Ecologic Stressors, PTSD, and Drug Use in Detroit

描述（由申请人提供）：本申请的总体目标是研究创伤后应激障碍（PTSD）病因学中特定遗传变异与社会环境之间的相互作用。我们提出这项工作是为了直接响应PAR 08-065“NIH关于研究健康中社会、行为和遗传因素之间相互作用的修订奖（R01）”。提出的工作将利用一个独特的机会，在底特律社区健康研究（DNHS）的成员中，为正在进行的创伤后应激障碍（PTSD）的多层次纵向研究增加遗传成分，这是一个具有代表性的基于人口的样本，包括1500名底特律城市居民（DA22720; PI: Sandro Galea）。据我们所知，目前还没有研究评估社会环境的特征如何改变PTSD的遗传影响。DNHS提供了个人和社区水平环境暴露的综合评估，因此是基因-环境相互作用多层次研究的独特资源。此外，DNHS已经获得资金从参与者身上收集血液样本。目前提案的资金将使我们能够提取DNA和基因型血液收集在这项研究中，并提供工资覆盖分子和统计遗传学专家。本补充研究的目的是：(1)评估与PTSD神经生物学相关的遗传变异（如SLC6A4， FKBP5）是否改变了底特律居民潜在创伤性事件与PTSD风险之间的纵向关系；(2)评估与PTSD神经生物学相关的遗传变异（如SLC6A4， FKBP5）是否改变了社会环境特征之间的纵向关系。经济劣势)和底特律居民患创伤后应激障碍的风险。公共卫生相关性：这是根据PAR 08-065“研究健康中社会、行为和遗传因素之间相互作用的NIH修订奖（R01）”提交的修订奖。我们的修订申请的总体目标是研究药物滥用和创伤后应激障碍（PTSD）病因学中特定遗传变异与社会环境特征之间的相互作用。拟议的修订奖将基因分型添加到已经资助的工作（DA022720）中，以最小的成本进行迄今为止创伤后应激障碍中基因-环境相互作用的第一个多层次研究。对PTSD中度易感性的基因变异的识别将为该疾病的病理生理学提供线索。反过来，这应该有助于寻找新的更有效的治疗和预防创伤后应激障碍的药物。了解可能形成创伤后应激障碍易感性的因素对于开发有效的干预措施以减轻创伤后应激障碍的后果至关重要。此外，这项研究涉及到一种独特的合作，其中包括从社会生态学角度开展这项工作的流行病学家、具有精神神经免疫学专业知识的流行病学家以及具有精神流行病学、分子和统计遗传学专业知识的合作者。因此，尽管本研究特别关注PTSD作为其感兴趣的关键分类结果，但这项工作的见解可能有助于指导我们理解生态压力源如何影响一系列健康结果，包括药物滥用/依赖。

DESCRIPTION (provided by applicant): The overall goal of this application is to investigate the interactions between specific genetic variants and the social environment, in the etiology of posttraumatic stress disorder (PTSD). We propose this work in direct response to PAR 08-065 "NIH Revision Awards for Studying Interactions Among Social, Behavioral, and Genetic Factors in Health (R01)". The proposed work will take advantage of a unique opportunity to add a genetic component to an ongoing multi-level longitudinal study of posttraumatic stress disorder (PTSD) in members of the Detroit Neighborhood Health Study (DNHS), a representative population-based sample of 1500 urban residents of Detroit (DA22720; PI: Sandro Galea). No existing work, as far as we are aware, has assessed how features of the social environment modify genetic influences on PTSD. The DNHS offers a comprehensive assessment of both individual and community-level environmental exposures and is, therefore, a unique resource for a multi-level study of gene- environment interaction. Moreover, the DNHS is already funded to collect blood samples from participants. Funding for the current proposal would enable us to extract DNA and genotype bloods collected in this study as well as provide salary coverage for molecular and statistical genetics expertise. The aims of this proposed supplemental study are (1) To assess whether genetic variants implicated in the neurobiology of PTSD (e.g., SLC6A4, FKBP5), modify the longitudinal relation between potentially traumatic events and risk of PTSD in residents of Detroit, and (2) To assess whether genetic variants implicated in the neurobiology of PTSD (e.g., SLC6A4, FKBP5), modify the longitudinal relation between features of the social environment (e.g., economic disadvantage) and the risk of PTSD in residents of Detroit. PUBLIC HEALTH RELEVANCE: This is a revision award submitted in response to PAR 08-065 "NIH Revision Awards for Studying Interactions Among Social, Behavioral, and Genetic Factors in Health (R01)". The overall goal of our revision application is to investigate the interactions between specific genetic variants and features of the social environment in the etiology of substance abuse and posttraumatic stress disorder (PTSD). The proposed Revision Award adds genotyping to already funded work (DA022720) to conduct the first multi- level study of gene-environment interaction in PTSD to date at minimal cost. The identification of genetic variants that moderate susceptibility to PTSD will provide clues to the pathophysiology of the disorder. That, in turn should facilitate the search for newer more effective pharmacological agents for PTSD treatment and prevention. Understanding factors that may shape vulnerability to PTSD is critically important for the development of effective interventions that can mitigate the consequences of PTSD. In addition, this study involves a unique collaboration between epidemiologists who bring to this work a social ecologic perspective, epidemiologists with expertise in psychoneuroimmunology and collaborators with expertise in psychiatric epidemiology, molecular and statistical genetics. Therefore, although this study is specifically focused on PTSD as its key categorical outcomes of interest, insights from this work may help guide our understanding of how ecologic stressors influence a range of heath outcomes, including drug abuse/dependence.