Mood disorders, including major depressive disorder (MDD) and bipolar disorder (BD), often share structural brain alterations, which may be linked to peripheral inflammation. In this regard, C-Reactive Protein (CRP) has been associated with these alterations. This review explores the relationship between CRP levels and neuroimaging findings in mood disorders using structural and diffusion Magnetic Resonance Imaging (MRI).

Following PRISMA guidelines, a systematic search was conducted through Scopus, PubMed, Web of Science, and Embase before September 2024, focusing on studies evaluating associations between CRP levels and structural and/or microstructural brain alterations in mood disorders.

The present systematic review included 20 studies examining the associations between peripheral CRP levels or DNA methylation-based CRP (DNAm CRP) signatures and structural brain alterations in mood disorders. Findings showed considerable variability; however, consistent patterns emerged, linking higher CRP levels to reduced grey matter volumes and cortical thinning, particularly in the prefrontal cortex (PFC), hippocampus, entorhinal cortex, insula, and caudate. Diffusion-based imaging consistently indicated reduced white matter integrity, with significant effects in key tracts such as the internal capsule, cingulum bundle, and corpus callosum (CC).

Overall, these findings suggest that systemic inflammation, reflected by elevated CRP or DNAm CRP, contributes to structural alterations indicative of neurodegeneration and compromised axonal integrity in mood disorders. Discrepancies among studies highlight potential influences of disease severity, treatment history, and distinct inflammatory mediators. Future research employing standardized imaging protocols and longitudinal designs is essential to clarify inflammation's mechanistic roles and identify reliable biomarkers of structural brain alterations in mood disorders.