Global population attributable fraction of potentially modifiable risk factors for mental disorders: a meta-umbrella systematic review

Elena Dragioti, Joaquim Radua, Marco Solmi, Celso Arango, Dominic Oliver, Samuele Cortese, Peter B. Jones, Jae Il Shin, Christoph U. Correll, Paolo Fusar-Poli

Research output: Contribution to journalArticlepeer-review


Numerous risk factors for mental disorders have been identified. However, we do not know how many disorders we could prevent and to what extent by modifying these risk factors. This study quantifies the Population Attributable Fraction (PAF) of potentially modifiable risk factors for mental disorders. We conducted a PRISMA 2020-compliant (Protocol: meta-umbrella systematic review (Web of Science/PubMed/Cochrane Central Register of Reviews/Ovid/PsycINFO, until 05/12/2021) of umbrella reviews reporting associations between potentially modifiable risk factors and ICD/DSM mental disorders, restricted to highly convincing (class I) and convincing (class II) evidence from prospective cohorts. The primary outcome was the global meta-analytical PAF, complemented by sensitivity analyses across different settings, the meta-analytical Generalised Impact Fraction (GIF), and study quality assessment (AMSTAR). Seven umbrella reviews (including 295 meta-analyses and 547 associations) identified 28 class I–II risk associations (23 risk factors; AMSTAR: 45.0% high-, 35.0% medium-, 20.0% low quality). The largest global PAFs not confounded by indication were 37.84% (95% CI = 26.77–48.40%) for childhood adversities and schizophrenia spectrum disorders, 24.76% (95% CI = 13.98–36.49%) for tobacco smoking and opioid use disorders, 17.88% (95% CI = not available) for job strain and depression, 14.60% (95% CI = 9.46–20.52%) for insufficient physical activity and Alzheimer’s disease, 13.40% (95% CI = 7.75–20.15%) for childhood sexual abuse and depressive disorders, 12.37% (95% CI = 5.37–25.34%) for clinical high-risk state for psychosis and any non-organic psychotic disorders, 10.00% (95% CI = 5.62–15.95%) for three metabolic factors and depression, 9.73% (95% CI = 4.50–17.30%) for cannabis use and schizophrenia spectrum disorders, and 9.30% (95% CI = 7.36–11.38%) for maternal pre-pregnancy obesity and ADHD. The GIFs confirmed the preventive capacity for these factors. Addressing several potentially modifiable risk factors, particularly childhood adversities, can reduce the global population-level incidence of mental disorders.

Original languageEnglish
JournalMolecular Psychiatry
Publication statusAccepted/In press - 2022

Bibliographical note

Funding Information:
The study was funded by a Wellcome Trust grant to Paolo Fusar-Poli (Early DetectioN of menTal disorERs, ENTER: 215793/Z/19/Z). Dr Arango receives support from the Spanish Ministry of Science and Innovation. Instituto de Salud Carlos III (SAM16PE07CP1, PI16/02012, PI19/024), co-financed by ERDF Funds from the European Commission, “A way of making Europe”, CIBERSAM. Madrid Regional Government (B2017/BMD-3740 AGES-CM-2), European Union Structural Funds. European Union Seventh Framework Program under grant agreements FP7-4-HEALTH-2009-2.2.1-2-241909 (Project EU-GEI), FP7- HEALTH-2013-2.2.1-2-603196 (Project PSYSCAN) and FP7- HEALTH-2013-2.2.1-2-602478 (Project METSY); and European Union H2020 Program under the Innovative Medicines Initiative 2 Joint Undertaking (grant agreement No 115916, Project PRISM, and grant agreement No 777394, Project AIMS-2-TRIALS), Fundación Familia Alonso and Fundación Alicia Koplowitz.

Funding Information:
No association was supported by class I evidence (Table ). Only one class II association involved tobacco smoking as a risk factor for opioid use disorder (RR = 2.61, 95% CI = 1.79–3.79).

Publisher Copyright:
© 2022, The Author(s).

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience


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