Stressful life events and genetic liability to major depression: genetic control of exposure to the environment?
Abstract
Background Although overwhelming evidence suggests that genetic and environmental risk factors both contribute to the aetiology of major depression (MD), we know little of how these two risk factor domains inter-relate. In particular, can the genetic liability to MD increase the risk of experiencing stressful life events (SLEs)? Methods Using discrete time survival analysis in a population-based sample of 2164 female twins, we examined whether the risks for nine personal and three aggregate network SLEs were predicted by the level of genetic liability to MD, indexed by the lifetime history of MD in monozygotic and dizygotic co-twins. Results Genetic liability to MD was associated with a significantly increased risk for six personal SLEs (assault, serious marital problems, divorce/breakup, job loss, serious illness and major financial problems) and one network SLE (trouble getting along with relatives/friends). This effect was not due to SLEs occurring during depressive episodes. Similar results were found using structural equation twin modelling. In contrast to the pattern observed with MD, the genetic liability to alcoholism impacted on the risk for being robbed and having trouble with the law. Conclusion In women, genetic risk factors for MD increase the probability of experiencing SLEs in the interpersonal and occupational/financial domains. Genes can probably impact on the risk for psychiatric illness by causing individuals to select themselves into high risk environments…
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Genetic risk for MD increases exposures to certain classes of SLEs.
“prior evidence has shown that genetic risk for MD increases exposures to certain classes of SLEs”
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 & Karkowski-Shuman, 1997
The estimate that a minor proportion of genetic risk of depression reflects genetic effects linked to SLEs aligns with one previous study that found roughly 10-15% of the impact of genetic risk of depression was mediated through life experiences.
“This estimate aligns with that of one previous study, which found that roughly 10–15% of the impact of genetic risk of depression was mediated through life experiences (Kendler & Karkowski-Shuman, 1997).”
From Stressful life events increase the risk of major depressive episodes: A population-based twin study (2023) · cites this paper as Kendler & Karkowski-Shuman, 1997
Many factors predispose to both dependent stressful life events and major depression, including neuroticism, prior depressive episodes, and genetic risk for major depression.
“Many factors predispose to both dSLEs and MD, including neuroticism, PDEs, and genetic risk for MD.16–21”
From Dependent Stressful Life Events and Prior Depressive Episodes in the Prediction of Major Depression (2010) · cites this paper as [18]
Cites
Akaike, H. (1987) · Springer Series in Statistics · doi:10.1007/978-1-4612-1694-0_29 · Cited by 4,027 · see citing works
Methodology for Genetic Studies of Twins and Families
Neale, M. C., & Cardon, L. R. (1992) · doi:10.1007/978-94-015-8018-2 · Cited by 4,005 · see citing works
Smoking and Major Depression: A Causal Analysis
Kendler, K. S. (1993) · Archives of General Psychiatry · doi:10.1001/archpsyc.1993.01820130038007 · Cited by 792 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene
Caspi, A., Sugden, K., Moffitt, T. E., Taylor, A., Craig, I. W., Harrington, H., McClay, J., Mill, J., Martin, J., Braithwaite, A., et al. (2003) · Science · doi:10.1126/science.1083968 · Cited by 8,120 · see citing works
Hammen, C. (2005) · Annual Review of Clinical Psychology · doi:10.1146/annurev.clinpsy.1.102803.143938 · Cited by 2,979 · see citing works
Causal Relationship Between Stressful Life Events and the Onset of Major Depression
Kendler, K. S., Karkowski, L. M., & Prescott, C. A. (1999) · American Journal of Psychiatry · doi:10.1176/ajp.156.6.837 · Cited by 2,486 · see citing works
Self-citationGene-environment interplay and psychopathology: multiple varieties but real effects
