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

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
DOI 10.1001/archgenpsychiatry.2010.136PMC PMC3081880
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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.

AI snapshot

Written from the paper’s full text.

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.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1001/archgenpsychiatry.2010.136

Cites

56 of 56 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

1 of 30 cited sources checked · 0 supported · 1 flagged · accuracy not yet measured

  • Findingown data

    In male dizygotic twin pairs discordant for prior depressive episode exposure, the association between prior depressive episodes and depressive episode onset was OR 2.31 (90% CI, 0.96-5.91; P=.06).

    “the association between PDEs and depressive episode onset was considerably lower in discordant DZ pairs (OR, 2.31; 90% CI, 0.96–5.91; P=.06)”
    Quote in the paperSubstantial claim
  • Findingown data

    In a male case-control sample matched on propensity score, the association between prior depressive episode and depressive episodes was OR 1.58.

    “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).”
    Quote in the paperNot a substantial claim
  • Findingown data

    In male monozygotic twin pairs discordant for dependent stressful life event exposure, the association between exposure and depressive episode onset was OR 2.19 (90% CI, 1.25-3.93; P=.01).

    “in female (2.29) and male (2.19) monozygotic twins discordant for dSLE exposure”
    • Also stated in: § dSLEs AS A CAUSAL RISK FACTOR FOR AN MD EPISODE · plain
      “lower still in discordant MZ pairs (2.19; 1.25–3.93; P=.01)”
    Quote in the paperSubstantial claim
  • Findingown data

    In discordant MZ pairs, the association between a PDE and a subsequent depressive episode disappeared entirely (OR, 1.00; 90% CI, 0.45-2.23; P=.99).

    “Compared with the results in the entire sample, the association between a PDE and a subsequent depressive episode was considerably lower in discordant DZ pairs (OR, 2.04; 90% CI, 0.97–4.47; P=.06) and disappeared entirely in discordant MZ pairs (1.00; 0.45–2.23; P=.99).”
    Quote in the paperSubstantial claim
  • Findingown data

    In male monozygotic twin pairs discordant for prior depressive episode exposure, the association between prior depressive episodes and depressive episode onset was OR 1.41 (90% CI, 0.64-3.14; P=.24).

    “In monozygotic pairs discordant for exposure, the association was weaker in male (OR, 1.41) and absent in female (1.00) twins.”
    • Also stated in: § PDEs AS CAUSAL RISK FACTORS FOR SUBSEQUENT DEPRESSIVE EPISODES · plain
      “lower still in discordant MZ pairs (1.41; 0.64–3.14; P=.24).”
    Quote in the paperSubstantial claim
  • May combine two claims. 25
  • Classified as probably not a substantial claim. 19
  • The quote only partly states this claim. 3

  • May combine two claims.

    Premisecitation

    Increased rates of major depression follow dependent stressful life events and prior depressive episodes.

    “Increased rates of MD follow dSLEs7–9 and PDEs.10–12”
    Quote in the paperSubstantial claim1 of 6 sources checked
    • cites [7] Williamson DE Birmaher B Anderson BP al-Shabbout M Ryan ND Stressful life events in depressed adolescents: the role of dependent events during the depressive episode J Am Acad Child Adolesc Psychiatry 1995 34 5 591 598 7775354 source

      The source is cited for the dSLE portion of the sentence, not the prior-depressive-episode portion. Its Abstract reports that depressed adolescents had more dependent stressful life events; the Discussion says most assessed events occurred during an existing depressive episode and that the study could not determine whether events preceded depression onset. It therefore does not support the claimed direction that increased rates of major depression follow dSLEs. (LLM, conf=0.86)

      Checked by a reasoning model — may be wrong.

