Understanding the Connections Among Genes, Environment, Family Processes and Mental Health: 2015
Psychiatric Genetics & Mental Health · 2015–2020
This study set out to build a first-of-its-kind scientific resource connecting genetic risk, social environment, family life, and psychiatric disorders in a South Asian population. It integrated the Chitwan Valley Family Study (CVFS) — a long-running panel of communities, households and individuals in Western Chitwan Valley — with clinically validated psychiatric interviews and saliva-based DNA collection. The project focused on three of the most common and socially consequential psychiatric disorders: major depressive disorder (MDD), post-traumatic stress disorder (PTSD), and alcohol use disorder (AUD).
The research was designed to extend findings from psychiatric genetics and family demography — until then based largely on samples of European descent — to a South Asian setting, and to examine how genetic risk interacts with environmental exposure to shape mental health and long-term family outcomes.
The study drew its sample from the 151 CVFS sample neighborhoods of Western Chitwan Valley, an area chosen for its unusual ethnic diversity and long documented history of community, family and individual-level measurement spanning more than two decades. One neighborhood was later excluded after being displaced by a flood, leaving 150 active neighborhoods. All CVFS household members aged 15–59 were eligible for interview and saliva collection, released to the field in three successive groups as household registry data was completed.
The eligible sample ultimately totaled 11,518 individuals (out of 11,780 originally listed, with 262 found ineligible due to death, age, language barriers, or serious illness/disability).
Interviews used the World Health Organization’s World Mental Health Composite International Diagnostic Interview (WMH-CIDI), administered as a roughly 90-minute Computer Assisted Personal Interview (CAPI) via SurveyTrak and Blaise software, alongside a revised Life History Calendar (LHC) to aid recall of life events. Data collection began on February 22, 2016. An initial version of the questionnaire (Flow 1) produced unexpectedly low diagnostic rates, prompting the team to revise question wording and skip patterns; the resulting Flow 2 questionnaire was used from April 17, 2016 through July 31, 2019, with earlier Flow 1 respondents re-interviewed under Flow 2.
A total of 10,714 respondents completed the Flow 2 CIDI interview, for a final response rate of 93.02%. A dedicated Structured Clinical Interview for DSM-IV (SCID) sub-study, run in parallel with support from a psychiatric consultant, validated CIDI diagnoses against clinical assessment in 74 of 100 selected cases.
Saliva samples were collected using Oragene OGR-500 kits for genome-wide genotyping on the Illumina MEGA Array, targeting lifetime MDD, PTSD, and/or AUD cases (N=1,000), their parents (N=2,000), and unrelated controls (N=2,350). Of 11,125 kits received by ISER-N, 10,308 saliva samples were collected and logged, with 10,262 cases having both a completed Flow 2 interview and a saliva sample.
Because the Nepal Health Research Council did not permit export of raw saliva, DNA was extracted in Nepal at the Center for Molecular Dynamics Nepal (CMDN), Kathmandu, under a formal working agreement with ISER-N. Extracted DNA was shipped to the U.S. in six batches between October 2018 and February 2020, totaling 10,334 samples, for genotyping and long-term storage at the Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital.
Study-specific training was delivered in January 2016 by Yu-chieh (Jay) Lin of the University of Michigan, together with ISER-N’s Dr. Dirgha Ghimire (Co-Investigator), Study Manager Indra Chaudhary, and Data Manager Bishu Adhikari. Twenty-eight interviewers were certified for fieldwork following classroom training, field practice, and a certification test. At peak, the field team comprised 30 interviewers, 4 assistant supervisors, 2 supervisors, a study manager, and a data manager, maintaining a high interviewer-to-supervisor ratio to support close quality monitoring throughout data collection.
The study was designed from the outset to create a resource for the wider scientific community. De-identified phenotypic and genomic data are intended for deposit with the database of Genotypes and Phenotypes (dbGaP) and the international Psychiatric Genomics Consortium (PGC), with public-use files distributed through the Data Sharing for Demographic Research (DSDR) archive at the Inter-University Consortium for Political and Social Research (ICPSR), University of Michigan.
Conducted by the Institute for Social and Environmental Research-Nepal (ISER-N) in collaboration with the University of Michigan, Massachusetts General Hospital, and Harvard Medical School, with funding from the National Institutes of Health (NIH), USA.
Chitwan Valley Health and Stress Study (CVHSS)
Completed / December 2015 (NHRC approval) – February 2020 (data collection completion)
Completed
Quantitative Observational Study — Population-based Panel Survey with Biospecimen (Saliva/DNA) Collection