Impact of mental disorders on clinical outcomes of physical diseases: an umbrella review assessing population attributable fraction and generalized impact fraction
Open accessAbstract
Empirical evidence indicates a significant bidirectional association between mental disorders and physical diseases, but the prospective impact of mental disorders on clinical outcomes of physical diseases has not been comprehensively outlined. In this PRISMA‐ and COSMOS‐E‐compliant umbrella review, we searched PubMed, PsycINFO, Embase, and Joanna Briggs Institute Database of Systematic Reviews and Implementation Reports, up to March 15, 2022, to identify systematic reviews with meta‐analysis that examined the prospective association between any mental disorder and clinical outcomes of physical diseases. Primary outcomes were disease‐specific mortality and all‐cause mortality. Secondary outcomes were disease‐specific incidence, functioning and/or disability, symptom severity, quality of life, recurrence or progression, major cardiac events, and treatment‐related outcomes. Additional inclusion criteria were further applied to primary studies. Random effect models were employed, along with I 2 statistic, 95% prediction intervals, small‐study effects test, excess significance bias test, and risk of bias (ROBIS) assessment. Associations were classified into five credibility classes of evidence (I to IV and non‐significant) according to established criteria, complemented by sensitivity and subgroup analyses to examine the robustness of the main analysis. Statistical analysis was performed using a new package for conducting umbrella reviews (https://metaumbrella.org). Population attributable fraction (PAF) and generalized impact fraction (GIF) were then calculated for class I‐III associations. Forty‐seven systematic reviews with meta‐analysis, encompassing 251 non‐overlapping primary studies and reporting 74 associations, were included (68% were at low risk of bias at the ROBIS assessment). Altogether, 43 primary outcomes (disease‐specific mortality: n=17; all‐cause mortality: n=26) and 31 secondary outcomes were investigated. Although 72% of associations were statistically significant (p<0.05), only two showed convincing (class I) evidence: that between depressive disorders and all‐cause mortality in patients with heart failure (hazard ratio, HR=1.44, 95% CI: 1.26‐1.65), and that between schizophrenia and cardiovascular mortality in patients with cardiovascular diseases (risk ratio, RR=1.54, 95% CI: 1.36‐1.75). Six associations showed highly suggestive (class II) evidence: those between depressive disorders and all‐cause mortality in patients with diabetes mellitus (HR=2.84, 95% CI: 2.00‐4.03) and with kidney failure (HR=1.41, 95% CI: 1.31‐1.51); that between depressive disorders and major cardiac events in patients with myocardial infarction (odds ratio, OR=1.52, 95% CI: 1.36‐1.70); that between depressive disorders and dementia in patients with diabetes mellitus (HR=2.11, 95% CI: 1.77‐2.52); that between alcohol use disorder and decompensated liver cirrhosis in patients with hepatitis C (RR=3.15, 95% CI: 2.87‐3.46); and that between schizophrenia and cancer mortality in patients with cancer (standardized mean ratio, SMR=1.74, 95% CI: 1.41‐2.15). Sensitivity/subgroup analyses confirmed these results. The largest PAFs were 30.56% (95% CI: 27.67‐33.49) for alcohol use disorder and decompensated liver cirrhosis in patients with hepatitis C, 26.81% (95% CI: 16.61‐37.67) for depressive disorders and all‐cause mortality in patients with diabetes mellitus, 13.68% (95% CI: 9.87‐17.58) for depressive disorders and major cardiac events in patients with myocardial infarction, 11.99% (95% CI: 8.29‐15.84) for schizophrenia and cardiovascular mortality in patients with cardiovascular diseases, and 11.59% (95% CI: 9.09‐14.14) for depressive disorders and all‐cause mortality in patients with kidney failure. The GIFs confirmed the preventive capacity of these associations. This umbrella review demonstrates that mental disorders increase the risk of a poor clinical outcome in several physical diseases. Prevention targeting mental disorders – particularly alcohol use disorders, depressive disorders, and schizophrenia – can reduce the incidence of adverse clinical outcomes in people with physical diseases. These findings can inform clinical practice and trans‐speciality preventive approaches cutting across psychiatric and somatic medicine.
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Individuals with diabetes and comorbid MDD have an increased risk of dementia (HR 2.69, 95% CI 1.77-4.07) compared to individuals with diabetes only.
“For example, a prospective study reported that individuals with diabetes and comorbid MDD had an increased risk of dementia (HR: 2.69, 95% CI: 1.77-4.07) compared to individuals with diabetes only41,59.”
