Associations between structural brain measures and cognitive function in bipolar disorder: a systematic review and meta-analysis.

Bipolar disorder (BD) is a chronic condition characterized by recurrent mood episodes and persistent cognitive deficits that span multiple domains, ultimately impacting daily functioning. Understanding the neural underpinnings of these impairments is crucial. In a systematic review and meta-analysis examining 80 studies (with 50 meeting criteria for meta-analysis) of adults with BD, relationships between structural brain measures and cognitive performance were evaluated. Participants were diagnosed according to standard criteria, underwent structural and diffusion-weighted MRI, and completed standardized cognitive assessments. The meta-analyses indicated significant associations between both grey matter and white matter indices and cognitive functioning, reflected in moderate effect sizes. Notably, these associations exhibited substantial heterogeneity. Meta-regression revealed that bipolar subtype and current mood state moderated the observed brain-cognition relationships, with bipolar I and euthymic individuals showing higher associations with grey matter metrics. Cognitive domain differences also played a key role, indicating that certain cognitive functions are more strongly linked to structural brain measures than others. Brain networks emerged as a global influence on cognition, with limited differences in pairwise comparisons. Age, sex, psychosis, and mania were not found to significantly moderate these relationships. Overall, this work suggests that structural alterations in grey and white matter in individuals with BD may contribute meaningfully to cognitive difficulties, while brain networks may provide a broad integrative framework for these associations. These findings underscore the importance of considering both global and specific neural factors when exploring the pathophysiology of cognitive impairment in BD.