Karmel W Choi1,2,3,4, Chia-Yen Chen1,3,4,5, Robert J Ursano6, Xiaoying Sun7, Sonia Jain7, Ronald C Kessler8, Karestan C Koenen1,2,3,4, Min-Jung Wang2, Gary H Wynn6, Laura Campbell-Sills7, Murray B Stein7,9,10, Jordan W Smoller1,2,3,4. 1. Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA. 2. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA. 3. Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA. 4. Stanley Center for Psychiatric Research, Broad Institute, Boston, MA, USA. 5. Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA. 6. Uniformed Services University of the Health Sciences, Bethesda, MD, USA. 7. Department of Family Medicine and Public Health, University of California San Diego, La Jolla, CA, USA. 8. Department of Health Care Policy, Harvard Medical School, Boston, MA, USA. 9. Department of Psychiatry, University of California San Diego, La Jolla, CA, USA. 10. VA San Diego Healthcare System, San Diego, CA, USA.
Abstract
BACKGROUND: Whereas genetic susceptibility increases the risk for major depressive disorder (MDD), non-genetic protective factors may mitigate this risk. In a large-scale prospective study of US Army soldiers, we examined whether trait resilience and/or unit cohesion could protect against the onset of MDD following combat deployment, even in soldiers at high polygenic risk. METHODS: Data were analyzed from 3079 soldiers of European ancestry assessed before and after their deployment to Afghanistan. Incident MDD was defined as no MDD episode at pre-deployment, followed by a MDD episode following deployment. Polygenic risk scores were constructed from a large-scale genome-wide association study of major depression. We first examined the main effects of the MDD PRS and each protective factor on incident MDD. We then tested the effects of each protective factor on incident MDD across strata of polygenic risk. RESULTS: Polygenic risk showed a dose-response relationship to depression, such that soldiers at high polygenic risk had greatest odds for incident MDD. Both unit cohesion and trait resilience were prospectively associated with reduced risk for incident MDD. Notably, the protective effect of unit cohesion persisted even in soldiers at highest polygenic risk. CONCLUSIONS: Polygenic risk was associated with new-onset MDD in deployed soldiers. However, unit cohesion - an index of perceived support and morale - was protective against incident MDD even among those at highest genetic risk, and may represent a potent target for promoting resilience in vulnerable soldiers. Findings illustrate the value of combining genomic and environmental data in a prospective design to identify robust protective factors for mental health.
BACKGROUND: Whereas genetic susceptibility increases the risk for major depressive disorder (MDD), non-genetic protective factors may mitigate this risk. In a large-scale prospective study of US Army soldiers, we examined whether trait resilience and/or unit cohesion could protect against the onset of MDD following combat deployment, even in soldiers at high polygenic risk. METHODS: Data were analyzed from 3079 soldiers of European ancestry assessed before and after their deployment to Afghanistan. Incident MDD was defined as no MDD episode at pre-deployment, followed by a MDD episode following deployment. Polygenic risk scores were constructed from a large-scale genome-wide association study of major depression. We first examined the main effects of the MDD PRS and each protective factor on incident MDD. We then tested the effects of each protective factor on incident MDD across strata of polygenic risk. RESULTS: Polygenic risk showed a dose-response relationship to depression, such that soldiers at high polygenic risk had greatest odds for incident MDD. Both unit cohesion and trait resilience were prospectively associated with reduced risk for incident MDD. Notably, the protective effect of unit cohesion persisted even in soldiers at highest polygenic risk. CONCLUSIONS: Polygenic risk was associated with new-onset MDD in deployed soldiers. However, unit cohesion - an index of perceived support and morale - was protective against incident MDD even among those at highest genetic risk, and may represent a potent target for promoting resilience in vulnerable soldiers. Findings illustrate the value of combining genomic and environmental data in a prospective design to identify robust protective factors for mental health.
Entities:
Keywords:
Depression; genetics; longitudinal; polygenic risk; resilience; social support
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