Rutter, M., Moffitt, T. E., & Caspi, A. (2006) · Journal of Child Psychology and Psychiatry · doi:10.1111/j.1469-7610.2005.01557.x · Cited by 1,058 · see citing works
Behavioral activation treatment for depression: returning to contextual roots
Jacobson, N. S., Martell, C. R., & Dimidjian, S. (2001) · Clinical Psychology: Science and Practice · doi:10.1093/clipsy.8.3.255 · Cited by 1,011 · see citing works
Nesse, R. M. (2000) · Archives of General Psychiatry · doi:10.1001/archpsyc.57.1.14 · Cited by 891 · see citing works
Gender differences in emotional responses to interpersonal stress during adolescence
Rudolph, K. D. (2002) · Journal of Adolescent Health · doi:10.1016/s1054-139x(01)00383-4 · Cited by 785 · see citing works
The Genetics of Major Depression
Flint, J., & Kendler, K. S. (2014) · Neuron · doi:10.1016/j.neuron.2014.01.027 · Cited by 724 · see citing works
Self-citationGlucocorticoids, depression, and mood disorders: Structural remodeling in the brain
McEwen, B. S. (2005) · Metabolism · doi:10.1016/j.metabol.2005.01.008 · Cited by 687 · see citing works
Kaufman, J., Yang, B.-Z., Douglas-Palumberi, H., Grasso, D., Lipschitz, D., Houshyar, S., Krystal, J. H., & Gelernter, J. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2005.10.026 · Cited by 692 · see citing works
Holsboer, F. (1999) · Journal of Psychiatric Research · doi:10.1016/s0022-3956(98)90056-5 · Cited by 654 · see citing works
Jacobson, N. C., & Newman, M. G. (2017) · Psychological Bulletin · doi:10.1037/bul0000111 · Cited by 576 · see citing works
The influence of genetic factors and life stress on depression among adolescent girls
Silberg, J., Pickles, A., Rutter, M., Hewitt, J., Simonoff, E., Maes, H., Carbonneau, R., Murrelle, L., Foley, D., & Eaves, L. (1999) · Archives of General Psychiatry · doi:10.1001/archpsyc.56.3.225 · Cited by 398 · see citing works
Minimal phenotyping yields genome-wide association signals of low specificity for major depression
MDD Working Group of the Psychiatric Genomics Consortium, Cai, N., Revez, J. A., Adams, M. J., Andlauer, T. F. M., Breen, G., Byrne, E. M., Clarke, T.-K., Forstner, A. J., Grabe, H. J., et al. (2020) · Nature Genetics · doi:10.1038/s41588-020-0594-5 · Cited by 344 · see citing works
Self-citationAcute stress reduces reward responsiveness: Implications for depression
Bogdan, R., & Pizzagalli, D. A. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.03.037 · Cited by 364 · see citing works
Zalsman, G., Huang, Y.-Y., Oquendo, M. A., Burke, A. K., Hu, X.-Z., Brent, D. A., Ellis, S. P., Goldman, D., & Mann, J. J. (2006) · American Journal of Psychiatry · doi:10.1176/ajp.2006.163.9.1588 · Cited by 371 · see citing works
Life events and affective disorders
Paykel, E. S. (2003) · Acta Psychiatrica Scandinavica · doi:10.1034/j.1600-0447.108.s418.13.x · Cited by 368 · see citing works
Association Between Depression and Elevated C-Reactive Protein
Danner, M., Kasl, S. V., Abramson, J. L., & Vaccarino, V. (2003) · Psychosomatic Medicine · doi:10.1097/01.psy.0000041542.29808.01 · Cited by 341 · see citing works
Ormel, J., Oldehinkel, A. J., & Brilman, E. I. (2001) · American Journal of Psychiatry · doi:10.1176/appi.ajp.158.6.885 · Cited by 330 · see citing works
Genetic moderation of environmental risk for depression and anxiety in adolescent girls
Silberg, J., Rutter, M., Neale, M., & Eaves, L. (2001) · British Journal of Psychiatry · doi:10.1192/bjp.179.2.116 · Cited by 285 · see citing works
Etiology of depression comorbidity in combat-related PTSD: a review of the literature
Stander, V. A., Thomsen, C. J., & Highfill-McRoy, R. M. (2014) · Clinical Psychology Review · doi:10.1016/j.cpr.2013.12.002 · Cited by 271 · see citing works
Stress increases vulnerability to inflammation in the rat prefrontal cortex
de Pablos, R. M., Villarán, R. F., Argüelles, S., Herrera, A. J., Venero, J. L., Ayala, A., Cano, J., & Machado, A. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.0802-06.2006 · Cited by 215 · see citing works