From Comorbidity between major depressive disorder and physical diseases: a comprehensive review of epidemiology, mechanisms and management (2023) · cites this paper as [41]
The Discussion reports an increased risk of dementia associated with depressive disorders in patients with diabetes. However, the paper reports HR 2.11 (95% CI 1.77–2.52), not HR 2.69 (95% CI 1.77–4.07), and it is an umbrella review rather than the prospective study described in the citing sentence. (LLM, conf=0.90)
Experimental — accuracy not yet measuredBaseline MDD increases the risk of future cardiovascular events.
“Indeed, several meta-analyses of prospective cohort studies have reported that baseline MDD increases the risk of future cardiovascular events38-41.”
From Comorbidity between major depressive disorder and physical diseases: a comprehensive review of epidemiology, mechanisms and management (2023) · cites this paper as [41]
The Discussion reports that depressive disorders are associated with subsequent major cardiac events in patients who have had a myocardial infarction. That supports the direction of the claim, but the paper does not establish it specifically for baseline major depressive disorder or for future cardiovascular events across a general population; its reported finding concerns patients with existing cardiovascular disease. Page numbers are unavailable in our copy. (LLM, conf=0.84)
Experimental — accuracy not yet measured
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Mental Disorders Following Implantable Cardioverter-Defibrillator Therapy
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Self-citationSocioenvironmental determinants of polypharmacy in mental health disorders: a systematic review
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Prevalence of mental disorders and related risk factors in refugees and asylum seekers in Campania
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Two Long-Acting Antipsychotics in a Patient with Treatment-Resistant Schizophrenia: A Case Report
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Schizophrenia and Other Late-Life Psychoses
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Population-level prevention of severe mental disorders
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Psychometric and Factor Analysis of the Greek Version of the SpREUK Questionnaire
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Schizophrenia and Other Late-Life Psychoses
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- Authors
- Dragioti, E., Radua, J., Solmi, M., Gosling, C. J., Oliver, D., Lascialfari, F., Ahmed, M., Cortese, S., Estradé, A., Arrondo, G., Gouva, M., Fornaro, M., Batiridou, A., Dimou, K., Tsartsalis, D., Carvalho, A. F., Shin, J. I., Berk, M., Stringhini, S., Correll, C. U., & Fusar‐Poli, P.
- Affiliations
- Linköping University (SE)
- Early Psychosis: Interventions and Clinical‐detection (EPIC) Lab, Department of Psychosis Studies Institute of Psychiatry, Psychology & Neuroscience, King's College London London UK
- University of Ottawa (CA)
- Université Paris Cité (FR)
- King's College London (GB)
- University of Pavia (IT)
- University of Nottingham (GB)
- University of Southampton (GB)
- University of Ioannina (GR)
- Federico II University Hospital (IT)
- Hippocration General Hospital (GR)
- Barwon Health (AU)
- Yonsei University (KR)
- University of Geneva (CH)
- Northwell Health (US)
- ORCID
- Venue
- World Psychiatry
- Publisher
- Wiley
- Published
- 2023-01-14
- Volume
- 22
- Issue
- 1
- Pages
- 86-104
- ISSN
- 1723-8617 (ISSN-L)
- 2051-5545
- PMC
- PMC9840513
- OpenAlex
- W4316174572
- Cited by
- 130
- References
- 179
- Citations by year
- 2026: 31 · 2025: 39 · 2024: 45 · 2023: 15
- FWCI
- 38.48
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- World Psychiatry (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- ePrints Soton (University of Southampton) (acceptedVersion)
- Research Portal (King's College London) (submittedVersion, other-oa)
- HAL (submittedVersion)
- Figshare (submittedVersion, cc-by)
- IRIS (submittedVersion)
- SERVAL (Université de Lausanne) (submittedVersion)
- Funders
- Medical Research Council
- National Health and Medical Research Council (2017131, 1156072)
- Agencia Estatal de Investigación (AEI//10.13039/501100011033/, 501100011033, 10.13039/501100011033, 13039, .13039/501100011033, 10.13039, AEI/10)
- European Social Fund (501100011033, AEI/10.13039/501100011033)
- Topics
- Social Sciences › Psychology › Social Psychology › Mental Health Treatment and Access
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Health and Mental Health
- Health Sciences › Medicine › Epidemiology › Chronic Disease Management Strategies
- Keywords
- mental illness, physical illness, bidirectional relationship, population attributable fraction, all-cause mortality, disease-specific mortality, depressive disorders, schizophrenia, heart failure, cardiovascular disease, diabetes mellitus, chronic kidney disease, chronic obstructive pulmonary disease, quality of life, disability, symptom severity, treatment outcomes, cardiovascular mortality, cancer mortality
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