What causes psychosis? An umbrella review of risk and protective factors
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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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CHR-P criteria are robustly associated with psychosis onset (OR=9.32) within high-risk clinical samples, but not in the general population.
“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]
Transition to psychosis is associated with baseline levels of attenuated positive psychotic symptoms (OR=2.56) and negative symptoms (OR=2.68), while good functioning reduces the risk (OR=0.59).
“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]
Psychotic disorders are infrequent before the age of 14; their risk peaks in the age group of 15-35 and declines after the age of 35.
“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]
Black-Caribbean ethnicity in England is associated with psychotic disorders (OR=4.87).
“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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The Science of Prognosis in Psychiatry: A Review
Fusar-Poli, P., Hijazi, Z., Stahl, D., & Steyerberg, E. W. (2018) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2018.2530 · Cited by 197 · see citing works
Self-citationClimate change, environment pollution, COVID-19 pandemic and mental health
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Gülöksüz, S., Pries, L.-K., Delespaul, P., Kenis, G., Luykx, J. J., Lin, B. D., Richards, A. L., Akdede, B. B., Binbay, T., Altınyazar, V., et al. (2019) · World Psychiatry · doi:10.1002/wps.20629 · Cited by 189 · see citing works
Self-citationThe schizophrenia syndrome, circa 2024: What we know and how that informs its nature
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Self-citationPsychological trauma as a transdiagnostic risk factor for mental disorder: an umbrella meta-analysis
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Self-citationOliver, D., Reilly, T. J., Boy, O. B., Petros, N., Davies, C., Borgwardt, S., McGuire, P. K., & Fusar‐Poli, P. (2019) · Schizophrenia Bulletin · doi:10.1093/schbul/sbz039 · Cited by 164 · see citing works
Self-citationGastaldon, C., Solmi, M., Correll, C. U., Barbui, C., & Schoretsanitis, G. (2022) · The British Journal of Psychiatry · doi:10.1192/bjp.2021.222 · Cited by 152 · see citing works
Risk factors for eating disorders: an umbrella review of published meta-analyses
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Self-citationMigration, ethnicity and psychoses: evidence, models and future directions
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Self-citationRaduà, J., Prisco, M. D., Oliva, V., Fico, G., Vieta, E., & Fusar-Poli, P. (2024) · World Psychiatry · doi:10.1002/wps.21219 · Cited by 132 · see citing works
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Self-citationCurrent findings and perspectives on aberrant neural oscillations in schizophrenia
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Jester, D. J., Thomas, M. L., Sturm, E. T., Harvey, P. D., Keshavan, M. S., Davis, B. J., Saxena, S., Tampi, R. R., Leutwyler, H. C., Compton, M. T., et al. (2023) · Schizophrenia Bulletin · doi:10.1093/schbul/sbad023 · Cited by 121 · see citing works
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Self-citationDragioti, E., Raduà, J., Solmi, M., Arango, C., Oliver, D., Cortese, S., Jones, P. B., Shin, J. I., Correll, C. U., & Fusar‐Poli, P. (2022) · Molecular Psychiatry · doi:10.1038/s41380-022-01586-8 · Cited by 114 · see citing works
Self-citationPreventive Treatments for Psychosis: Umbrella Review (Just the Evidence)
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Self-citationSalazar de Pablo, G., Catalan, A., & Fusar-Poli, P. (2020) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2019.3561 · Cited by 103 · see citing works
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Self-citationMongan, D., Föcking, M., Healy, C., Susai, S. R., Heurich, M., Wynne, K. J., Nelson, B., McGorry, P. D., Amminger, G. P., Nordentoft, M., et al. (2020) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2020.2459 · Cited by 102 · see citing works
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The association between neonatal vitamin D status and risk of schizophrenia
Eyles, D. W., Trzaskowski, M., Vinkhuyzen, A. A. E., Mattheisen, M., Meier, S. M., Gooch, H. M., Anggono, V., Cui, X., Tan, M. C., Burne, T. H. J., et al. (2018) · Scientific Reports · doi:10.1038/s41598-018-35418-z · Cited by 103 · see citing works
