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)的病因学中特定基因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“美国国立卫生研究院修订奖，用于研究健康中社会、行为和遗传因素之间的相互作用(R01)”。拟议的工作将利用一个独特的机会，在底特律社区健康研究(DNHS)成员中正在进行的创伤后应激障碍(PTSD)多水平纵向研究中增加基因成分，底特律社区健康研究(DNHS)是底特律1500名城市居民的代表性人口样本(DA22720；PI：Sandro Galea)。就我们所知，目前还没有工作评估社会环境的特征如何改变基因对创伤后应激障碍的影响。DNHS提供了对个人和社区层面的环境暴露的全面评估，因此是基因与环境相互作用的多层次研究的独特资源。此外，DNHS已经获得了从参与者那里收集血液样本的资金。为目前的提案提供资金将使我们能够提取在这项研究中收集的DNA和基因型血，并为分子和统计遗传学专业知识提供工资覆盖。这项拟议补充研究的目的是(1)评估与创伤后应激障碍神经生物学有关的遗传变异(例如SLC6A4、FKBP5)是否改变了底特律居民潜在创伤事件与创伤后应激障碍风险之间的纵向关系；以及(2)评估与创伤后应激障碍神经生物学有关的基因变异(例如SLC6A4、FKBP5)是否改变了社会环境特征(例如，经济劣势)与底特律居民创伤后应激障碍风险之间的纵向关系。公共卫生相关性：这是为响应PAR 08-065《美国国立卫生研究院修订奖，研究健康中社会、行为和遗传因素之间的相互作用(R01)》而提交的修订奖。我们修订应用程序的总体目标是调查物质滥用和创伤后应激障碍(PTSD)的病因学中特定遗传变异和社会环境特征之间的相互作用。拟议的修订奖在已经获得资助的工作(DA022720)的基础上增加了基因分型，以最低的成本进行迄今为止第一个关于创伤后应激障碍基因与环境相互作用的多水平研究。鉴定对创伤后应激障碍具有中等易感性的遗传变异将为该疾病的病理生理学提供线索。这反过来应有助于寻找更新、更有效的药理制剂来治疗和预防创伤后应激障碍。了解可能影响创伤后应激障碍易感性的因素对于制定能够减轻创伤后应激障碍后果的有效干预措施至关重要。此外，这项研究涉及将社会生态观点带到这项工作的流行病学家、具有心理神经免疫学专业知识的流行病学家和具有精神病学流行病学、分子和统计遗传学专业知识的合作者之间的独特合作。因此，尽管这项研究特别关注创伤后应激障碍的关键分类结果，但这项工作的见解可能有助于指导我们理解生态应激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.