Meta-Analytic Evidence of Clinical, Cognitive, Biological and Treatment Characteristics of Bipolar Spectrum Disorder in Children and Adolescents: Results From an Umbrella Review.

OBJECTIVE

To comprehensively synthesize the meta-analytic evidence regarding bipolar spectrum disorder (BSD) in children and adolescents.

METHOD: PRISMA-compliant umbrella review (PROSPERO:CRD420250651065) across multiple databases to identify meta-analyses involving children and adolescents with BSD. Literature search, screening, data extraction, and quality assessment (via AMSTAR-2) were performed independently. Findings were synthesized and grouped according to key clinical, cognitive, biological and treatment domains.

RESULTS

Fifty-two meta-analyses were included (k=754, N=59,967, age=13.0 years, 44.8% female participants). Most reported symptoms were increased energy (79%, 95% confidence interval (CI)=61-93%), irritability (77%, 95%CI=64-88%), and mood lability (76%, 95%CI=55-92%). Psychiatric comorbidities were common, with attention-deficit/hyperactivity disorder being most frequent (53%, 95%CI=36-70%). Treatment delay was longer in children and adolescents than in adults with BSD (SMD=0.39, 95%CI=0.15-0.64). 26.2% (95%CI=24.4-28.0) of children and adolescents with BSD attempted suicide at least once, with higher risk vs. children and adolescents with depression (OR=1.59; 95%CI=1.24-2.05) and adult-BSD (OR=1.68, 95%CI=1.29-2.18). Compared to healthy controls (HCs), children and adolescents with BSD showed neurocognitive impairments. Abnormalities in neuroimaging markers were significant in children and adolescents with BSD vs. HCs, children and adolescents with depression and adult-BSD. Second-generation antipsychotics (SMD=0.68, 95%CI=0.51-0.86) and mood stabilizers (SMD=0.61, 95%CI=0.40-0.82) were superior for mania vs. placebo. Cognitive behavioral therapy (CBT) was associated with improvements in manic and depressive symptoms.

CONCLUSION

BSD in children and adolescents is linked to illness severity, cognitive deficits, and neuroimaging abnormalities, requiring integrated pharmacological and psychosocial interventions (e.g. CBT). SGAs effectively treat mania, but options for depression remain limited. More prognostic and long-term studies are needed.