L Belbasis1, C A Köhler2, N Stefanis3, B Stubbs4,5, J van Os6,7, E Vieta8, M V Seeman9, C Arango10, A F Carvalho11,12, E Evangelou1,13. 1. Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, Greece. 2. Translational Psychiatry Research Group, Department of Clinical Medicine, Federal University of Ceará Medical School, Fortaleza, Brazil. 3. Department of Psychiatry, Eginition Hospital, National and Kapodistrian University of Athens Medical School, Athens, Greece. 4. Department of Physiotherapy, South London and Maudsley NHS Foundation Trust, London, UK. 5. Department of Health Service and Population Research, Institute of Psychiatry, King's College London, London, UK. 6. Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Centre Utrecht, Utrecht, The Netherlands. 7. Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, UK. 8. Bipolar Disorder Unit, Institute of Neuroscience, University of Barcelona, IDIBAPS and CIBERSAM, Barcelona, Spain. 9. Institute of Medical Science, University of Toronto, Toronto, ON, Canada. 10. Department of Child and Adolescent Psychiatry, University Hospital Gregorio Marañón, Complutense University of Madrid Medical School, CIBERSAM, Madrid, Spain. 11. Department of Psychiatry, University of Toronto, Toronto, ON, Canada. 12. Centre for Addiction & Mental Health (CAMH), Toronto, ON, Canada. 13. Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.
Abstract
OBJECTIVE: This study aimed to systematically appraise the meta-analyses of observational studies on risk factors and peripheral biomarkers for schizophrenia spectrum disorders. METHODS: We conducted an umbrella review to capture all meta-analyses and Mendelian randomization studies that examined associations between non-genetic risk factors and schizophrenia spectrum disorders. For each eligible meta-analysis, we estimated the summary effect size estimate, its 95% confidence and prediction intervals and the I2 metric. Additionally, evidence for small-study effects and excess significance bias was assessed. RESULTS: Overall, we found 41 eligible papers including 98 associations. Sixty-two associations had a nominally significant (P-value <0.05) effect. Seventy-two of the associations exhibited large or very large between-study heterogeneity, while 13 associations had evidence for small-study effects. Excess significance bias was found in 18 associations. Only five factors (childhood adversities, cannabis use, history of obstetric complications, stressful events during adulthood, and serum folate level) showed robust evidence. CONCLUSION: Despite identifying 98 associations, there is only robust evidence to suggest that cannabis use, exposure to stressful events during childhood and adulthood, history of obstetric complications, and low serum folate level confer a higher risk for developing schizophrenia spectrum disorders. The evidence on peripheral biomarkers for schizophrenia spectrum disorders remains limited.
OBJECTIVE: This study aimed to systematically appraise the meta-analyses of observational studies on risk factors and peripheral biomarkers for schizophrenia spectrum disorders. METHODS: We conducted an umbrella review to capture all meta-analyses and Mendelian randomization studies that examined associations between non-genetic risk factors and schizophrenia spectrum disorders. For each eligible meta-analysis, we estimated the summary effect size estimate, its 95% confidence and prediction intervals and the I2 metric. Additionally, evidence for small-study effects and excess significance bias was assessed. RESULTS: Overall, we found 41 eligible papers including 98 associations. Sixty-two associations had a nominally significant (P-value <0.05) effect. Seventy-two of the associations exhibited large or very large between-study heterogeneity, while 13 associations had evidence for small-study effects. Excess significance bias was found in 18 associations. Only five factors (childhood adversities, cannabis use, history of obstetric complications, stressful events during adulthood, and serum folate level) showed robust evidence. CONCLUSION: Despite identifying 98 associations, there is only robust evidence to suggest that cannabis use, exposure to stressful events during childhood and adulthood, history of obstetric complications, and low serum folate level confer a higher risk for developing schizophrenia spectrum disorders. The evidence on peripheral biomarkers for schizophrenia spectrum disorders remains limited.
