Brain regional volumetric alterations in adults with bipolar disorder: A meta-analysis

Bipolar Disorder (BD) is a chronic, debilitating mood disorder, yet its structural neurobiology remains incompletely understood. Although prior studies have identified regional brain volumetric differences, many rely on outdated diagnostic criteria, and more recent evidence has not been systematically synthesized. Herein, we aim to meta-analytically synthesize evidence on brain structural alterations in adults with BD using DSM-IV to DSM-5-TR criteria.

Systematic search of PubMed and OVID databases was conducted from inception to February 20, 2026. Eligible studies examined structural or volumetric brain differences in adults with BD. A systematic review and meta-analysis were conducted to estimate standardized mean differences, and variability was assessed. Effect sizes were pooled using a multivariate random-effects meta-analysis. Risk of bias and heterogeneity were assessed using established methods.

BD was associated with significantly greater cerebrospinal fluid (CSF), intracranial, and right lateral ventricle volumes compared with controls, which may reflect altered intracranial composition and potential reductions in brain parenchymal volume. Variability analyses demonstrated significantly greater variability in CSF and intracranial volumes among individuals with BD, while other regions showed no significant differences. Moderate between-study heterogeneity was observed (I² ≈ 51%), and there was no significant evidence of publication bias.

These findings suggest that specific structural alterations, particularly increased CSF and ventricular volumes which may reflect underlying brain tissue loss, may characterize BD; however, substantial variability exists across individuals and brain regions. This heterogeneity highlights the complexity of BD neurobiology and underscores the need for larger, methodologically consistent studies to better characterize structural changes and their clinical implications.