Evidence-based atlas of risk and protective factors for psychotic disorders: an umbrella review to inform personalized prognosis and prevention.

Identifying updated, evidence-based risk and protective factors for psychotic disorders is essential to advancing scientific and clinical knowledge of their etiology. Since the most recent umbrella review published in this journal, the evidence base has expanded substantially. Following a pre-registered protocol, we searched the Web of Science for systematic reviews with meta-analyses of observational studies published between the search date of the last umbrella review (February 1, 2017) and March 31, 2025, examining associations of sociodemographic, parental, perinatal, and later factors or antecedents with ICD/DSM (any version) diagnoses of non-organic psychotic disorders. We graded associations between each putative factor and psychotic disorders using standardized international classification criteria: convincing (class I), highly suggestive (class II), suggestive (class III), and weak (class IV). We also conducted sensitivity analyses: a) lowering the classification criterion requiring more than 1,000 cases to 500 cases, b) restricted to prospective studies (class I-II factors), and c) testing more robust estimates of uncertainty (Hartung-Knapp-Sidik-Jonkman method). Then, we estimated the population attributable fraction (PAF) for potentially modifiable class I-III factors. Study quality was assessed with A MeaSurement Tool to Assess systematic Reviews (AMSTAR). A total of 69 systematic reviews and meta-analyses were included, reporting on 970 individual studies and 221 risk or protective factors for psychotic disorders. Six risk factors showed convincing (class I) evidence of association: Black-African ethnicity in England (odds ratio, OR=4.89, 95% CI: 4.04-5.92), South Asian ethnicity in England (OR=2.15, 95% CI: 1.69-2.73), paternal age <20 years (OR=1.34, 95% CI: 1.20-1.50), birthweight under 2,000 g (OR=1.77, 95% CI: 1.48-2.13), birthweight under 2,500 g (OR=1.50, 95% CI: 1.38-1.64), and maternal history of three or more previous pregnancies (OR=1.32, 95% CI: 1.20-1.45). Eighteen additional factors were highly suggestive (class II): maternal psychosis, Black-Caribbean ethnicity in England, any maternal mental health disorder, ethnic minority status in a low ethnic density area, first-generation immigrant status, cannabis use 5 to 7 days per week, Toxoplasma gondii IgG positivity, history of attention-deficit/hyperactivity disorder (ADHD), trait anhedonia, olfactory identification ability, premorbid IQ, and seven factors pertaining to minor physical anomalies. Two additional factors were upgraded from class IV to class II in our sensitivity analyses: clinical high-risk for psychosis (CHR-P) state, and soft neurological signs. Twenty-six factors (including four protective factors) were suggestive (class III), 75 were weak (class IV), and 96 were non-significant. Sensitivity analyses restricted to prospective studies downgraded some of the above factors, but only total minor physical anomalies became non-significant. The largest PAFs (>10%) were found for childhood adversities (40.69%), Toxoplasma gondii IgG positivity (20.47%), cannabis use 5-7 days per week (12.75%), and CHR-P state (12.68%). The sensitivity analyses employing robust uncertainty estimates confirmed that, among class I factors, Black-African ethnicity in England, birthweight under 2,000 g, and birthweight under 2,500 g retained their level of evidence. The mean AMSTAR score was 7.73 (SD=2.09). These findings provide an evidence-based, updated atlas of risk and protective factors for psychosis, advancing epidemiological knowledge, refining precision psychiatry, identifying targets for preventive intervention, and guiding global public health research.

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PubMed
Published
2026-10-01
DOI
https://doi.org/10.1002/wps.70093
Primary Topic
Schizophrenia research and treatment
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article
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article

Evidence-based atlas of risk and protective factors for psychotic disorders: an umbrella review to inform personalized prognosis and prevention.

Oliver Howes, Celso Arango, Crick Lund, Giovanni de Girolamo et al.
PubMed
Schizophrenia research and treatment
article

Evidence-based atlas of risk and protective factors for psychotic disorders: an umbrella review to inform personalized prognosis and prevention.

Oliver Howes, Celso Arango, Crick Lund, Giovanni de Girolamo, Samuele Cortese, Samuele Cortese, Sameer Jauhar, RUDOLF UHER, Dong Keon Yon, Robin M. Murray, A. Catalan, Joaquim Raduà, Merete Nordentoft, Cathy Davies, Gonzalo Salazar de Pablo, Cathy Davies, Luigi Giuseppe Grassi, Dominic Oliver, Laura Fusar‐Poli, Clàudia Aymerich, Christoph Ulrich Correll, Paolo Fusar‐Poli, Stefano Damiani, Borja Pedruzo, Eduard Vieta, Antonio Melillo, Matteo Tonna, Alessio Maria Monteleone, Simon Červenka, Michele De Prisco, James Hunter MacCabe, Marco Solmi, Matteo Tonna, Ricardo Twumasi, Gonzalo Salazar de Pablo, Laura Fusar‐Poli, Thomas A. Pollak, Stefano Damiani, Luis Alameda, Christoph U. Correll, Michele De Prisco, Merete Nordentoft, Simon Cervenka, Manuel Capra, Dong Keon Yon, Celso Arango, Alessio Maria Monteleone, Paolo Fusar-Poli, Marco Solmi, Joaquim Radua, Ana Catalan, Ilaria Stirpe, Giovanni de Girolamo, Luigi Grassi, Eduard Vieta, Ricardo Twumasi, Thomas A. Pollak, Oliver Howes, Kelly Diederen, Robin M. Murray
article en