      Experimental — accuracy not yet measured
    • cites [8] Kessler RC The effects of stressful life events on depression Annu Rev Psychol 1997 48 191 214 9046559 source
    • cites [9] Surtees PG Miller PM Ingham JG Kreitman NB Rennie D Sashidharan SP Life events and the onset of affective disorder: a longitudinal general population study J Affect Disord 1986 10 1 37 50 2939122 source
    • cites [10] Sjöholm L Lavebratt C Forsell Y A multifactorial developmental model for the etiology of major depression in a population-based sample J Affect Disord 2009 113 1–2 66 76 18558436 source
    • cites [11] Kendler KS Gardner CO Prescott CA Toward a comprehensive developmental model for major depression in women Am J Psychiatry 2002 159 7 1133 1145 12091191 source
    • cites [12] Kendler KS Gardner CO Prescott CA Toward a comprehensive developmental model for major depression in men Am J Psychiatry 2006 163 1 115 124 16390898 source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    The propensity score analysis produced a mean C statistic of 0.840.

    “Our propensity score analysis produced a mean C statistic of 0.840, which is higher than ideal.”
    Quote in the paperNot a substantial claim

  • The quote only partly states this claim.

    Findingown data

    In a female case-control sample matched on propensity score, the odds ratio between dependent stressful life event exposure and a depressive outcome was 1.79 (90% CI, 1.33-2.41; P=.001).

    “A case-control sample matched on propensity score showed a moderate association in female (OR, 1.79) and male (1.53) twins.”
    • Also stated in: § dSLEs AS A CAUSAL RISK FACTOR FOR AN MD EPISODE · plain
      “The OR between dSLE exposure and a depressive outcome in this sample was 1.79 (90% CI, 1.33–2.41; P=.001).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    When DZ and MZ twin pairs discordant for dSLE exposure were examined, the association with MD fell substantially but remained statistically significant in both groups.

    “When we examined DZ and MZ twin pairs discordant for dSLE exposure, the association with MD fell substantially but remained statistically significant in both groups.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The OR observed in the propensity score analysis was similar and statistically significant in both male and female twins but substantially lower than that observed in the general population.

    “The OR observed in the propensity score analysis was similar and statistically significant in both male and female twins but also substantially lower than that observed in the general population.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    None of the 4 resulting analyses (2 twin types in male and female twins) achieved statistical significance, although 2 of them produced trends suggesting a causal relationship.

    “None of the 4 resulting analyses (2 twin types in male and female twins) achieved statistical significance, although 2 of them produced trends suggesting a causal relationship.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    The same pattern is seen for prior depressive episodes, although the causal impact is somewhat more tenuous.

    “The same pattern is seen for PDEs, although the causal impact is somewhat more tenuous.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: 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.

  • May combine two claims.

    Interpretationown data

    Dependent stressful life events have a modest causal effect on the risk for major depression, and a large proportion of the observed association is noncausal.

    “Although dSLEs have a modest causal effect on the risk for MD, a large proportion of the observed association is noncausal.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: 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.

  • May combine two claims. The quote only partly states this claim.

    Study design and conductown data

    In the male propensity analysis for dependent stressful life events, the mean C statistic across 10 imputations was 0.711, indicating good overlap in propensity scores between exposed and unexposed groups.

    “we obtained a mean C statistic across the 10 imputations of 0.711, which indicates a good degree of overlap in propensity scores between the exposed and unexposed groups.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    Zygosity was determined by discriminate function analyses using "twin questions" validated against DNA genotyping.

    “Zygosity was determined by discriminate function analyses using “twin questions” validated against DNA genotyping.28”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [28] Kendler KS Prescott CA A population-based twin study of lifetime major depression in men and women [published correction appears in Arch Gen Psychiatry. 2000;57(1):94–95] Arch Gen Psychiatry 1999 56 1 39 44 9892254 source

  • May combine two claims. The quote only partly states this claim.

    Study design and conductown data

    In the female propensity analysis for dependent stressful life events, the mean C statistic was 0.713, indicating substantial overlap in propensity scores between cases and controls.

    “Our propensity analysis achieved a mean C statistic of 0.713, indicating a substantial degree of overlap in propensity scores between cases and controls.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductown data

    The DZ and MZ pairs discordant for a PDE in the year before the FF1 interview had covariate imbalance on 4 variables: for DZ pairs, history of MD, neuroticism, self-esteem, and SLEs; for MZ pairs, neuroticism, self-esteem, marital quality, and SLEs.

