Cited by 156Mental Health Treatment and AccessGenetic Associations and EpidemiologyTreatment of Major Depression

The DOI matches its Crossref record; 56 of the 58 references it cites were found in a registry or an index; 1 of the 30 sources its claims cite were checked for support.

Dependent Stressful Life Events and Prior Depressive Episodes in the Prediction of Major Depression

Open access
Kendler, Kenneth S., Gardner, Charles O.·2010·Archives of General Psychiatry

Abstract

CONTEXT: Most environmental risk factors for psychiatric disorders cannot be studied experimentally, making causal attributions difficult. Can we address this question by using together 2 major methods for causal inference: natural experiments and specialized statistical methods? OBJECTIVE: To determine the causal relationship between dependent stressful life events (dSLEs) and prior depressive episodes (PDEs) and major depression (MD). DESIGN: Assessment of risk factors and episodes of MD at interview. Statistical analyses used the co-twin control and propensity score-matching methods. SETTING: General community. PARTICIPANTS: Four thousand nine hundred ten male and female twins from the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders. MAIN OUTCOME MEASURE: Episodes of MD. RESULTS: We found that dSLEs were strongly associated with risk for MD in female (odds ratio [OR], 5.85) and male (4.55) twins in the entire sample and, at considerably lower levels, in female (2.29) and male (2.19) monozygotic twins discordant for dSLE exposure. A case-control sample matched on propensity score showed a moderate association in female (OR, 1.79) and male (1.53) twins. A PDE strongly predicted risk for MD in female (OR, 3.68) and male (5.20) twins in the entire sample. In monozygotic pairs discordant for exposure, the association was weaker in male (OR, 1.41) and absent in female (1.00) twins. A case-control sample matched on propensity score showed a moderate association between PDE and depressive episodes in male (OR, 1.58) and female twins (1.66). CONCLUSIONS: Although dSLEs have a modest causal effect on the risk for MD, a large proportion of the observed association is noncausal. The same pattern is seen for PDEs, although the causal impact is somewhat more tenuous. For environmental exposures in psychiatry that cannot be studied experimentally, co-twin control and propensity scoring methods--which have complementary strengths and weaknesses--can provide similar results, suggesting their joint use can help with the critical question of causal inference.

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TL;DR

Using 4,910 twins from the Virginia Adult Twin Study, the authors applied co-twin control and propensity-score matching to test whether dependent stressful life events (dSLEs) and prior depressive episodes (PDEs) causally increase risk for major depression (MD). Both exposures showed strong overall associations, but the causal effects were modest for dSLEs and weaker/more tentative for PDEs, with much of the association judged noncausal.

Key findings

  • dSLEs predicted MD in the entire sample (female OR 5.85; male OR 4.55), but the association fell in monozygotic twins discordant for dSLE exposure (female OR 2.29; male OR 2.19) and in propensity-score-matched samples (female OR 1.79; male OR 1.53).
  • PDEs predicted MD in the entire sample (female OR 3.68; male OR 5.20), but the association weakened in discordant monozygotic twins (male OR 1.41; female OR 1.00) and was moderate in propensity-score-matched samples (male OR 1.58; female OR 1.66).
  • The authors conclude dSLEs have a modest causal effect on MD risk, while a large proportion of the observed association is noncausal; the same pattern appears for PDEs, though the causal impact is “somewhat more tenuous.”

Methods

  • Participants were 4,910 male and female twins from the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders; same-sex female-female and male-male pairs were analyzed separately.
  • Risk factors were dSLEs (interviewer-rated probably/clearly dependent events) and PDEs; MD episodes were assessed by DSM-IV criteria, with dSLE-MD analyses examining onset within 3 months and PDE analyses using MM1/FF1 episodes to predict MM2/FF2 episodes.
  • Causal inference used co-twin control (twin pairs discordant for exposure, by zygosity) and propensity-score matching with 18 covariates for dSLE and 10 for PDE; analyses used logistic regression, multiple imputation, 90% CIs, and 1-tailed P values.

