The association between C-reactive protein and neuroimaging findings in mood disorders: A review of structural and diffusion MRI studies

1. J Affect Disord. 2025 Jul 15;381:643-658. doi: 10.1016/j.jad.2025.03.175. Epub
2025 Apr 4.

The association between C-reactive protein and neuroimaging findings in mood
disorders: A review of structural and diffusion MRI studies.

Valizadeh P(1), Jannatdoust P(1), Ghadimi DJ(2), Tahamtan M(3), Darmiani K(1),
Shahsavarhaghighi S(1), Rezaei S(4), Aarabi MH(5), Cattarinussi G(6), Sambataro
F(6), Nosari G(7), Delvecchio G(8).

Author information:
(1)School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
(2)School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran,
Iran.
(3)School of Medicine, Tehran University of Medical Sciences, Tehran, Iran;
Advanced Diagnostic and Interventional Radiology Research Center (ADIR), Tehran
University of Medical Science, Tehran, Iran.
(4)Department of Radiology, Medical School, Tabriz University of Medical
Sciences, Tabriz, Iran.
(5)Department of Neuroscience, University of Padova, Padova, Italy.
(6)Department of Neuroscience, University of Padova, Padova, Italy; Padova
Neuroscience Center (PNC), University of Padova, Padova, Italy.
(7)Department of Neurosciences and Mental Health, Fondazione IRCCS Ca’ Granda
Ospedale Maggiore Policlinico, Milan, Italy. Electronic address:
.
(8)Department of Neurosciences and Mental Health, Fondazione IRCCS Ca’ Granda
Ospedale Maggiore Policlinico, Milan, Italy.

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.

Copyright © 2025 Elsevier B.V. All rights reserved.

DOI: 10.1016/j.jad.2025.03.175
PMID: 40189071 [Indexed for MEDLINE]

Conflict of interest statement: Declaration of competing interest All authors
declare no competing interests.

Auteurs Bordeaux Neurocampus