A direct test of the diathesis-stress model for depression
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The diathesis-stress theory for depression states that the effects of stress on the depression risk are dependent on the diathesis or vulnerability, implying multiplicative interactive effects on the liability scale. We used polygenic risk scores for major depressive disorder (MDD) calculated from the results of the most recent analysis from the Psychiatric Genomics Consortium as a direct measure of the vulnerability for depression in a sample of 5221 individuals from 3083 families. In the same we also had measures of stressful life events and social support and a depression symptom score, as well as DSM-IV MDD diagnoses for most individuals. In order to estimate the variance in depression explained by the genetic vulnerability, the stressors and their interactions, we fitted linear mixed models controlling for relatedness for the whole sample as well as stratified by sex. We show a significant interaction of the polygenic risk scores with personal life events (0.12% of variance explained, P-value=0.0076) contributing positively to the risk of depression. Additionally, our results suggest possible differences in the aetiology of depression between women and men. In conclusion, our findings point to an extra risk for individuals with combined vulnerability and high number of reported personal life events beyond what would be expected from the additive contributions of these factors to the liability for depression, supporting the multiplicative diathesis-stress model for this disease.
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The modal clinical presentation of people with personality disorders is a complaint of depression and significant proportions of people with depression have a comorbid personality disorder.
“Indeed, the modal clinical presentation of people with personality disorders is a complaint of depression 271,272 and significant proportions of people with depression have a comorbid personality disorder. 273”
From Time for united action on depression: a Lancet–World Psychiatric Association Commission (2022) · cites this paper as [271]
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- Authors
- Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Colodro-Conde, L., Couvy-Duchesne, B., Zhu, G., Coventry, W. L., Byrne, E. M., Gordon, S., Wright, M. J., Montgomery, G. W., Madden, P. A. F., Ripke, S., Eaves, L. J., Heath, A. C., Wray, N. R., Medland, S. E., & Martin, N. G.
- Affiliations
- QIMR Berghofer Medical Research Institute (AU)
- University of New England (AU)
- The University of Queensland (AU)
- Washington University in St. Louis (US)
- Broad Institute (US)
- Virginia Commonwealth University (US)
- ORCID
- Venue
- Molecular Psychiatry
- Published
- 2017-07-11
- Volume
- 23
- Issue
- 7
- Pages
- 1590-1596
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- PMC
- PMC5764823
- OpenAlex
- W2735059498
- Cited by
- 285
- References
- 81
- Citations by year
- 2026: 35 · 2025: 22 · 2024: 39 · 2023: 33 · 2022: 35 · 2021: 49 · 2020: 33 · 2019: 23 · 2018: 14 · 2017: 1
- FWCI
- 12.86
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Molecular Psychiatry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Digital Commons@Becker (Washington University School of Medicine) (submittedVersion, cc-by)
- RUNE (Research UNE) (submittedVersion, cc-by)
- Scopus (Elsevier) (submittedVersion, cc-by)
- Funders
- International Rett Syndrome Foundation
- Fundación Séneca
- QIMR Berghofer Medical Research Institute
- National Institutes of Health (AA007728)
- National Health and Medical Research Council (1103623)
- National Institute on Alcohol Abuse and Alcoholism (R37AA007728, R01AA010249, R01AA013321, R01AA013326, R01AA007535)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- diathesis-stress model, major depressive disorder, polygenic risk score, life events, social support, gene-environment interaction, sex differences in depression, genetic susceptibility
- MeSH terms
- Adult, Depression, Major Depressive Disorder, Disease Susceptibility, Female, Humans, Life Change Events, Male, Middle Aged, Risk Factors, Genetic Predisposition to Disease, Multifactorial Inheritance, Genome-Wide Association Study, Gene-Environment Interaction
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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