Limitations

  • Stated: power was limited, especially for discordant twin analyses and the rarer PDE exposure; low power may contribute to the lack of more definitive findings.
  • Stated: both methods assess a risk factor’s impact given the study population’s background exposures; a risk factor potent only in the presence of an uncommon background factor would typically produce a weak overall effect.
  • Evident from the text: the design is observational; co-twin control does not control environmental experiences unique to one twin, and propensity matching can over- or under-control covariates. Also, PDE propensity analyses had limited overlap (mean C statistics 0.840 in male and 0.857 in female twins), which the authors call higher than ideal.

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Crossref · 10.1001/archgenpsychiatry.2010.136

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33 Own result · 30 Own method · 20 Own interpretation · 11 No basis given · 6 No full text of the sources · 4 Not checked yet · 1 Not supported · accuracy not yet measured

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  • It may state two separate claims as one. 25
  • Probably not a substantial claim. 19
  • The quote only partly states this claim. 3
41 of 41
  • The paper relies on this without support.

    Twin pairs raised together are matched for their rearing environment and their genes (partly for dizygotic and completely for monozygotic pairs) although not for environmental experiences unique to each twin.

    “Twin pairs raised together are matched for their rearing environment and their genes (partly for dizygotic [DZ] and completely for monozygotic [MZ] pairs) although not for environmental experiences unique to each twin.”
  • The paper relies on this without support.

    A double-blind study to clarify the causal relationship of SLEs or PDEs with MD would not be feasible or ethical.

    “A double-blind study to clarify the causal relationship of either of these exposures with MD would not be feasible or ethical.”
  • The paper relies on this without support.

    The risk factor and outcome variables for PDEs are the same (both are episodes of MD) and should share most predictors.

    “Given these results and the fact that the risk factor and outcome variables were the same (ie, both are episodes of MD) and should share most predictors, the a priori probability that the observed association might be substantially noncausal is particularly high.”
  • The paper relies on this without support.

    Covariates used in propensity matching must be causes and not consequences of risk factor exposure.

    “Covariates have to be causes and not consequences of risk factor exposure.”
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  1. [14]Woodward J Making Things Happen 2003 New York, NY Oxford University Press

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Metadata

Authors
Kendler, K. S., & Gardner, C. O.
Affiliations
Virginia Commonwealth University (US)
Venue
Archives of General Psychiatry
Published
2010-11-01
Volume
67
Issue
11
Pages
1120
ISSN
0003-990X (ISSN-L)
OpenAlex
W2045667549
Cited by
156
References
58
Citations by year
2026: 4 · 2025: 8 · 2024: 10 · 2023: 8 · 2022: 5 · 2021: 5 · 2020: 12 · 2019: 12 · 2018: 14 · 2017: 7 · 2016: 13 · 2015: 17 · 2014: 8 · 2013: 13 · 2012: 12
FWCI
13.84
Type
journal article
Language
en
Open access
Locations
  • Archives of General Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion)
Funders
  • National Institutes of Health (DA-011287, MH‐068643)
  • National Institute of Mental Health (R01 MH049492, MH-49492, MH-068643, R01 MH068643)
  • National Institute on Drug Abuse (R01 DA011287, DA011287)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Mental Health Treatment and Access
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
Keywords
major depressive disorder, life events, environmental risk factors, causal inference, co-twin control, propensity score matching, monozygotic twins, sex differences, natural experiment
MeSH terms
Adult, Data Collection, Depressive Disorder, Major, Major Depressive Disorder, Diseases in Twins, Female, Humans, Life Change Events, Male, Middle Aged, Surveys and Questionnaires, Social Environment, Twins, Dizygotic, Twins, Monozygotic, Causality, Genetic Predisposition to Disease, Propensity Score

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