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What causes psychosis? An umbrella review of risk and protective factors
Open accessAbstract
Psychosis is a heterogeneous psychiatric condition for which a multitude of risk and protective factors have been suggested. This umbrella review aimed to classify the strength of evidence for the associations between each factor and psychotic disorders whilst controlling for several biases. The Web of Knowledge database was searched to identify systematic reviews and meta‐analyses of observational studies which examined associations between socio‐demographic, parental, perinatal, later factors or antecedents and psychotic disorders, and which included a comparison group of healthy controls, published from 1965 to January 31, 2017. The literature search and data extraction followed PRISMA and MOOSE guidelines. The association between each factor and ICD or DSM diagnoses of non‐organic psychotic disorders was graded into convincing, highly suggestive, suggestive, weak, or non‐significant according to a standardized classification based on: number of psychotic cases, random‐effects p value, largest study 95% confidence interval, heterogeneity between studies, 95% prediction interval, small study effect, and excess significance bias. In order to assess evidence for temporality of association, we also conducted sensitivity analyses restricted to data from prospective studies. Fifty‐five meta‐analyses or systematic reviews were included in the umbrella review, corresponding to 683 individual studies and 170 putative risk or protective factors for psychotic disorders. Only the ultra‐high‐risk state for psychosis (odds ratio, OR=9.32, 95% CI: 4.91‐17.72) and Black‐Caribbean ethnicity in England (OR=4.87, 95% CI: 3.96‐6.00) showed convincing evidence of association. Six factors were highly suggestive (ethnic minority in low ethnic density area, second generation immigrants, trait anhedonia, premorbid IQ, minor physical anomalies, and olfactory identification ability), and nine were suggestive (urbanicity, ethnic minority in high ethnic density area, first generation immigrants, North‐African immigrants in Europe, winter/spring season of birth in Northern hemisphere, childhood social withdrawal, childhood trauma, Toxoplasma gondii IgG, and non‐right handedness). When only prospective studies were considered, the evidence was convincing for ultra‐high‐risk state and suggestive for urbanicity only. In summary, this umbrella review found several factors to be associated with psychotic disorders with different levels of evidence. These risk or protective factors represent a starting point for further etiopathological research and for the improvement of the prediction of psychosis.
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“The CHR-P criteria are robustly associated with psychosis onset (Odds Ratio, OR=9.32) 44 within high-risk clinical samples (but not in the general population 84 )”
From Preventive psychiatry: a blueprint for improving the mental health of young people (2021) · cites this paper as [44]
In the citing paper
“Transition to psychosis is associated with clinically meaningful real-world outcomes 89 and is modulated by baseline levels of attenuated positive psychotic (OR=2.56) and negative (OR=2.68) symptoms, while good functioning reduces the risk (OR=0.59) 44 .”
From Preventive psychiatry: a blueprint for improving the mental health of young people (2021) · cites this paper as [44]
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“Psychotic disorders are infrequent before the age of 14 43 ; their risk peaks in the age group of 15-35 and declines after the age of 35 44 .”
From Preventive psychiatry: a blueprint for improving the mental health of young people (2021) · cites this paper as [44]
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“Black - Caribbean ethnicity in England (OR=4.87) 44 ****”
From Preventive psychiatry: a blueprint for improving the mental health of young people (2021) · cites this paper as [44]
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Age at onset of mental disorders worldwide: Large-scale meta-analysis of 192 epidemiological studies
Solmi, M., Radua, J., Olivola, M., Croce, E., Soardo, L., Salazar de Pablo, G., Il Shin, J., Kirkbride, J. B., Jones, P., Kim, J. H., et al. (2022) · Molecular Psychiatry · doi:10.1038/s41380-021-01161-7 · Cited by 3,835
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Metadata
- Authors
- Radua, J., Ramella‐Cravaro, V., Ioannidis, J. P. A., Reichenberg, A., Phiphopthatsanee, N., Amir, T., Yenn Thoo, H., Oliver, D., Davies, C., Morgan, C., McGuire, P., Murray, R. M., & Fusar‐Poli, P.
- Affiliations
- Early Psychosis: Interventions & Clinical‐detection (EPIC) Lab, Department of Psychosis Studies Institute of Psychiatry, Psychology & Neuroscience, King's College London London UK
- King's College London (GB)
- Stanford Medicine (US)
- ORCID
- Venue
- World Psychiatry
- Publisher
- Wiley
- Published
- 2018-01-19
- Volume
- 17
- Issue
- 1
- Pages
- 49-66
- ISSN
- 1723-8617 (ISSN-L)
- 2051-5545
- PMC
- PMC5775150
- OpenAlex
- W2768338105
- Cited by
- 553
- References
- 158
- Citations by year
- 2026: 33 · 2025: 55 · 2024: 67 · 2023: 70 · 2022: 73 · 2021: 92 · 2020: 82 · 2019: 66 · 2018: 15
- FWCI
- 49.82
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- World Psychiatry (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion, other-oa)
- Funders
- Medical Research Council
- Instituto de Salud Carlos III (CP14/00041 and PI14/00292)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Social Sciences › Psychology › Clinical Psychology › Psychopathy, Forensic Psychiatry, Sexual Offending
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Maternal Mental Health During Pregnancy and Postpartum
- Keywords
- psychosis, risk factors, protective factors, ethnic minorities, urbanicity, immigrant status, childhood trauma, season of birth, Toxoplasma gondii, handedness, anhedonia, premorbid intelligence, birth order
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