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The Association Between C-Reactive Protein and Neuroimaging Findings in Mood Disorders: A Review of Structural and Diffusion Mri Studies Publisher Pubmed



Valizadeh P1 ; Jannatdoust P1 ; Ghadimi DJ2 ; Tahamtan M1, 3 ; Darmiani K1 ; Shahsavarhaghighi S1 ; Rezaei S4 ; Aarabi MH5 ; Cattarinussi G5, 6 ; Sambataro F5, 6 ; Nosari G7 ; Delvecchio G7
Authors
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Authors Affiliations
  1. 1. School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  3. 3. Advanced Diagnostic and Interventional Radiology Research Center (ADIR), Tehran University of Medical Science, Tehran, Iran
  4. 4. Department of Radiology, Medical School, Tabriz University of Medical Sciences, Tabriz, Iran
  5. 5. Department of Neuroscience, University of Padova, Padova, Italy
  6. 6. Padova Neuroscience Center (PNC), University of Padova, Padova, Italy
  7. 7. Department of Neurosciences and Mental Health, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy

Source: Journal of Affective Disorders Published:2025


Abstract

Background: 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). Methods: 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. Results: 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). Conclusions: 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. © 2025 Elsevier B.V.
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