Antecedents of major depressive, bipolar, and psychotic disorders: a systematic review and meta-analysis of prospective studies

Major depressive, bipolar, or psychotic disorders are preceded by earlier manifestations in behaviours and experiences. We present a synthesis of evidence on associations between person-level antecedents (behaviour, performance, psychopathology) in childhood, adolescence, or early adulthood and later onsets of major depressive disorder, bipolar disorder, or psychotic disorder based on prospective studies published up to September 16, 2022. We screened 11,342 records, identified 460 eligible publications, and extracted 570 risk ratios quantifying the relationships between 52 antecedents and onsets in 198 unique samples with prospective follow-up of 122,766 individuals from a mean age of 12.4 to 24.8, for 1,522,426 person years of follow-up. We completed meta-analyses of 12 antecedents with adequate data. Psychotic symptoms, depressive symptoms, anxiety, disruptive behaviors, affective lability, and sleep problems were transdiagnostic antecedents associated with onsets of depressive, bipolar, and psychotic disorders. Attention-deficit/hyperactivity and hypomanic symptoms specifically predicted bipolar disorder. While transdiagnostic and diagnosis-specific antecedents inform targeted prevention and help understand pathogenic mechanisms, extensive gaps in evidence indicate potential for improving early risk identification.