伤害幸存者进行访谈，计划的试点研究将从100个子样本中收集血液样本（即，50名男性/50名女性）。血液数据将与访谈数据相联系，以收集有关关键表观遗传效应可能程度的初步信息，并确定参与压力调节和脆弱性的几个不同基因中哪一个最有希望用于PTSD性别/性别差异的进一步R 01研究。 计划中的R21有以下具体目标：（1）在拉丁美洲男性和女性中探索四个压力和情绪相关基因（PACAP，NR 3C 1，RORA，ESR 1）位点甲基化与终身创伤史（事件数量，事件严重程度，类型和慢性）和基线PTS之间的横断面关联的大小和方向。(2)在解释终生创伤暴露后，确定在初始损伤后评估时PACAP、NR 3C 1、RORA和ESR 1甲基化的程度可以解释性别与随后的PTSD/PTS之间的联系。(3)评估是否可以在5个月随访时检测到PACAP、NR 3C 1、RORA和ESR 1甲基化的创伤后变化，以及任何变化的幅度是否与性别或PTSD/PTS相关。 从拟议的研究中获得的知识有可能加速旨在减少PTSD相关性/性别差异的努力。具体而言，只要表观遗传过程是可修改的，这一系列研究可以为预防或治疗男性和女性PTSD/PTSS的量身定制的干预措施奠定基础。这项研究也可能导致鉴定创伤后应激障碍脆弱性的新生物标志物，并深入了解这些标志物是否具有性别特异性。

DESCRIPTION (provided by applicant): Females are twice as likely as males to develop posttraumatic stress disorder (PTSD) and/or severe PTSD symptoms (PTS) following trauma exposure. Evidence suggests that this disparity may, in part, have a biological basis: trauma exposure can be biologically embedded via acquired epigenetic alterations that affect stress reactivity to even mild future stressors. Thus, sex differences in PTSD/PTS may be mediated, in part, by acquired epigenetic modifications. The long-term goal of the planned line of research is to contribute to the development of strategies to reduce sex/gender inequities associated with PTSD. The immediate objective of the proposed multidisciplinary pilot study is to collect information needed to design a full-scale R01 investigation of factors that might underlie observed sex/gender differences in PTSD/PTS. The planned R21 study would leverage the infrastructure and resources of an ongoing R01 investigation to obtain epigenetic information on a subgroup at especially high risk for PTSD/PTS, i.e., Latino survivors of serious physical injury. Building on the R01 study design, which would entail interviews with physical injury survivors within days of hospitalization and at 5-month follow-up, the planned pilot study would collect blood samples from a subsample of 100 (i.e., 50 males/50 females) at both interviews. Blood data will be linked with interview data to gather preliminary information about the likely magnitude of key epigenetic effects and to determine which of several different genes involved in stress regulation and vulnerability are most promising for further R01 study of sex/gender differences in PTSD. The planned R21 has the following specific aims: (1) To explore the magnitude and direction of cross-sectional associations between methylation at loci of four stress- and mood-related genes (PACAP, NR3C1, RORA, ESR1) and lifetime trauma history (number of events, event severity, type, and chronicity) and baseline PTS in Latino men and women. (2) To determine the degree to which methylation of PACAP, NR3C1, RORA, and ESR1 at the initial post-injury assessment can explain the link between sex and subsequent PTSD/PTS, after accounting for lifetime trauma exposure. (3) To appraise whether post-trauma changes in methylation of PACAP, NR3C1, RORA, and ESR1 can be detected at 5-month follow-up, and whether the magnitude of any change is related to sex or to PTSD/PTS. The knowledge obtained from the proposed research has the potential to accelerate efforts aimed at reducing PTSD-related sex/gender disparities. Specifically, insofar as epigenetic processes are modifiable, this line of research can lay the foundation for tailored interventions to prevent or treat PTSD/PTSS in men and women. This research may also result in identification of novel biomarkers of vulnerability to PTSD, and insights into whether these markers are sex-specific.