Sex Gender Differences in Post Traumatic Stress Disorder

描述（由申请人提供）：女性在创伤暴露后出现创伤后应激障碍（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，这种差异可能在一定程度上有生物学基础：创伤暴露可以通过后天的表观遗传改变在生物学上嵌入，这种改变会影响对未来甚至轻微的压力源的应激反应。因此，PTSD/PTS的性别差异可能部分由后天表观遗传修饰介导。该研究计划的长期目标是有助于制定减少与创伤后应激障碍相关的性别/性别不平等的策略。这项拟议的多学科试点研究的直接目的是收集所需的信息，以设计一项全面的R01调查，研究可能导致PTSD/PTS中观察到的性别/性别差异的因素。计划中的R21研究将利用正在进行的R01调查的基础设施和资源，获得PTSD/PTS特别高风险亚群的表观遗传信息，即严重身体伤害的拉丁裔幸存者。

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.