Stressful life events, genetic liability, and onset of an episode of major depression in women
Abstract
Objective This study was undertaken to clarify how genetic liability and stressful life events interact in the etiology of major depression. Method Information about stressful life events and onset of major depressive episodes in the past year was collected in a population-based sample of female-female twin pairs including 2,164 individuals, 53,215 person-months of observation, and 492 onsets of depression. Results Nine "personal" and three aggregate "network" stressful events significantly predicted onset of major depression in the month of occurrence, four of which predicted onset with an odds ratio of > 10 and were termed "severe": death of a close relative, assault, serious marital problems, and divorce/breakup. Genetic liability also had a significant impact on risk of onset of depression. For severe stressful events, as well as for 10 of the 12 individual stressful events, the best-fitting model for the joint effect of stressful events and genetic liability on onset of major depression suggested genetic control of sensitivity to the depression-inducing effects of stressful life events. In individuals at lowest genetic risk (monozygotic twin, co-twin unaffected), the probability of onset of major depression per month was predicted to be 0.5% and 6.2%, respectively, for those unexposed and exposed to a severe event. In those at highest genetic risk (monozygotic twin, co-twin affected), these probabilities were 1.1% and 14.6%, respectively. Linear regression analysis indic…
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Several prior twin studies show evidence of increased sensitivity to the depressogenic effects of environmental exposures in those with high genetic risk.
“several prior twin studies, assessing a range of environmental adversities, show evidence of increased sensitivity to the depressogenic effects of these environmental exposures in those with high genetic risk”
From The development of an environmental risk score using Swedish National Registers and its impact on subsequent episodes of major depression (2025) · cites this paper as Kendler et al., 1995
With respect to MD, genes in part act on liability by altering the sensitivity to the effects of environmental stressors.
“suggesting that, with respect to MD, genes in part act on liability by altering the sensitivity to the effects of environmental stressors”
From The development of an environmental risk score using Swedish National Registers and its impact on subsequent episodes of major depression (2025) · cites this paper as Kendler et al., 1995
Interrater reliability (κ) values for the occurrence and dating of the study's stressful life event categories were 0.93 and 0.82, respectively.
“Interrater reliability (κ) values for the occurrence and dating of our SLE categories were 0.93 and 0.82, respectively.30”
From Dependent Stressful Life Events and Prior Depressive Episodes in the Prediction of Major Depression (2010) · cites this paper as [30]
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Clarke, T.-K., Zeng, Y., Navrady, L., Xia, C., Haley, C., Campbell, A., Navarro, P., Amador, C., Adams, M. J., Howard, D. M., et al. (2018) · Wellcome Open Research · doi:10.12688/wellcomeopenres.13893.1 · Cited by 16 · see citing works
- Authors
- Kendler, K. S., Kessler, R. C., Walters, E. E., MacLean, C. J., Neale, M. C., Heath, A. C., & Eaves, L. J.
- Affiliations
- Virginia Commonwealth University (US)
- Venue
- American Journal of Psychiatry
- Published
- 1995-06-01
- Volume
- 152
- Issue
- 6
- Pages
- 833-842
- ISSN
- 0002-953X (ISSN-L)
- 1535-7228
- OpenAlex
- W2174681609
- Cited by
- 1,063
- References
- 1
- Citations by year
- 2026: 15 · 2025: 15 · 2024: 15 · 2023: 12 · 2022: 17 · 2021: 21 · 2020: 22 · 2019: 25 · 2018: 28 · 2017: 69 · 2016: 30 · 2015: 45 · 2014: 47 · 2013: 54 · 2012: 49
- FWCI
- 12.50
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01hd026746-05)
- National Institute of Mental Health (R01MH040828, MH 40828)
- National Institute of Neurological Disorders and Stroke (NS-31564, R01NS031564)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD 26746)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Social Sciences › Psychology › Clinical Psychology › Child and Adolescent Psychosocial and Emotional Development
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- major depressive disorder, life events, genetic susceptibility, women, monozygotic twins, co-twin control, gene-environment interaction, depression onset, assault, marital problems, divorce, twin pairs
- MeSH terms
- Adult, Depressive Disorder, Diseases in Twins, Female, Genotype, Humans, Life Change Events, Probability, Regression Analysis, Risk Factors, Social Support, Twins, Dizygotic, Twins, Monozygotic, Odds Ratio
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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