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）：雌性在创伤后发生创伤后应激障碍（PTSD）和/或严重的PTSD症状（PTS）的可能性是男性的两倍。有证据表明，这种差异可能在某种程度上具有生物学基础：通过获得的表观遗传改变可以在生物学上嵌入创伤，从而影响压力反应甚至对轻度的未来压力源。因此，PTSD/PT中的性别差异可能部分通过获得的表观遗传修饰来介导。计划中的研究线的长期目标是为减少与PTSD相关的性别/性别不平等的战略做出贡献。拟议的多学科试点研究的直接目的是收集设计全面R01的信息，以研究可能是PTSD/PTS中观察到的性别/性别差异的因素。 计划的R21研究将利用正在进行的R01调查的基础设施和资源来获取有关PTSD/PTS尤其高风险的亚组的表观遗传信息，即严重身体伤害的拉丁裔幸存者。 在R01研究设计的基础上，该设计将需要在住院后的几天内进行身体伤害幸存者的访谈，并在5个月的随访中，计划中的试点研究将在两次访谈中从100个子样本（即50名男性/50名女性）的子样本中收集血液样本。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可能幅度的初步信息，并确定涉及压力调节和脆弱性的几个不同基因中的哪些是对PTSD中性别/性别差异的进一步研究。 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）确定在最初受伤后评估中PACAP，NR3C1，RORA和ESR1的甲基化的程度可以解释性别与PTSD/PTS之间的联系。 （3）在5个月的随访中，是否可以检测到PACAP，NR3C1，RORA和ESR1的甲基化后创伤后的变化，以及任何变化的大小与性别或PTSD/PTS有关。 从拟议的研究中获得的知识有可能加速旨在减少PTSD相关的性别/性别差异的努力。具体而言，只要表观遗传过程是可修改的，这项研究可以为预防或治疗男性和女性的PTSD/PTSS奠定基础。这项研究还可能导致鉴定出具有PTSD脆弱性的新型生物标志物，并洞悉这些标记是否特定于性别。