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William G. Axinn photo

Understanding the Connections among Genes, Environment, Family Processes, and Mental Health

a PSC Research Project

Investigators:   William G. Axinn, Dirgha J. Ghimire, Colter Mitchell

Psychiatric disorders are the leading source of disability worldwide. These disorders have profound impacts on individuals and families, including long-term consequences for family formation and dissolution. Dissecting the relationship among community, family, and psychiatric factors is complex because of the high potential for reciprocal causation, which creates a formidable challenge to analyzing the role of psychiatric disorders in a range of adverse outcomes. The first step toward disentangling this complex relationship is to identify the role of causal factors that precede the onset of psychiatric disorders so that subsequent steps can estimate the mediating power of psychiatric disorders in long-term outcomes. Successful documentation of these causal pathways requires the availability of longitudinal research in large cohorts with repeated measures of environmental exposures, assessment of social and family variables, genetic data, and mental health outcomes. This study will address these challenges by capitalizing on one of the few such cohorts available worldwide in the Chitwan Valley Family Study (CVFS) - a 20-year panel study of 10,000 individuals from 2,700 households in various sub-population groups.

Thus our study makes use of: (1) the CVFS panel study - with its exceptional measurement of social environment and detailed migration histories; (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 social environment and family: major depressive disorder, post-traumatic stress disorder, and alcohol use disorders. Our analyses will establish the role of community and gene-environment interactions in producing these common psychiatric disorders and, in the process, create a unique scientific resource with psychiatric phenotypes, demographic information, and biospecimens from CVFS participants. Our demographic analyses will identify key predictors of psychiatric disorders and we will use genome-wide genotyping and analyses that examine the roles of polygenic risk scores and genetic modifiers of environmental risk and resilience factors. The project will extend both the demography of mental health and psychiatric genetic findings from the European Diaspora to South Asian populations.

Funding Period: 09/19/2016 to 08/31/2017

Country of Focus: Nepal

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