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February 26, 2026BMC Psychiatry0 citationsOpen Access

Combinations of mental disorders and their association with mortality in the UK Biobank

VBVivian Boschesi BarrosAFAlexandre Dias Porto Chiavegatto Filho

Key Result

Combinations of probable lifetime mental disorders, especially including alcohol use disorder, substance use disorder, and psychotic experience, were associated with up to a 4.94-fold increase in mortality compared to others in a large UK cohort.

Key Points

  • The aim is to examine the association between combinations of mental disorders and mortality using UK Biobank data.
  • Analyzed data from approximately 160,000 UK Biobank participants
  • Completed a Mental Health Questionnaire
  • Utilized association rule mining to identify disorder combinations
  • Estimated age and sex-adjusted mortality rate ratios for each disorder and combination.
  • 30% of respondents had at least one probable lifetime mental disorder
  • Combinations typically included depression and/or anxiety
  • Higher mortality rates linked to combinations, especially with alcohol and substance use disorders
  • Highest mortality rate ratio was 4.94 for alcohol use disorder plus substance use disorder plus psychotic experience.

Study Design

Type

Observational (n=157,314)

Multicenter

Yes

Structured PICO

Are combinations of probable lifetime mental disorders associated with increased all-cause mortality in a middle-aged and elderly cohort?

P
Population
157,314 middle-aged and elderly adults (median age 58, 54% women) from the UK Biobank who completed the Mental Health Questionnaire.
I
Intervention
Combinations of probable lifetime mental disorders (depression, generalized anxiety disorder, psychotic experience, bipolar disorder, substance use disorder, alcohol use disorder) identified via the Mental Health Questionnaire.
C
Comparator
Participants who did not meet criteria for the specific probable mental disorder or combination being evaluated.
O
Outcome
Time from completing the Mental Health Questionnaire to all-cause death.hard clinical

Combinations of mental disorders, particularly those involving substance and alcohol use, are associated with significantly higher all-cause mortality than single disorders.

Main Result

Effect estimate: MRR 4.94 (95% CI 2.57-9.5)

Limitations

  • Mental disorders identified via self-reported questionnaire, not confirmed clinical diagnoses, possibly causing misclassification bias.
  • Lack of data on age at onset of disorders, introducing potential immortal time bias.
  • Healthy volunteer bias in UK Biobank limiting generalizability and likely underestimating mortality risk.
  • No adjustment for socioeconomic or health-related confounders, which may act as mediators.
  • Small numbers of deaths in some mental disorder combinations limited statistical power.
  • Did not formally test multiplicative interactions between mental disorders.
  • Retrospective assessment
  • Not fully validated modules
  • Self-reported diagnoses
  • Lack of information on age at onset (immortal time bias)
  • Healthy volunteer selection bias

Abstract

To explore patterns of combinations of mental disorders and their association with mortality using data from the UK Biobank, a large middle-aged and elderly cohort. This longitudinal cohort study analyzed data from approximately 160,000 UK Biobank participants who completed a Mental Health Questionnaire. We identified six probable lifetime mental disorders, examined their combinations using association rule mining, and estimated age and sex-adjusted mortality rate ratios (MRRs) for each disorder and combination. Combinations of mental disorders were found in approximately 30% of questionnaire completers identified with at least one probable lifetime mental disorder. Most combinations involved depression and/or anxiety. Combinations of mental disorders were generally associated with higher mortality, especially those including alcohol and substance use disorders. The highest MRR was observed for alcohol use disorder plus substance use disorder plus psychotic experience (MRR = 4.94, 95% CI 2.57–9.5). In a large middle-aged and elderly cohort in the UK, combinations of probable lifetime mental disorders identified via an online questionnaire were common and generally associated with higher mortality. Not applicable.

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Cite This Study

Barros et al. (2026) conducted an observational in Probable lifetime mental disorders identified via Mental Health Questionnaire (n=157,314). Combinations of probable lifetime mental disorders vs. Questionnaire completers without the specific mental disorder combination was evaluated on Time from Mental Health Questionnaire completion to all-cause mortality (MRR 4.94, 95% CI 2.57-9.5). Combinations of probable lifetime mental disorders, especially including alcohol use disorder, substance use disorder, and psychotic experience, were associated with up to a 4.94-fold increase in mortality compared to others in a large UK cohort.

synapsesocial.com/papers/699fe39d95ddcd3a253e792fhttps://doi.org/10.1186/s12888-026-07865-w
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