Genes, Environment, Family and Mental Health

 描述(申请人提供)：精神障碍是全球残疾的主要来源。除了造成个人痛苦外，与这些障碍相关的残疾还包括对家庭和健康结果的重大后果。剖析家庭、社区和精神因素之间的关系是复杂的，因为它们之间存在很高的互为因果的可能性。这一结果对理解精神障碍在一系列不良后果中的作用是一个艰巨的挑战。理清这种复杂关系的第一步是确定在精神障碍形成之前的因果因素的作用，以便后续步骤可以估计精神障碍在长期结果中的中介力量，如家庭变化和变异。在这里，我们建议迈出这第一步，使用一种变革性的新方法，有可能显着推进心理健康和家庭的研究。这个项目将利用一系列前所未有的机会来促进我们对精神障碍形成的理解。我们建议整合：(1)具有特殊社会环境测量的长期社区和家庭小组研究(Chitwan Valley Family Study-CVFS)；(2)风险因素暴露异常高的环境(南亚)；以及(3)精神病学遗传学的最新进展，已确定导致精神障碍的多基因风险特征。我们专注于三种常见的、与家庭和社会环境关系最好的精神病学表型：重度抑郁障碍(MDD)、创伤后应激障碍(PTSD)和酒精使用障碍(AUD)。我们的具体目标是：(目标1)通过收集CVFS参与者的精神表型、人口统计信息和生物标本，创建独特的科学资源。这项研究是由新西兰排雷中心资助的一项现有研究，包括来自不同次级人口群体的2 600个家庭的9 499人；(目的2)进行人口统计学/流行病学分析，以对照对照设计，在南亚家庭和社区的大量人口样本中确定精神疾病的关键预测因素；(目的3)进行全基因组基因分型，并进行分析，以检查环境风险和复原力因素的多基因风险分数和遗传修饰物的作用。这些目标的成功完成将：(1)首次将散居海外的欧洲人的精神健康和精神遗传学的人口学/流行病学研究结果推广到南亚人口；(2)确定社区变化和基因-环境相互作用在产生最有可能影响长期家庭结果的常见精神疾病方面的作用；(3)为科学界创造一种变革性的新资源，以利用我们对精神疾病的理解方面的进展，了解这些疾病可能塑造许多不同的晚年个人、家庭和健康结果的潜力。

 DESCRIPTION (provided by applicant): Psychiatric disorders are the leading source of disability worldwide. In addition to the individual suffering they entail, the disability associate with these disorders includes substantial consequences for family and health outcomes. Dissecting the relationship among family, community and psychiatric factors is complex because of the high potential for reciprocal causation among them. The result is a formidable challenge to understanding the role of psychiatric disorders in a wide range of adverse outcomes. The first step toward disentangling this complex relationship is to identify the role of causal factors that precede the formation of psychiatric disorders so that subsequent steps can estimate the mediating power of psychiatric disorders in long-term outcomes, such as family change and variation. Here we propose to take this first step using a transformative new approach with the potential to significantly advance the study of both mental health and family. This project will capitalize on a confluence of unprecedented opportunities to advance our understanding of the formation of psychiatric disorders. We propose to integrate: (1) a long-term community and family panel study with exceptional measurement of social environment (the Chitwan Valley Family Study - CVFS); (2) a setting of unusually high exposures to risk factors (South Asia); and (3) recent advances in psychiatric genetics that have identified polygenic risk profiles contributing to psychiatric disorders. We focus on three psychiatric phenotypes that are common and have the best established relationship to family and social environment: major depressive disorder (MDD), post-traumatic stress disorder (PTSD), and alcohol use disorders (AUD). Our specific aims are: (Aim 1) Create a unique scientific resource by collecting psychiatric phenotypes, demographic information and biospecimens from participants in the CVFS. The CVFS is an existing NICHD- funded study comprising 9,499 individuals from 2,600 households in various sub-population groups; (Aim 2) Conduct demographic/epidemiologic analyses to identify key predictors of psychiatric disorder in a large population-based sample of South Asian families and communities in a controlled-comparison design; (Aim 3) Perform genome wide genotyping and conduct analyses to examine the role of polygenic risk scores and genetic modifiers of environmental risk and resilience factors. The successful completion of these aims will: (1) For the first time, extend both the demography/epidemiology of mental health and psychiatric genetic findings from the European Diaspora to South Asian populations; (2) Establish the role of community change and gene- environment interactions in producing common psychiatric disorders most likely to shape long-term family outcomes; and (3) Create a transformative new resource for the scientific community to harness advances in our understanding of psychiatric disorders to learn the potential of those disorders to shape many different later life personal, family and health outcomes.