    “The DZ and MZ pairs discordant for a PDE in the year before our FF1 interview had covariate imbalance on 4 variables: a history of MD, neuroticism, self-esteem, and SLEs for DZ pairs and neuroticism, self-esteem, marital quality, and SLEs for MZ pairs.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    The propensity score analysis obtained matched controls for a mean of 160.3 of 162 cases.

    “we were successful in obtaining matched controls for a mean of 160.3 of 162 cases.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductcitation

    The study created 10 imputed data sets for analysis, and the results were combined with estimates and standard errors calculated as described by Rubin and Li et al.

    “We created 10 imputed data sets for analysis, and the results were combined with estimates and standard errors calculated as described by Rubin51 and Li et al.52”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Rubin51

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites Li et al. [52] Li KH Raghunathan TE Rubin DB Large-sample significance levels from multiply imputed data using moment-based statistics and an F-reference distribution J Am Stat Assoc 1991 86 416 1065 1073

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Confidence intervals and P values in the study are based on profile likelihoods.

    “Confidence intervals and P values are based on profile likelihoods.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    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.

    “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.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: 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.

  • May combine two claims.

    Study design and conductown data

    Test-retest and interrater reliabilities for dependence of stressful life events were rs=0.77/κ=0.63 and rs=0.89/κ=0.79, respectively.

    “Using the Spearman correlation (rs) and weighted kappa (κ),31 we determined the test-retest and interrater reliabilities to be rs=0.77/κ=0.63 and rs=0.89/κ=0.79, respectively.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [31] Fleiss JS Cohen J Everett BS Large sample standard errors of kappa and weighted kappa Psychol Bull 1969 72 323 327

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductreasoning

    Because of clear a priori expectations that dependent stressful life events and prior depressive episodes should increase the risk for major depression, the study presents 1-tailed P values and 90% confidence intervals.

    “Because of clear a priori expectations that dSLEs and PDEs should increase the risk for MD, we present 1-tailed P values and 90% confidence intervals (CIs).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductown data

    The study repeated all analyses in matched samples using conditional logistic regression and found very similar results.

    “We repeated all analyses in our matched samples using conditional logistic regression and found very similar results.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductown data

    Across 10 iterations, the propensity analysis obtained matched controls for 170.2 of the 184 cases, with no covariate imbalance between the 2 groups.

    “Indeed, we obtained, on average across our 10 iterations, matched controls for 170.2 of the 184 cases, with no covariate imbalance between the 2 groups.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    If the association between a risk factor and disease is causal, reducing risk factor exposure will reduce rates of disease; if the association is noncausal, altering risk factor exposure will not affect illness rates.

    “As articulated by the counterfactual/interventionist theories of causation,13–15 if the association is causal, reducing risk factor exposure will reduce rates of disease. If the association is noncausal, altering risk factor exposure will not affect illness rates.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [13] Kendler KS Campbell J Interventionist causal models in psychiatry: repositioning the mind-body problem Psychol Med 2009 39 6 881 887 18845010 source
    • cites [14] Woodward J Making Things Happen 2003 New York, NY Oxford University Press

      Not checked in the free run.

    • cites [15] Pearl J Causality Models, Reasoning, and Inference 2000 Cambridge, England Cambridge University Press

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Because numerous risk factors for major depression, including genes and childhood adversities, have long-lasting effects, the tendency for major depression to recur could arise without one depressive episode having a causal effect on the next.

    “Because numerous risk factors for MD—including genes and childhood adversities—have long-lasting effects,11,12,22,23 the tendency for MD to recur could arise without one depressive episode having a causal effect on the next.”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [11] Kendler KS Gardner CO Prescott CA Toward a comprehensive developmental model for major depression in women Am J Psychiatry 2002 159 7 1133 1145 12091191 source
    • cites [12] Kendler KS Gardner CO Prescott CA Toward a comprehensive developmental model for major depression in men Am J Psychiatry 2006 163 1 115 124 16390898 source
    • cites [22] Kendler KS Neale MC Kessler RC Heath AC Eaves LJ A longitudinal twin study of 1-year prevalence of major depression in women Arch Gen Psychiatry 1993 50 11 843 852 8215810 source
    • cites [23] Fergusson DM Mullen PE Childhood Sexual Abuse: An Evidence Based Perspective 1999 Thousand Oaks, CA Sage Publications Inc

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationreasoning

    The congruence of these findings substantially increases the probability of their veracity.

