Structural and functional MRI correlates of inflammation in bipolar disorder: A systematic review

Background: Bipolar disorder (BD) is a common affective disorder characterized by recurrent oscillations between mood states and associated with inflammatory diseases and chronic inflammation. However, data on MRI ab-normalities in BD and their relationship with inflammation are heterogeneous and no review has recapitulated them. Methods: In this pre-registered (PROSPERO: CRD42022308461) systematic review we searched Web of Science Core Collection and PubMed for articles correlating functional or structural MRI measures with immune-related markers in BD. Results: We included 23 studies (6 on functional, 16 on structural MRI findings, 1 on both, including 1'233 BD patients). Overall, the quality of the studies included was fair, with a low risk of bias.Limitations: Heterogeneity in the methods and results of the studies and small sample sizes limit the generaliz-ability of the conclusions. Conclusions: A qualitative synthesis suggests that the links between immune traits and functional or structural MRI alterations point toward brain areas involved in affective and somatomotor processing, with a trend toward a negative correlation between peripheral inflammatory markers and brain regions volume. We discuss how disentangling the complex relationship between the immune system and MRI alterations in BD may unveil mechanisms underlying symptoms pathophysiology, potentially with quickly translatable diagnostic, prognostic, and therapeutic implications.