Candidate Epigenetic Biomarkers For PTSD: Insights From Detroit

PTSD 候选表观遗传生物标志物：来自底特律的见解

• 批准号: 7811044
• 负责人: Allison E Aiello
• 金额: $ 49.73万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7811044
• 关键词: Address; Affect; Area; Biological; Biological Markers; Candidate Disease Gene; Chronic; Cohort Studies; Complex; DNA; DSM-IV; Data; Diagnostic; Disadvantaged; Disease; Economics; Epidemiology; Epigenetic Process; Etiology; Gene Expression; Genes; Genome; Goals; Health; Individual; Injury; Intervention; Interview; Life; Link; Longitudinal Studies; Mental disorders; Methylation; Modification; Molecular; Molecular Profiling; Nature; Neighborhoods; Peripheral Blood Mononuclear Cell; Persons; Pharmaceutical Preparations; Population; Post-Traumatic Stress Disorders; Predisposition; Psychopathology; Public Health; RNA; Research Activity; Research Proposals; Risk; Sampling; Source; Specimen; Structure; Surveys; Testing; Trauma; United States; Validation; Variant; Work; base; candidate identification; cohort; cost; experience; genome-wide; insight; meetings; prevent; promoter; psychologic; socioeconomics; stressor; true biomarker

DESCRIPTION (provided by applicant): This application addresses broad Challenge Area (03) Biomarker Discovery and Validation and specific Challenge Topic 03-MH-101 Biomarkers in mental disorders. Post-traumatic stress disorder (PTSD) is one of the more common and disabling mental illnesses in the US. Recent work has identified distinct gene expression profiles among persons meeting DSM-IV diagnostic criteria for PTSD compared to trauma-exposed persons who did not develop PTSD. Molecular psychiatric studies based upon both candidate gene and whole genome approaches suggest that specific epigenetic profiles are associated with mental illness. Such profiles may plausibly induce the gene expression difference observed in PTSD-affected vs. -unaffected individuals; however, the contribution of epigenetic changes in the etiology of this disorder is currently unknown. We therefore hypothesize that PTSD is accompanied by epigenetic modification of loci whose activity contributes to the disorder. The proposed project will take advantage of a unique opportunity to test this hypothesis using samples obtained from an ongoing, multi-level longitudinal study of Detroit residents, the Detroit Neighborhood Health Study (DNHS). The present study specifically seeks to: (1) Assess whether methylation profiles differ among individuals with current PTSD, those who have once had PTSD but are now PTSD free, and individuals who have been trauma exposed but never developed the disorder, and (2) Assess whether gene expression profiles differ among individuals with current PTSD, those who have once had PTSD but are now PTSD free, and individuals who have been trauma exposed but never developed the disorder. In addition, for individuals presenting with newly developed cases of PTSD, we will test not only the samples collected during wave two of the study, but also the banked, "pre-PTSD" samples from these same individuals obtained during wave one. Thus, the proposed research activity will conduct the first multi-level study of the epigenetic signatures associated with PTSD to date at minimal cost. Identification of such epigenetic variants will facilitate the search for new and/or more effective pharmacological and psychological interventions to prevent or treat the disorder, and will advance our understanding of the etiology of complex mental illnesses such as PTSD. Finally, given the financial difficulties that Detroit residents have experienced over the past several years, the proposed work includes an unprecedented opportunity to uncover how socioeconomic disadvantage may modify the epigenetic signatures observed among individuals affected by PTSD and, most importantly, to employ residents of Detroit-one of the areas worst affected by the current economic downturn-as part of the project. The proposed study will assess methylation and gene expression profiles among PTSD-affected and - unaffected individuals, all of whom are residents of Detroit. The findings from this study will have important public health implications, including identification of candidate epigenetic biomarkers associated with PTSD that may predict the risk for and course of this disorder.

描述（由申请人提供）：本申请涉及广泛的挑战领域（03）生物标志物发现和验证以及特定的挑战主题03-MH-101精神障碍生物标志物。创伤后应激障碍（PTSD）是美国最常见的精神疾病之一。最近的工作已经确定了不同的基因表达谱之间的人符合DSM-IV诊断标准的PTSD相比，创伤暴露的人谁没有发展PTSD。基于候选基因和全基因组方法的分子精神病学研究表明，特定的表观遗传特征与精神疾病相关。这些特征可能会诱导PTSD受影响与未受影响个体中观察到的基因表达差异;然而，表观遗传变化在这种疾病病因学中的作用目前尚不清楚。因此，我们假设PTSD伴随着基因座的表观遗传修饰，这些基因座的活性导致了这种疾病。拟议的项目将利用一个独特的机会来测试这一假设，使用从底特律居民正在进行的多层次纵向研究中获得的样本，底特律社区健康研究（DNHS）。本研究具体旨在：（1）评估甲基化谱在患有当前PTSD的个体、曾经患有PTSD但现在没有PTSD的个体、以及已经暴露于创伤但从未发展出该病症的个体之间是否不同，以及（2）评估基因表达谱在患有当前PTSD的个体、曾经患有PTSD但现在没有PTSD的个体之间是否不同，以及那些受过创伤但从未患上这种疾病的人。此外，对于出现新的PTSD病例的个体，我们不仅将测试在研究的第二波期间收集的样本，而且还将测试在第一波期间从这些相同个体获得的“PTSD前”样本。因此，拟议的研究活动将以最低的成本进行迄今为止与PTSD相关的表观遗传特征的第一次多层次研究。鉴定这种表观遗传变异将有助于寻找新的和/或更有效的药理学和心理干预措施来预防或治疗这种疾病，并将促进我们对复杂精神疾病（如PTSD）病因的理解。最后，考虑到底特律居民在过去几年中经历的经济困难，拟议的工作包括一个前所未有的机会，以揭示社会经济劣势如何改变受创伤后应激障碍影响的个人中观察到的表观遗传特征，最重要的是，雇用底特律居民-受当前经济衰退影响最严重的地区之一-作为项目的一部分。这项拟议中的研究将评估PTSD受影响和未受影响的个体之间的甲基化和基因表达谱，所有这些人都是底特律居民。这项研究的结果将具有重要的公共卫生意义，包括鉴定与PTSD相关的候选表观遗传生物标志物，这些生物标志物可能预测这种疾病的风险和病程。