Cost-effectiveness of early intervention in psychosis: systematic review
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Fusar-Poli, P., Werbeloff, N., Rutigliano, G., Oliver, D., Davies, C., Stahl, D., McGuire, P., & Osborn, D. (2019) · Schizophrenia Bulletin · doi:10.1093/schbul/sby070 · Cited by 95 · see citing works
Self-citationHunter, A., Murray, R., Asher, L., & Leonardi-Bee, J. (2020) · Nicotine & Tobacco Research · doi:10.1093/ntr/nty160 · Cited by 95 · see citing works
Self-citationImpaired neural replay of inferred relationships in schizophrenia
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Schizophrenia: The new etiological synthesis
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Irving, J., Patel, R., Oliver, D., Colling, C., Pritchard, M., Broadbent, M., Baldwin, H., Stahl, D., Stewart, R., & Fusar-Poli, P. (2021) · Schizophrenia Bulletin · doi:10.1093/schbul/sbaa126 · Cited by 92 · see citing works
Self-citationFusar-Poli, P., Sullivan, S. A., Shah, J. L., & Uhlhaas, P. J. (2019) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2019.00774 · Cited by 92 · see citing works
Self-citationKotlicka‐Antczak, M., Podgórski, M. T., Oliver, D., Marić, N. P., Valmaggia, L., & Fusar‐Poli, P. (2020) · Early Intervention in Psychiatry · doi:10.1111/eip.12950 · Cited by 92 · see citing works
Self-citationBardol, O., Grot, S., Oh, H. Y., Poulet, E., Zeroug-Vial, H., Brunelin, J., & Leaune, É. (2020) · Psychological Medicine · doi:10.1017/s003329172000094x · Cited by 92 · see citing works
Interventions for reducing loneliness: An umbrella review of intervention studies
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Efficacy of psychosocial interventions for Autism spectrum disorder: an umbrella review
Gosling, C. J., Cartigny, A., Mellier, B. C., Solanes, A., Raduà, J., & Delorme, R. (2022) · Molecular Psychiatry · doi:10.1038/s41380-022-01670-z · Cited by 88 · see citing works
de Pablo, G. S., Soardo, L., Cabras, A., Pereira, J., Kaur, S., Besana, F., Arienti, V., Coronelli, F., Shin, J. I., Solmi, M., et al. (2022) · Epidemiology and Psychiatric Sciences · doi:10.1017/s2045796021000639 · Cited by 85 · see citing works
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Self-citation‘At risk mental state’ clinics for psychosis – an idea whose time has come – and gone!
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Self-citationEstablishing a clinical service to prevent psychosis: What, how and when? Systematic review
de Pablo, G. S., Estradé, A., Cutroni, M., Andlauer, O., & Fusar‐Poli, P. (2021) · Translational Psychiatry · doi:10.1038/s41398-020-01165-x · Cited by 83 · see citing works
Self-citationde Pablo, G. S., Woods, S. W., Drymonitou, G., Ruiz, H. D. D., & Fusar‐Poli, P. (2021) · Brain Sciences · doi:10.3390/brainsci11111544 · Cited by 80 · see citing works
Self-citationSolmi, M., Cortese, S., Vita, G., Prisco, M. D., Raduà, J., Dragioti, E., Köhler‐Forsberg, O., Madsen, N. M., Rohde, C., Eudave, L., et al. (2023) · Molecular Psychiatry · doi:10.1038/s41380-023-02298-3 · Cited by 84 · see citing works
Self-citationD’Agostino, A., D’Angelo, S., Giordano, B., Cigognini, A. C., Chirico, M., Redaelli, C., & Gambini, O. (2020) · Schizophrenia Bulletin · doi:10.1093/schbul/sbaa112 · Cited by 77 · see citing works
Leaune, É., Dealberto, M., Luck, D., Grot, S., Zeroug-Vial, H., Poulet, E., & Brunelin, J. (2018) · Psychological Medicine · doi:10.1017/s0033291718002271 · Cited by 58 · see citing works
COVID-19-associated psychosis: A systematic review of case reports
Smith, C. M., Gilbert, E. B., Riordan, P. A., Helmke, N., von Isenburg, M., Kincaid, B. R., & Shirey, K. (2021) · General Hospital Psychiatry · doi:10.1016/j.genhosppsych.2021.10.003 · Cited by 75 · see citing works
Factors Moderating the Association between Cannabis Use and Psychosis Risk: A Systematic Review
van der Steur, S. J., Batalla, A., & Bossong, M. G. (2020) · Brain Sciences · doi:10.3390/brainsci10020097 · Cited by 74 · see citing works
Schizophrenia: A Narrative Review of Etiopathogenetic, Diagnostic and Treatment Aspects
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Fullana, M. A., Tortella‐Feliu, M., de la Cruz, L. F., Chamorro, J., Pérez-Vigil, A., Ioannidis, J. P. A., Solanes, A., Guardiola-Ripoll, M., Almodóvar-Payá, C., Miranda‐Olivos, R., et al. (2019) · Psychological Medicine · doi:10.1017/s0033291719001247 · Cited by 71 · see citing works