    “The congruence of these findings substantially increases the probability of their veracity.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductown data

    The propensity method worked well in obtaining matched controls for the exposed cases and produced ORs that were modest and similar in male and female twins (1.6-1.7).

    “Our propensity method worked well in obtaining matched controls for our exposed cases and produced ORs that were modest and similar in male and female twins (1.6–1.7).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    In both sexes, the 2 methods produced broadly similar results showing a moderate causal impact of dSLEs on risk for MD.

    “In both sexes, these 2 methods have produced broadly similar results showing a moderate causal impact of dSLEs on risk for MD.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given

    The co-twin control and propensity analyses assess the impact of a risk factor given the background exposures of the study population.

    “Second, the co-twin control and propensity analyses assess the impact of a risk factor given the background exposures of the study population.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    The longitudinal twin cohort has a particularly rich set of depression-related risk factors.

    “Although this is not realistic for any behavioral outcome, our longitudinal twin cohort has a particularly rich set of depression-related risk factors.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    Although the observed associations were largely noncausal, a moderate causal effect of dSLEs on MD was convincingly demonstrated, whereas the causal impact of PDEs was somewhat weaker and more tentative.

    “Although the observed associations were largely noncausal, a moderate causal effect of dSLEs on MD was convincingly demonstrated, whereas the causal impact of PDEs was somewhat weaker and more tentative.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Previous analyses in this and other samples found that, in the presence of many covariates, PDEs modestly predict risk for future depressive episodes.

    “This interpretation is consistent with previous analyses in this11,12 and other10 samples in which, in the presence of many covariates, PDEs modestly predict risk for future depressive episodes.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [11] Kendler KS Gardner CO Prescott CA Toward a comprehensive developmental model for major depression in women Am J Psychiatry 2002 159 7 1133 1145 12091191 source
    • cites [12] Kendler KS Gardner CO Prescott CA Toward a comprehensive developmental model for major depression in men Am J Psychiatry 2006 163 1 115 124 16390898 source
    • cites [10] Sjöholm L Lavebratt C Forsell Y A multifactorial developmental model for the etiology of major depression in a population-based sample J Affect Disord 2009 113 1–2 66 76 18558436 source

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Premisenone given

    The co-twin control method provides excellent matching for all shared environmental exposures and, for MZ twins, all genes.

    “The co-twin control method provides excellent matching for all shared environmental exposures and, for MZ twins, all genes.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    The co-twin control and propensity analyses each suggest that dSLEs have a moderate true causal effect on the risk for MD.

    “The co-twin control and propensity analyses each suggest that dSLEs have a moderate true causal effect on the risk for MD.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    The propensity method worked as expected in obtaining controls well matched to the cases.

    “Our propensity method worked as expected in obtaining controls well matched to our cases.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductown data

    MZ twin pairs discordant for dSLE exposure were very similar on the covariates, differing in male and female twins only in marital quality.

    “Of interest, MZ twin pairs discordant for dSLE exposure were very similar on our covariates, differing in male and female twins only in marital quality.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    Low power may contribute to the lack of more definitive findings.

    “Low power may contribute to the lack of more definitive findings.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Premisenone given

    If a risk factor is causally potent only in the presence of an uncommon background factor, it will typically produce a weak overall effect.

    “If a risk factor is causally potent only in the presence of an uncommon background factor, it will typically produce a weak overall effect.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given

    If all relevant factors that influence risk exposure were known and measured, the propensity method would provide accurate and unbiased estimates of causal effects.

    “If we knew of and measured all the relevant factors that influence risk exposure, the propensity method would provide accurate and unbiased estimates of causal effects.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    The association between dSLEs and subsequent depressive episodes may not be entirely causal and may be at least partly mediated via covariates.

