A systematic meta-review grading the evidence for non-genetic risk factors and putative antecedents of schizophrenia

Introduction: Identifying the relative strength of evidence associated with non-genetic risk factors and putative antecedents of schizophrenia will guide research and may inform the design of early detection and intervention strategies. Aims: To present and quality assess current evidence for non-genetic risk factors and putative antecedents derived from well-conducted systematic reviews that report pooled data. Method: Medline, Embase, CINAHL, Current Contents, and PsycINFO databases were searched systematically, and supplemented by hand searching. Review reporting quality was assessed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses ( PRISMA ) checklist, review methodology was assessed using the Assessment of Multiple Systematic Reviews ( AMSTAR ) checklist, and evidence quality was assessed using the Grading of Recommendations Assessment, Development and Evaluation ( GRADE ) approach. Results: Twenty-four reviews met inclusion criteria. The risk factors with the highest quality evidence, reporting medium effect sizes, were advanced paternal age, obstetric complications, and cannabis use. The strongest evidence among the putative antecedents was identified for motor dysfunction and low IQ. Conclusions: More research is required that applies sound methodological practices, taking into consideration specificity for schizophrenia and possible confounding factors, to robustly identify the non-genetic risk factors and putative antecedents of schizophrenia