Common or distinct pathways to psychosis? A systematic review of evidence from prospective studies for developmental risk factors and antecedents of the schizophrenia spectrum disorders and affective psychoses


Identifying the unique and shared premorbid indicators of risk for the schizophrenia spectrum disorders (SSD) and affective psychoses (AP) may refine aetiological hypotheses and inform the delivery of universal versus targeted preventive interventions. This systematic review synthesises the available evidence concerning developmental risk factors and antecedents of SSD and AP to identify those with the most robust support, and to highlight remaining evidence gaps.

A systematic search of prospective birth, population, high-risk, and case-control cohorts was conducted in Medline and supplemented by hand searching, incorporating published studies in English with full text available. Inclusion/exclusion decisions and data extraction were completed in duplicate. Exposures included three categories of risk factors and four categories of antecedents, with case and comparison groups defined by adult psychiatric diagnosis. Effect sizes and prevalence rates were extracted, where available, and the strength of evidence synthesised and evaluated qualitatively across the study designs.

Of 1775 studies identified by the search, 127 provided data to the review. Individuals who develop SSD experience a diversity of subtle premorbid developmental deficits and risk exposures, spanning the prenatal period through early adolescence. Those of greatest magnitude (or observed most consistently) included obstetric complications, maternal illness during pregnancy (especially infections), other maternal physical factors, negative family emotional environment, psychopathology and psychotic symptoms, and cognitive and motor dysfunctions. Relatively less evidence has accumulated to implicate this diversity of exposures in AP, and many yet remain unexamined, with the most consistent or strongest evidence to date being for obstetric complications, psychopathology, cognitive indicators and motor dysfunction. Among the few investigations affording direct comparison between SSD and AP, larger effect sizes and a greater number of significant associations are commonly reported for SSD relative to AP.

Shared risk factors for SSD and AP may include obstetric complications, childhood psychopathology, cognitive markers and motor dysfunction, but the capacity to distinguish common versus distinct risk factors/antecedents for SSD and AP is limited by the scant availability of prospective data for AP, and inconsistency in replication. Further studies considering both diagnoses concurrently are needed. Nonetheless, the prevalence of the risk factors/antecedents observed in cases and controls helps demarcate potential targets for preventative interventions for these disorders.