de Pablos, R. M., Herrera, A. J., Espinosa-Oliva, A. M., Sarmiento, M., Muñoz, M. F., Machado, A., & Venero, J. L. (2014) · Journal of Neuroinflammation · doi:10.1186/1742-2094-11-34 · Cited by 201 · see citing works
Dependent Stressful Life Events and Prior Depressive Episodes in the Prediction of Major Depression
Kendler, K. S., & Gardner, C. O. (2010) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2010.136 · Cited by 156 · see citing works
“These variables (and, where available, the original scales and publications showing their association with MD) were (1) birth year, (2) mean parental warmth measured by the Parental Bonding Instrument,(33,34) (3) childhood sexual abuse,(35,36) (4) parental loss due to death or divorce in childhood,(37) (5) neuroticism…”
Self-citationArloth, J., Bogdan, R., Weber, P., Frishman, G., Menke, A., Wagner, K. V., Balsevich, G., Schmidt, M. V., Karbalai, N., Czamara, D., et al. (2015) · Neuron · doi:10.1016/j.neuron.2015.05.034 · Cited by 142 · see citing works
Consequences of multiple withdrawals from alcohol
Duka, T., Gentry, J., Malcolm, R., Ripley, T. L., Borlikova, G., Stephens, D. N., Veatch, L. M., Becker, H. C., & Crews, F. T. (2004) · Alcoholism: Clinical and Experimental Research · doi:10.1097/01.alc.0000113780.41701.81 · Cited by 142 · see citing works
Computational nosology and precision psychiatry
Friston, K. J., Redish, A. D., & Gordon, J. A. (2017) · Computational Psychiatry · doi:10.1162/cpsy_a_00001 · Cited by 126 · see citing works
Harkness, K. L., Alavi, N., Monroe, S. M., Slavich, G. M., Gotlib, I. H., & Bagby, R. M. (2010) · Journal of Abnormal Psychology · doi:10.1037/a0020629 · Cited by 116 · see citing works
Neuroticism, life events and mental health: Evidence for person-environment correlation
Van Os, J., Park, S. B. G., & Jones, P. B. (2001) · British Journal of Psychiatry · doi:10.1192/bjp.178.40.s72 · Cited by 96 · see citing works
Pathways to Suicide: An Integrative Approach
van Heeringen, K., Hawton, K., & G. Williams, J. M. (2000) · The International Handbook of Suicide and Attempted Suicide · doi:10.1002/9780470698976.ch14 · Cited by 83 · see citing works
The Genetics of Major Depression
Flint, J., & Kendler, K. S. (2014) · Neuron · doi:10.1016/j.neuron.2014.02.033 · Cited by 81 · see citing works
“Is it possible that the endogenous form of MD is more genetically determined than others? The short answer to that question is no; in fact, contrary to the hypothesis that subjects whose MD appears to be devoid of precipitating events should have increased genetic predisposition (indexed by greater family history), th…”
Self-citationOstiguy, C. S., Ellenbogen, M. A., Walker, C.-D., Walker, E. F., & Hodgins, S. (2011) · Psychological Medicine · doi:10.1017/s0033291711000523 · Cited by 62 · see citing works
Childhood adversities and adolescent depression: A matter of both risk and resilience
Oldehinkel, A. J., Ormel, J., Verhulst, F. C., & Nederhof, E. (2014) · Development and Psychopathology · doi:10.1017/s0954579414000534 · Cited by 62 · see citing works
Arnaldo, I., Corcoran, A. W., Friston, K. J., & Ramstead, M. J. D. (2022) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2022.104590 · Cited by 56 · see citing works
McEwen, B. S. (2004) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2004.6.2/bmcewen · Cited by 54 · see citing works
Accumulation of trauma over time and risk for depression in a twin sample
McCutcheon, V. V., Heath, A. C., Nelson, E. C., Bucholz, K. K., Madden, P. A. F., & Martin, N. G. (2009) · Psychological Medicine · doi:10.1017/s0033291708003759 · Cited by 54 · see citing works
Azadmarzabadi, E., Haghighatfard, A., & Mohammadi, A. (2018) · Psychogeriatrics · doi:10.1111/psyg.12312 · Cited by 46 · see citing works
McAdams, T. A., Gregory, A. M., & Eley, T. C. (2013) · Behavior Genetics · doi:10.1007/s10519-013-9591-0 · Cited by 50 · see citing works
“…and parental negativity share genetic variance with commonly occurring behavioural and emotional problems: Genetic overlap has been reported between negative life events and depression (Kendler and Karkowski-Shuman 1997), anxiety (Boer et al. 2002), and antisocial behaviour (Button et al. 2008).”
