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Prospective study of polygenic risk, protective factors, and incident depression following combat deployment in US Army soldiers

Published online by Cambridge University Press:  15 April 2019

Karmel W. Choi*
Affiliation:
Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA Stanley Center for Psychiatric Research, Broad Institute, Boston, MA, USA
Chia-Yen Chen
Affiliation:
Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA Stanley Center for Psychiatric Research, Broad Institute, Boston, MA, USA Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA
Robert J. Ursano
Affiliation:
Uniformed Services University of the Health Sciences, Bethesda, MD, USA
Xiaoying Sun
Affiliation:
Department of Family Medicine and Public Health, University of California San Diego, La Jolla, CA, USA
Sonia Jain
Affiliation:
Department of Family Medicine and Public Health, University of California San Diego, La Jolla, CA, USA
Ronald C. Kessler
Affiliation:
Department of Health Care Policy, Harvard Medical School, Boston, MA, USA
Karestan C. Koenen
Affiliation:
Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA Stanley Center for Psychiatric Research, Broad Institute, Boston, MA, USA
Min-Jung Wang
Affiliation:
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
Gary H. Wynn
Affiliation:
Uniformed Services University of the Health Sciences, Bethesda, MD, USA
Laura Campbell-Sills
Affiliation:
Department of Family Medicine and Public Health, University of California San Diego, La Jolla, CA, USA
Murray B. Stein
Affiliation:
Department of Family Medicine and Public Health, University of California San Diego, La Jolla, CA, USA Department of Psychiatry, University of California San Diego, La Jolla, CA, USA VA San Diego Healthcare System, San Diego, CA, USA
Jordan W. Smoller
Affiliation:
Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA Stanley Center for Psychiatric Research, Broad Institute, Boston, MA, USA
*
Author for correspondence: Karmel Choi, PhD E-mail: KWCHOI@mgh.harvard.edu

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.

Type
Original Articles
Copyright
Copyright © Cambridge University Press 2019

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