Self-citationJahrami, H., AlKaabi, J., Trabelsi, K., Pandi-Perumal, S. R., Saif, Z., Seeman, M. V., & Vitiello, M. V. (2023) · Journal of Psychosomatic Research · doi:10.1016/j.jpsychores.2023.111479 · Cited by 72 · see citing works
O’Connor, K., Wrigley, M., Jennings, R., Hill, M. B., & Niazi, A. (2020) · Irish Journal of Psychological Medicine · doi:10.1017/ipm.2020.64 · Cited by 69 · see citing works
Oliver, D., Raduà, J., Reichenberg, A., Uher, R., & Fusar‐Poli, P. (2019) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2019.00174 · Cited by 69 · see citing works
Self-citationForced normalization: A systematic review
Calle‐López, Y., Ladino, L. D., Benjumea‐Cuartas, V., Castrillón‐Velilla, D. M., Téllez‐Zenteno, J. F., & Wolf, P. (2019) · Epilepsia · doi:10.1111/epi.16276 · Cited by 66 · see citing works
Yıldız, E. (2020) · Perspectives in Psychiatric Care · doi:10.1111/ppc.12396 · Cited by 67 · see citing works
Mentis, A. A., Dardiotis, E., Efthymiou, V., & Chrousos, G. P. (2021) · BMC Medicine · doi:10.1186/s12916-020-01873-7 · Cited by 65 · see citing works
Chemsex and Psychosis: A Systematic Review
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Pries, L.-K., Ferro, G. A. D., van Os, J., Delespaul, P., Kenis, G., Lin, B. D., Luykx, J. J., Richards, A. L., Akdede, B. B., Binbay, T., et al. (2020) · Epidemiology and Psychiatric Sciences · doi:10.1017/s2045796020000943 · Cited by 60 · see citing works
Self-citationFusar-Poli, P., Spencer, T., De Micheli, A., Curzi, V., Nandha, S., & McGuire, P. (2020) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2020.08.002 · Cited by 57 · see citing works
Self-citationRaket, L. L., Jaskolowski, J., Kinon, B. J., Brasen, J. C., Jönsson, L., Wehnert, A., & Fusar-Poli, P. (2020) · The Lancet Digital Health · doi:10.1016/s2589-7500(20)30024-8 · Cited by 60 · see citing works
Self-citationAre climate change and mental health correlated?
Ramadan, A., & Ataallah, A. G. (2021) · General Psychiatry · doi:10.1136/gpsych-2021-100648 · Cited by 68 · see citing works
Bariatric surgery and health outcomes: An umbrella analysis
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Schizophrenia is Associated With an Aberrant Immune Response to Epstein–Barr Virus
Dickerson, F., Jones‐Brando, L. V., Ford, G. M., Genovese, G., Stallings, C. R., Origoni, A. E., O’Dushlaine, C. T., Katsafanas, E., Sweeney, K., Khushalani, S., et al. (2018) · Schizophrenia Bulletin · doi:10.1093/schbul/sby164 · Cited by 59 · see citing works
Alvarez-Mon, M. A., Llavero-Valero, M., Sánchez-Bayona, R., Pereira-Sanchez, V., Vallejo-Valdivielso, M., Monserrat, J., Lahera, G., Asunsolo del Barco, A., & Alvarez-Mon, M. (2019) · Journal of Medical Internet Research · doi:10.2196/14110 · Cited by 52 · see citing works
Brokmeier, L. L., Firth, J., Vancampfort, D., Smith, L., Deenik, J., Rosenbaum, S., Stubbs, B., & Schuch, F. B. (2020) · Psychiatry Research · doi:10.1016/j.psychres.2019.112675 · Cited by 56 · see citing works
de Pablo, G. S., Besana, F., Arienti, V., Catalán, A., Vaquerizo‐Serrano, J., Cabras, A., Pereira, J. F., Soardo, L., Coronelli, F., Kaur, S., et al. (2021) · EClinicalMedicine · doi:10.1016/j.eclinm.2021.100909 · Cited by 57 · see citing works
Self-citationProgression from being at-risk to psychosis: next steps
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Travica, N., Lotfaliany, M., Marriott, A., Safavynia, S. A., Lane, M. M., Gray, L. J., Veronese, N., Berk, M., Skvarc, D., Aslam, H., et al. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm12041610 · Cited by 54 · see citing works
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Self-citationDiagnosis, prognosis, and treatment of brief psychotic episodes: a review and research agenda
Fusar‐Poli, P., de Pablo, G. S., Rajkumar, R. P., López‐Díaz, Á., Malhotra, S., Heckers, S., Lawrie, S. M., & Pillmann, F. (2021) · The Lancet Psychiatry · doi:10.1016/s2215-0366(21)00121-8 · Cited by 52 · see citing works
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Hypofunctional Dopamine Uptake and Antipsychotic Treatment-Resistant Schizophrenia
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Self-citationNeed for Ethnic and Population Diversity in Psychosis Research
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- 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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