Sex Gender Differences in Post Traumatic Stress Disorder

创伤后应激障碍的性别差异

• 批准号: 8682833
• 负责人: GRANT MARSHALL
• 金额: $ 20.38万
• 依托单位: RAND CORPORATION
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-01 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8682833
• 关键词: Accounting; Adult; Affect; Biological; Biological Markers; Biosensor; Blood; Blood specimen; Clinical; Clinical Research; Collaborations; Data; Development; ESR1 gene; Early identification; Ensure; Epigenetic Process; Event; Exposure to; Female; Foundations; Funding; Future; Gender; Genes; Genetic; Goals; Grant; Hospitalization; Human; Injury; Interdisciplinary Study; Intervention; Interview; Investigation; Knowledge; Latino; Link; Mediating; Methylation; Modification; Moods; NR3C1 gene; National Institute of Dental and Craniofacial Research; Participant; Persons; Physical Examination; Pilot Projects; Post-Traumatic Stress Disorders; Prospective Studies; RORA gene; Recording of previous events; Recruitment Activity; Regulation; Research; Research Activity; Research Design; Research Infrastructure; Resources; Risk; Role; Salivary; Sampling; Severities; Sex Characteristics; Staging; Stress; Subgroup; Survivors; Symptoms; Testing; Time; Trauma; Woman; Work; base; cost; design; disorder risk; follow-up; high risk; injured; insight; male; men; multidisciplinary; novel; novel strategies; peripheral blood; pituitary adenylate cyclase activating polypeptide; point of care; preclinical study; prevent; programs; public health relevance; sex; stressor; tool

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.

描述（由申请人提供）：女性在遭受创伤后出现创伤后应激障碍 (PTSD) 和/或严重 PTSD 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而在生物学上嵌入，这些改变会影响对未来轻微压力源的应激反应。因此，PTSD/PTS 的性别差异可能部分是由获得性表观遗传修饰介导的。计划研究的长期目标是促进制定战略，减少与创伤后应激障碍相关的性/性别不平等。拟议的多学科试点研究的直接目标是收集设计全面 R01 调查所需的信息，调查可能导致 PTSD/PTS 中观察到的性别差异的因素。 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，以获得 PTSD/PTS 风险特别高的亚组（即遭受严重身体伤害的拉丁裔幸存者）的表观遗传信息。 R01 研究设计需要在住院几天内和 5 个月的随访中对身体伤害幸存者进行访谈，计划的试点研究将从 100 名子样本（即 50 名男性/50 名女性）中收集血液样本在两次采访中。血液数据将与访谈数据联系起来，以收集有关关键表观遗传效应的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的哪一个最有希望进一步进行 PTSD 性别/性别差异的 R01 研究。 计划中的R21有以下具体目标：（1）探讨四个压力和情绪相关基因（PACAP、NR3C1、RORA、ESR1）位点甲基化与终生创伤史之间的横截面关联的大小和方向（拉丁裔男性和女性的事件数量、事件严重性、类型和长期性）和基线 PTS。 (2) 在考虑终生创伤暴露后，确定初始损伤后评估时 PACAP、NR3C1、RORA 和 ESR1 的甲基化程度可以解释性别与随后的 PTSD/PTS 之间的联系。 (3) 评估创伤后PACAP、NR3C1、RORA和ESR1甲基化变化是否可以在5个月的随访中检测到，以及任何变化的幅度是否与性别或PTSD/PTS有关。 从拟议研究中获得的知识有可能加速旨在减少与创伤后应激障碍相关的性别差异的努力。具体来说，只要表观遗传过程是可修改的，这一系列研究就可以为预防或治疗男性和女性的 PTSD/PTSS 的定制干预措施奠定基础。这项研究还可能导致鉴定出易受创伤后应激障碍（PTSD）影响的新型生物标志物，并深入了解这些标志物是否具有性别特异性。