Development and predictors of bipolar disorder in children and adolescents with depressive disorders: a systematic review, meta-analysis, and meta-regression.

Background: Estimating the risk of developing bipolar disorder (BD) in children and adolescents (C&A) with depressive disorders is important to optimize prevention and early intervention efforts. We aimed to quantitatively examine the risk of developing BD from depressive disorders and identify factors which moderate this development.

Methods: In this systematic review and meta-analysis (PROSPERO:CRD42023431301), PubMed and Web-of-Science databases were searched for longitudinal studies reporting the percentage of C&A with ICD/DSM-defined depressive disorders who developed BD during follow-up. Data extraction, random-effects meta-analysis, between-study heterogeneity analysis, quality assessment, sub-group analyses, and meta-regressions were conducted.

Results: Thirty-nine studies were included, including 72,371 individuals (mean age=13.9 years, 57.1% females); 14.7% of C&A with a depressive disorder developed BD after 20.4-288 months: 9.5% developed BD-I (95% CI=4.7 to 18.1); 7.7% developed BD-II (95% CI=3.2% to 17.3%); 19.8% (95% CI=9.9% to 35.6%) of C&A admitted into the hospital with a depressive disorder developed BD. Studies using the DSM (21.6%, 95% CI=20.2% to 23.1%) and studies evaluating C&A with a major depressive disorder only (19.8%, 95% CI=16.8% to 23.1%) found higher rates of development of BD. Younger age at baseline, a history of hospitalization and recruitment from specialized clinics were associated with an increased risk of developing BD at follow-up. Quality of included studies was good in 76.9% of studies.

Conclusions: There is a substantial risk of developing BD in C&A with depressive disorders. This is particularly the case for C&A with MDD, DSM-diagnosed depressive disorders, and C&A admitted into the hospital. Research exploring additional predictors and preventive interventions is crucial.