Epigenomic Predictors of PTSD and Traumatic Stress in an African American Cohort

项目摘要 创伤后应激障碍（PTSD）是一种与压力有关的精神障碍， 非裔美国人（AAs）我们早期的工作确定了关键的社会逆境因素，包括孤独， 歧视、累积的创伤、情感虐待和经济困难， 糖皮质激素受体调控网络基因的DNA甲基化， 症状严重程度。虽然研究白色和AA人群中PTSD的风险表明， AAs在创伤暴露后患PTSD的风险更高，很少有研究专门针对 研究了导致AA人群中不同风险的社会环境因素。人口内 研究有可能揭示最终导致PTSD风险种族/民族差异的暴露。 事实上，结构、心理和环境机制，如生活在不安全的环境中， 暴露于歧视，可能会导致不同的创伤后应激障碍的风险在AA。我们之前的研究证实了这些 调查结果。然而，尚不清楚的是：（i）积极的社会接触的潜在缓冲作用， 例如社会支持和凝聚力，这已被证明在减轻创伤后应激障碍风险方面发挥重要作用; 以及（ii）外周表观遗传测量与PTSD的靶器官-脑相关的程度。 外周表观基因组变异与中枢神经系统表观基因组学研究进展 为了获得更深入的机制，迫切需要脑相关表观基因组变异（本文称为脑相关表观基因组变异）。 深入了解受这种心理健康状况影响的AA之间与PTSD相关的健康差异。因此 这个更新应用程序的总体目标是提供对社会背景（积极的和 消极的，影响大脑相关的表观基因组变异，以影响创伤后应激障碍和创伤应激的风险， 以社区为基础的AA队列。为了实现这一目标，我们将利用公开可用的多组织数据集， 确定在大脑和血液中高度相关的表观基因组标记，并将我们提出的分析集中在 这些相关的措施使用现有的和新收集的表观基因组和基因表达数据， 底特律邻里健康研究（DNHS）队列。基因组数据将与DNHS调查数据配对， 其中包括社会逆境，精神病理学，社会支持和凝聚力的年度措施。我们将 重点分析我们早期工作中涉及的社会逆境（孤独，感知 歧视、累积创伤、经济困难、情感虐待）和积极的社会接触 PTSD（社会支持和邻里社会凝聚力）。这项研究的结果将 提供了一个更深层次的特征，社会暴露，无论是积极的还是消极的，如何影响大脑相关的 表观基因组过程影响AA中与压力相关的精神病理学，这是一个研究不足的美国少数民族 在创伤压力相关的精神病理学方面存在实质性健康差异的群体。

PROJECT SUMMARY Post-traumatic stress disorder (PTSD) is a debilitating stress-related mental disorder that disproportionately impacts African Americans (AAs). Our earlier work identified key social adversity factors, including loneliness, perceived discrimination, cumulative trauma, emotional maltreatment and financial difficulties that, in combination with DNA methylation in glucocorticoid receptor regulatory network genes, prospectively predicted PTSD symptom severity. While studies examining the risk of PTSD among white and AA populations have shown that AAs are at a higher risk of PTSD following traumatic exposure, there are few studies that have specifically examined the socioenvironmental factors that lead to differential risk within AA populations. Within-population studies have the potential to uncover exposures that ultimately lead to race/ethnic disparities in PTSD risk. Indeed, structural, psychosocial and environmental mechanisms, such as living in unsafe environments and exposure to discrimination, may contribute to differential PTSD risk in AAs. Our prior research confirms these findings. What remains unknown, however, are: (i) the potential buffering effects of positive social exposures, such as social support and cohesion, which have been shown to play an important role in mitigating risk of PTSD; and (ii) the extent to which peripheral epigenetic measures are relevant to the target organ of PTSD—the brain. Advances in the science of linking peripheral epigenomic variation to central nervous system (CNS) epigenomic variation (herein called brain-related epigenomic variation) is urgently needed in order to gain deeper mechanistic insight into PTSD-related health disparities among AAs affected by this mental health condition. Therefore, the overall goal of this renewal application is to provide mechanistic insight into how social context, both positive and negative, affects brain-related epigenomic variation to impact risk of PTSD and traumatic stress in a prospective, community-based cohort of AAs. To achieve this goal, we will leverage publicly available, multi-tissue datasets to identify epigenomic markers that are highly correlated in brain and blood, and focus our proposed analyses on these correlated measures using existing and newly collected epigenomic and gene expression data from the Detroit Neighborhood Health Study (DNHS) cohort. The genomic data will be paired with DNHS survey data, which includes annual measures of social adversity, psychopathology, and social support and cohesion. We will focus analyses on social adversities previously implicated in our earlier work (loneliness, perceived discrimination, cumulative trauma, financial difficulties, emotional mistreatment) and positive social exposures previously implicated in PTSD (social support and neighborhood social cohesion). Results from this study will provide a deeper characterization of how social exposures, both positive and negative, influence brain-related epigenomic processes to impact stress-related psychopathology among AAs, an under-studied U.S. minority group with substantial health disparities in traumatic-stress related psychopathology.