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World Psychiatry. 2018 Feb;17(1):49-66. doi: 10.1002/wps.20490.

What causes psychosis? An umbrella review of risk and protective factors.

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Early Psychosis: Interventions & Clinical-detection (EPIC) Lab, Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
FIDMAG Germanes Hospitalàries, CIBERSAM, Sant Boi de Llobregat, Spain.
Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden.
Department of Neurosciences, Psychology, Drug Research and Child Health, University of Florence, Florence, Italy.
Department of Medicine, Stanford Prevention Research Center, Stanford, CA, USA.
Department of Health Research and Policy, Stanford University School of Medicine, Stanford, CA, USA.
Meta-Research Innovation Center at Stanford, Stanford University, Stanford, CA, USA.
Department of Statistics, Stanford University School of Humanities and Sciences, Stanford, CA, USA.
Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Department of Preventive Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Frieman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
National Institute for Health Research (NIHR) Maudsley Biomedical Research Center, London, UK.
OASIS Service, South London and Maudsley NHS Foundation Trust, London, UK.


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.


Black-Caribbean ethnicity; Schizophrenia; antecedents; environment; parental factors; perinatal factors; psychosis; risk; socio-demographic factors; ultra-high-risk state for psychosis; urbanicity

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