Cited by 480Genetic Associations and EpidemiologyTreatment of Major DepressionBipolar Disorder and Treatment

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Genetic Risk, Number of Previous Depressive Episodes, and Stressful Life Events in Predicting Onset of Major Depression

Kendler, Kenneth S., Thornton, Laura M., Gardner, Charles O.·2001·American Journal of Psychiatry

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Abstract

OBJECTIVE: The association between stressful life events and the onset of major depression decreases as the number of previous depressive episodes increases. How do genetic risk factors for major depression impact on this "kindling" phenomenon? In particular, do those at high genetic risk exhibit an increase in the speed of kindling, or are they "prekindled"? METHOD: Using discrete-time survival analysis, the authors examined the interaction between genetic risk, number of previous depressive episodes, and life event exposure in the prediction of episodes of major depression in female-female twin pairs from a population-based registry. The twins were interviewed four times over a 9-year period, producing 92,521 person-months of exposure. RESULTS: The decline in the association between stressful life events and risk for major depression as the number of previous depressive episodes increased was strongest in those at low genetic risk and was weak to absent in those at high genetic risk. In the absence of previous depressive episodes, those at high genetic risk frequently experienced depressive episodes without major environmental stressors. CONCLUSIONS: Genetic risk factors for depression produce a "prekindling" effect rather than increase the speed of kindling. The "kindled" state, wherein depressive episodes occur with little provocation, may be reached by two pathways: many previous depressive episodes, perhaps driven by multiple adversities, and high genetic risk.

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Authors: Kendler, K. S., Thornton, L. M., & Gardner, C. O.
Affiliations: Virginia Commonwealth University (US)
ORCID: Kendler, Kenneth S.
Thornton, Laura M.
Venue: American Journal of Psychiatry
Publisher: American Psychiatric Association Publishing
Published: 2001-04-01
Volume: 158
Issue: 4
Pages: 582-586
ISSN: 0002-953X (ISSN-L)
1535-7228
DOI: 10.1176/appi.ajp.158.4.582
OpenAlex: W2141307005
Cited by: 480
References: 20
Citations by year: 2026: 3 · 2025: 3 · 2024: 6 · 2023: 1 · 2022: 8 · 2021: 10 · 2020: 7 · 2019: 11 · 2018: 13 · 2017: 48 · 2016: 19 · 2015: 21 · 2014: 19 · 2013: 23 · 2012: 28
FWCI: 11.50
Type: journal article
Language: en
Open access: closed
Locations: American Journal of Psychiatry (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
Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
Keywords: major depressive disorder, genetic risk, life events, kindling, depression onset, twin pairs, gene-environment interaction, adversity
MeSH terms: Adult, Depressive Disorder, Diseases in Twins, Female, Humans, Kindling, Neurologic, Life Change Events, Psychiatric Status Rating Scales, Recurrence, Registries, Risk Factors, Virginia, Genetic Predisposition to Disease

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Genetic Risk, Number of Previous Depressive Episodes, and Stressful Life Events in Predicting Onset of Major Depression

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