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We conducted a \u201cmeta\u2010umbrella\u201d systematic synthesis of umbrella reviews, which are systematic reviews of meta\u2010analyses of individual studies, by searching international databases from inception to January 1, 2021. We included umbrella reviews on non\u2010purely genetic risk or protective factors for any ICD\/DSM mental disorders, applying an established classification of the credibility of the evidence: class I (convincing), class II (highly suggestive), class III (suggestive), class IV (weak). Sensitivity analyses were conducted on prospective studies to test for temporality (reverse causation), TRANSD criteria were applied to test transdiagnosticity of factors, and A Measurement Tool to Assess Systematic Reviews (AMSTAR) was employed to address the quality of meta\u2010analyses. Fourteen eligible umbrella reviews were retrieved, summarizing 390 meta\u2010analyses and 1,180 associations between putative risk or protective factors and mental disorders. We included 176 class I to III evidence associations, relating to 142 risk\/protective factors. The most robust risk factors (class I or II, from prospective designs) were 21. For dementia, they included type 2 diabetes mellitus (risk ratio, RR from 1.54 to 2.28), depression (RR from 1.65 to 1.99) and low frequency of social contacts (RR=1.57). For opioid use disorders, the most robust risk factor was tobacco smoking (odds ratio, OR=3.07). For non\u2010organic psychotic disorders, the most robust risk factors were clinical high risk state for psychosis (OR=9.32), cannabis use (OR=3.90), and childhood adversities (OR=2.80). For depressive disorders, they were widowhood (RR=5.59), sexual dysfunction (OR=2.71), three (OR=1.99) or four\u2010five (OR=2.06) metabolic factors, childhood physical (OR=1.98) and sexual (OR=2.42) abuse, job strain (OR=1.77), obesity (OR=1.35), and sleep disturbances (RR=1.92). For autism spectrum disorder, the most robust risk factor was maternal overweight pre\/during pregnancy (RR=1.28). For attention\u2010deficit\/hyperactivity disorder (ADHD), they were maternal pre\u2010pregnancy obesity (OR=1.63), maternal smoking during pregnancy (OR=1.60), and maternal overweight pre\/during pregnancy (OR=1.28). Only one robust protective factor was detected: high physical activity (hazard ratio, HR=0.62) for Alzheimer\u2019s disease. In all, 32.9% of the associations were of high quality, 48.9% of medium quality, and 18.2% of low quality. Transdiagnostic class I\u2010III risk\/protective factors were mostly involved in the early neurodevelopmental period. The evidence\u2010based atlas of key risk and protective factors identified in this study represents a benchmark for advancing clinical characterization and research, and for expanding early intervention and preventive strategies for mental disorders.<\/jats:p>","DOI":"10.1002\/wps.20894","type":"journal-article","created":{"date-parts":[[2021,9,10]],"date-time":"2021-09-10T03:16:40Z","timestamp":1631243800000},"page":"417-436","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":286,"title":["Risk and protective factors for mental disorders beyond genetics: an evidence\u2010based atlas"],"prefix":"10.1002","volume":"20","author":[{"given":"Celso","family":"Arango","sequence":"first","affiliation":[{"name":"Department of Child and Adolescent Psychiatry Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Mara\u00f1\u00f3n  Madrid Spain"},{"name":"Health Research Institute (IiGSM), School of Medicine, Universidad Complutense de Madrid  Madrid Spain"},{"name":"Biomedical Research Center for Mental Health (CIBERSAM)  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Dragioti","sequence":"additional","affiliation":[{"name":"Pain and Rehabilitation Centre and Department of Health, Medicine and Caring Sciences Link\u00f6ping University  Link\u00f6ping Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Solmi","sequence":"additional","affiliation":[{"name":"Early Psychosis: Interventions and Clinical\u2010detection (EPIC) Lab, Department of Psychosis Studies Institute of Psychiatry, Psychology &amp; 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