Abstract

Identifying updated, evidence-based risk and protective factors for psychotic disorders is essential to advancing scientific and clinical knowledge of their etiology. Since the most recent umbrella review published in this journal, the evidence base has expanded substantially. Following a pre-registered protocol, we searched the Web of Science for systematic reviews with meta-analyses of observational studies published between the search date of the last umbrella review (February 1, 2017) and March 31, 2025, examining associations of sociodemographic, parental, perinatal, and later factors or antecedents with ICD/DSM (any version) diagnoses of non-organic psychotic disorders. We graded associations between each putative factor and psychotic disorders using standardized international classification criteria: convincing (class I), highly suggestive (class II), suggestive (class III), and weak (class IV). We also conducted sensitivity analyses: a) lowering the classification criterion requiring more than 1,000 cases to 500 cases, b) restricted to prospective studies (class I-II factors), and c) testing more robust estimates of uncertainty (Hartung-Knapp-Sidik-Jonkman method). Then, we estimated the population attributable fraction (PAF) for potentially modifiable class I-III factors. Study quality was assessed with A MeaSurement Tool to Assess systematic Reviews (AMSTAR). A total of 69 systematic reviews and meta-analyses were included, reporting on 970 individual studies and 221 risk or protective factors for psychotic disorders. Six risk factors showed convincing (class I) evidence of association: Black-African ethnicity in England (odds ratio, OR=4.89, 95% CI: 4.04-5.92), South Asian ethnicity in England (OR=2.15, 95% CI: 1.69-2.73), paternal age <20 years (OR=1.34, 95% CI: 1.20-1.50), birthweight under 2,000 g (OR=1.77, 95% CI: 1.48-2.13), birthweight under 2,500 g (OR=1.50, 95% CI: 1.38-1.64), and maternal history of three or more previous pregnancies (OR=1.32, 95% CI: 1.20-1.45). Eighteen additional factors were highly suggestive (class II): maternal psychosis, Black-Caribbean ethnicity in England, any maternal mental health disorder, ethnic minority status in a low ethnic density area, first-generation immigrant status, cannabis use 5 to 7 days per week, Toxoplasma gondii IgG positivity, history of attention-deficit/hyperactivity disorder (ADHD), trait anhedonia, olfactory identification ability, premorbid IQ, and seven factors pertaining to minor physical anomalies. Two additional factors were upgraded from class IV to class II in our sensitivity analyses: clinical high-risk for psychosis (CHR-P) state, and soft neurological signs. Twenty-six factors (including four protective factors) were suggestive (class III), 75 were weak (class IV), and 96 were non-significant. Sensitivity analyses restricted to prospective studies downgraded some of the above factors, but only total minor physical anomalies became non-significant. The largest PAFs (>10%) were found for childhood adversities (40.69%), Toxoplasma gondii IgG positivity (20.47%), cannabis use 5-7 days per week (12.75%), and CHR-P state (12.68%). The sensitivity analyses employing robust uncertainty estimates confirmed that, among class I factors, Black-African ethnicity in England, birthweight under 2,000 g, and birthweight under 2,500 g retained their level of evidence. The mean AMSTAR score was 7.73 (SD=2.09). These findings provide an evidence-based, updated atlas of risk and protective factors for psychosis, advancing epidemiological knowledge, refining precision psychiatry, identifying targets for preventive intervention, and guiding global public health research.

PubMedVol. 25(3)
Uppsala University (SE), University of Copenhagen (DK), University of Parma (IT), National Health Service (GB), Dalhousie University (CA), Northwell Health (US), Feinstein Institute for Medical Research (US), Hofstra University (US), University of Ottawa (CA), University of Cape Town (ZA), University of the Basque Country (ES), King's College London (GB), University of Campania "Luigi Vanvitelli" (IT), South London and Maudsley NHS Foundation Trust (GB), University of Ferrara (IT), University of Pavia (IT), Hospital Universitario La Paz (ES), Ottawa Hospital (CA), Mental Health Services (DK), Instituto de Salud Carlos III (ES), Stockholm County Council (SE), Oxford Health NHS Foundation Trust (GB), Centre Hospitalier Universitaire Vaudois (CH), Copenhagen University Hospital (DK), Karolinska Institutet (SE), Hospital General Universitario Gregorio Marañón (ES), Kyung Hee University (KR), University of Oxford (GB), NYU Langone Health (US), Centro de Investigación Biomédica en Red de Salud Mental (ES), Istituti Clinici Scientifici Maugeri (IT), Hospital de Basurto (ES), Donald & Barbara Zucker School of Medicine at Hofstra/Northwell (US), Kyung Hee University Medical Center (KR), Centro San Giovanni di Dio Fatebenefratelli (IT), Hospital Clínic de Barcelona (ES), Azienda Unita' Sanitaria Locale di Parma (IT), Osakidetza (ES), Stockholm Health Care Services (SE), Hospital Universitario Virgen del Rocío (ES), Consorci Institut D'Investigacions Biomediques August Pi I Sunyer (ES), Zucker Hillside Hospital (US), University of Southampton (GB), Ottawa Hospital Research Institute (CA), Deutsches Zentrum für Psychische Gesundheit (DE), Alan J Flisher Centre for Public Mental Health (ZA), Imperial College London (GB), University of Bari Aldo Moro (IT), New York University (US), Universidad Autónoma de Madrid (ES), Universitat de Barcelona (ES), Charité - Universitätsmedizin Berlin (DE), Universidad de Sevilla (ES), University of Birmingham (GB), Ludwig-Maximilians-Universität München (DE)
Fundación Alicia Koplowitz, University of Ottawa, National Institute for Health and Care Research, European Commission, Ministerio de Ciencia e Innovación, Centro de Investigación Biomédica en Red de Salud Mental, National Institutes of Health, Horizon 2020 Framework Programme, Instituto de Salud Carlos III
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Schizophrenia research and treatment
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