BackgroundWell-being and ill-being: shared environments, shared genes?
Nes, R. B., Czajkowski, N., R⊘ysamb, E., Reichborn-Kjennerud, T., & Tambs, K. (2008) · The Journal of Positive Psychology · doi:10.1080/17439760802399323 · Cited by 36 · see citing works
Stressful life events increase the risk of major depressive episodes: A population-based twin study
Bjørndal, L. D., Kendler, K. S., Reichborn-Kjennerud, T., & Ystrom, E. (2023) · Psychological Medicine · doi:10.1017/s0033291722002227 · Cited by 35 · see citing works
“This estimate aligns with that of one previous study, which found that roughly 10–15% of the impact of genetic risk of depression was mediated through life experiences (Kendler & Karkowski-Shuman, 1997).”
ResultSelf-citationPatten, S. B. (1999) · Medical Hypotheses · doi:10.1054/mehy.1998.0747 · Cited by 16 · see citing works
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
Kendler, K. S., Lönn, S. L., Sundquist, J., & Sundquist, K. (2025) · Psychological Medicine · doi:10.1017/s0033291725000583 · Cited by 1 · see citing works
Self-citation
- Authors
- KENDLER, K. S., & KARKOWSKI-SHUMAN, L.
- Affiliations
- Virginia Commonwealth University Medical Center (US)
- ORCID
- KENDLER, KENNETH S.
- Venue
- Psychological Medicine
- Publisher
- Cambridge University Press (CUP)
- Published
- 1997-05
- Volume
- 27
- Issue
- 3
- Pages
- 539-547
- ISSN
- 0033-2917 (ISSN-L)
- 1469-8978
- OpenAlex
- W2115182573
- Cited by
- 328
- References
- 3
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 7 · 2023: 5 · 2022: 6 · 2021: 10 · 2020: 7 · 2019: 7 · 2018: 10 · 2017: 9 · 2016: 8 · 2015: 12 · 2014: 17 · 2013: 12 · 2012: 10
- FWCI
- 5.65
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Psychological Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5k05mh001277-05)
- National Institute on Alcohol Abuse and Alcoholism (R01AA009095, AA-09095)
- National Institute of Mental Health (MH-01277, R01MH040828, MH 40828)
- 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
- Social Sciences › Psychology › Clinical Psychology › Child and Adolescent Psychosocial and Emotional Development
- Keywords
- major depressive disorder, life events, genetic susceptibility, gene-environment interaction, twin studies, women, alcoholism, interpersonal stress
- MeSH terms
- Adult, Depressive Disorder, Disease Susceptibility, Family Health, Female, Humans, Life Change Events, Longitudinal Studies, Models, Biological, Regression Analysis, Sampling Studies, Social Environment, Likelihood Functions, Odds Ratio, Survival Analysis
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.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
