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Cited by 33Genetic Associations and EpidemiologyResilience and Mental HealthPosttraumatic Stress Disorder Research

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

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Choi, Karmel W., Chen, Chia-Yen, Ursano, Robert J., Sun, Xiaoying, Jain, Sonia, Kessler, Ronald C., Koenen, Karestan C., Wang, Min-Jung +5 more·2020·Psychological Medicine
DOI 10.1017/s0033291719000527PMC PMC8293300

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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.

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  • Previous studies have found genotype-environment interactions for SLEs and depression.

    “Previous studies have, however, found genotype-environment interactions for SLEs and depression (e.g. Choi et al. 2020; Mandelli & Serretti, 2013).”

    From Stressful life events increase the risk of major depressive episodes: A population-based twin study (2023) · cites this paper as Choi et al. 2020

    The Introduction (page unavailable) reports earlier findings that genetic susceptibility increases depression risk in the presence of stressful life events. But the citation presents Choi et al. as an example of a study that found such an interaction; its own Results (page unavailable) report non-interactive effects of polygenic risk and unit cohesion, not a genotype–stressful-life-event interaction. (LLM, conf=0.83)

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Authors
Choi, K. W., Chen, C.-Y., Ursano, R. J., Sun, X., Jain, S., Kessler, R. C., Koenen, K. C., Wang, M.-J., Wynn, G. H., Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Campbell-Sills, L., Stein, M. B., & Smoller, J. W.
Affiliations
  • Broad Institute (US)
  • Uniformed Services University of the Health Sciences (US)
  • University of California San Diego (US)
  • Harvard University (US)
Corresponding author
Choi, Karmel W.
ORCID
Venue
Psychological Medicine
Publisher
Cambridge University Press (CUP)
Published
2019-04-15
Volume
50
Issue
5
Pages
737-745
ISSN
  • 0033-2917 (ISSN-L)
  • 1469-8978
DOI
10.1017/s0033291719000527
PMC
PMC8293300
OpenAlex
W2952015503
Cited by
33
References
6
Citations by year
2026: 2 · 2025: 2 · 2024: 5 · 2023: 7 · 2022: 5 · 2021: 5 · 2020: 2 · 2019: 5
FWCI
2.56
Type
journal article
Language
en
Open access
Licence
www.cambridge.org/core/terms (unspecified)
Locations
  • Psychological Medicine (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
  • U.S. Department of Defense (HU00011520004)
  • U.S. Department of Health and Human Services (U01MH087981)
  • National Institutes of Health
  • Uniformed Services University of the Health Sciences
  • University of California, San Diego
  • Veterans Affairs San Diego Healthcare System
  • National Institute of Mental Health (U01MH109528, T32MH017119, NIMH T32, U01MH087981, K24MH094614, R01MH124871)
  • National Human Genome Research Institute (U01HG008685)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Social Sciences › Psychology › Clinical Psychology › Resilience and Mental Health
  • Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
Keywords
major depressive disorder, polygenic risk score, combat deployment, military personnel, unit cohesion, trait resilience, protective factors, genetic susceptibility, dose-response relationship, United States Army, Afghanistan deployment
MeSH terms
Military Deployment, Adult, Major Depressive Disorder, Depressive Disorder, Major, Female, Humans, Male, Mental Health, Military Personnel, Prospective Studies, Risk Factors, United States, Genetic Predisposition to Disease, Multifactorial Inheritance, Genome-Wide Association Study, Resilience, Psychological, Young Adult, Afghan Campaign 2001-, Protective Factors

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