Genes, Environment, Family and Mental Health

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 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.