    “In our detailed set of covariates, those exposed to dSLEs (cases) frequently differed from those who were unexposed (controls), immediately raising concern that the association between dSLEs and subsequent depressive episodes may not be entirely causal and may instead be at least partly mediated via these covariates along paths a and b in Figure 1.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S2 (checkable). May combine two claims.

    Premisenone given

    Clarifying causal processes is problematic in psychiatric epidemiology, in which controlled trials are often impossible.

    “Clarifying causal processes is problematic in psychiatric epidemiology, in which controlled trials are often impossible.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S2 (checkable).

    Premisecitation

    Our confidence in scientific results should increase when similar answers are obtained by different methods, especially when these 2 methods have different strengths and weaknesses.

    “Our confidence in scientific results should increase when similar answers are obtained by different methods, especially when these 2 methods have different strengths and weaknesses, for example, in the congruent evidence of genetic influences on schizophrenia from twin and adoption studies.53”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [53] Kendler KS Diehl SR The genetics of schizophrenia: a current, genetic-epidemiologic perspective Schizophr Bull 1993 19 2 261 285 8322035 source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisereasoning

    If covariates that influence risk factor exposure and outcome are left out of propensity matching, this could result in an overestimation of causal effects.

    “If covariates that influence risk factor exposure and outcome are left out of propensity matching, this could also result in an overestimation of causal effects.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    Dependent SLEs are, at least in part, exogenous risk factors that proved relatively easy to control for, as demonstrated by the very low rate of covariate imbalance in the discordant MZ twins.

    “Dependent SLEs are, at least in part, exogenous risk factors that proved relatively easy to control for, as demonstrated by the very low rate of covariate imbalance in our discordant MZ twins.”
    Quote in the paperSubstantial claim
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.”
4 of 4

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?

  • Findings from several genetically informative studies indicate that associations between SLEs and depression in part reflect the causal influence of exposure on depression risk.

    “Findings from several genetically informative studies have indicated that the associations between SLEs and depression in part reflect the causal influence of exposure on depression risk (Kendler et al., 1999a; Kendler & Aggen, 2014; Kendler & Gardner, 2010).”

    From Stressful life events increase the risk of major depressive episodes: A population-based twin study (2023) · cites this paper as Kendler & Gardner, 2010

  • The co-twin control design is unable to control for non-shared confounders that only affect one twin, which can bias estimated effects.

    “Although the co-twin control design increases control over genetic and shared environmental confounders, it is unable to control for non-shared confounders that only affect one twin, which can bias estimated effects (Frisell et al., 2012; Kendler & Gardner, 2010).”

    From Stressful life events increase the risk of major depressive episodes: A population-based twin study (2023) · cites this paper as Kendler & Gardner, 2010

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Male dSLE exposure is assigned to different interview years

    Major

    The male dSLE results place exposure in the year before MM1, but the methods say stressful life events were assessed for the year before MM2. These are different exposure periods for the reported association.

  • Female PDE outcome is assigned to different interview waves

    Minor

    The methods identify episodes reported at FF2 as the outcome of the PDE analysis, whereas the female results describe the outcome as episodes in the year before FF4.

2 of 2

Cites

Flagged first, then by citations

2 of the 58 references couldn’t be matched to a known paper.

Research works printed but not linked: 1

  1. [14]Woodward J Making Things Happen 2003 New York, NY Oxford University Press

Cited by

Sorted by citations

Related

Authors
Kendler, K. S., & Gardner, C. O.
Affiliations
Virginia Commonwealth University (US)
ORCID
Kendler, Kenneth S.
Venue
Archives of General Psychiatry
Publisher
American Medical Association (AMA)
Published
2010-11-01
Volume
67
Issue
11
Pages
1120
ISSN
0003-990X (ISSN-L)
DOI
10.1001/archgenpsychiatry.2010.136
PMC
PMC3081880
OpenAlex
W2045667549
Semantic Scholar
dab89f6651d38065df4ad8a91faa4ac2eb753315
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
  • Social Sciences › Psychology › Social Psychology › Mental Health Treatment and Access
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Health Sciences › Medicine › Pharmacology › 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

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.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-20.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-20.

Cited sources are checked by gpt-6-sol.

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 ›

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