Authors: Mario Maj; Jim van Os; Marc De Hert; Wolfgang Gaebel; Silvana Galderisi; Michael F Green; Sinan Guloksuz; Philip D Harvey; Peter B Jones; Dolores Malaspina; Patrick McGorry; Jouko Miettunen; Robin M Murray; Keith H Nuechterlein; Victor Peralta; Graham Thornicroft; Ruud van Winkel; Joseph Ventura Journal: World Psychiatry Date: 2021-02 Impact factor: 49.548
Authors: Sinan Guloksuz; Lotta-Katrin Pries; Philippe Delespaul; Gunter Kenis; Jurjen J Luykx; Bochao D Lin; Alexander L Richards; Berna Akdede; Tolga Binbay; Vesile Altınyazar; Berna Yalınçetin; Güvem Gümüş-Akay; Burçin Cihan; Haldun Soygür; Halis Ulaş; EylemŞahin Cankurtaran; Semra Ulusoy Kaymak; Marina M Mihaljevic; Sanja Andric Petrovic; Tijana Mirjanic; Miguel Bernardo; Bibiana Cabrera; Julio Bobes; Pilar A Saiz; María Paz García-Portilla; Julio Sanjuan; Eduardo J Aguilar; José Luis Santos; Estela Jiménez-López; Manuel Arrojo; Angel Carracedo; Gonzalo López; Javier González-Peñas; Mara Parellada; Nadja P Maric; Cem Atbaşog Lu; Alp Ucok; Köksal Alptekin; Meram Can Saka; Celso Arango; Michael O'Donovan; Bart P F Rutten; Jim van Os Journal: World Psychiatry Date: 2019-06 Impact factor: 49.548
Authors: Joseph Firth; Scott B Teasdale; Kelly Allott; Dan Siskind; Wolfgang Marx; Jack Cotter; Nicola Veronese; Felipe Schuch; Lee Smith; Marco Solmi; André F Carvalho; Davy Vancampfort; Michael Berk; Brendon Stubbs; Jerome Sarris Journal: World Psychiatry Date: 2019-10 Impact factor: 49.548
Authors: Lotta-Katrin Pries; Jim van Os; Margreet Ten Have; Ron de Graaf; Saskia van Dorsselaer; Maarten Bak; Bochao D Lin; Kristel R van Eijk; Gunter Kenis; Alexander Richards; Michael C O'Donovan; Jurjen J Luykx; Bart P F Rutten; Sinan Guloksuz Journal: JAMA Psychiatry Date: 2020-12-01 Impact factor: 21.596
Authors: Charlotte Gayer-Anderson; Hannah E Jongsma; Marta Di Forti; Diego Quattrone; Eva Velthorst; Lieuwe de Haan; Jean-Paul Selten; Andrei Szöke; Pierre-Michel Llorca; Andrea Tortelli; Celso Arango; Julio Bobes; Miguel Bernardo; Julio Sanjuán; José Luis Santos; Manuel Arrojo; Mara Parellada; Ilaria Tarricone; Domenico Berardi; Mirella Ruggeri; Antonio Lasalvia; Laura Ferraro; Caterina La Cascia; Daniele La Barbera; Paulo Rossi Menezes; Cristina Marta Del-Ben; Bart P Rutten; Jim van Os; Peter B Jones; Robin M Murray; James B Kirkbride; Craig Morgan Journal: Soc Psychiatry Psychiatr Epidemiol Date: 2020-01-23 Impact factor: 4.328
Authors: Lotta-Katrin Pries; Agustin Lage-Castellanos; Philippe Delespaul; Gunter Kenis; Jurjen J Luykx; Bochao D Lin; Alexander L Richards; Berna Akdede; Tolga Binbay; Vesile Altinyazar; Berna Yalinçetin; Güvem Gümüş-Akay; Burçin Cihan; Haldun Soygür; Halis Ulaş; Eylem Şahin Cankurtaran; Semra Ulusoy Kaymak; Marina M Mihaljevic; Sanja Andric Petrovic; Tijana Mirjanic; Miguel Bernardo; Bibiana Cabrera; Julio Bobes; Pilar A Saiz; María Paz García-Portilla; Julio Sanjuan; Eduardo J Aguilar; José Luis Santos; Estela Jiménez-López; Manuel Arrojo; Angel Carracedo; Gonzalo López; Javier González-Peñas; Mara Parellada; Nadja P Maric; Cem Atbaşoğlu; Alp Ucok; Köksal Alptekin; Meram Can Saka; Celso Arango; Michael O'Donovan; Bart P F Rutten; Jim van Os; Sinan Guloksuz Journal: Schizophr Bull Date: 2019-09-11 Impact factor: 9.306