Related Experiment Video
Updated: Jan 22, 2026
Author Spotlight: Unveiling the Connection Between Sleep Disorders and Cognitive Symptoms in Depression
Published on: April 26, 2024
Large-scale evidence for an association between low-grade peripheral inflammation and brain structural alterations in
Nils Opel1, Micah Cearns1, Scott Clark1
1From the Department of Psychiatry and Psychotherapy, University of Münster, Germany (Opel, Grotegerd, Dannlowski, Baune) the Interdisciplinary Centre for Clinical Research (IZKF), University of Münster, Germany (Opel); the Discipline of Psychiatry, School of Medicine, University of Adelaide, Australia (Cearns, Clark, Toben); the Institute of Clinical Radiology, University of Münster, Germany (Heindel, Kugel); the Institute of Epidemiology and Social Medicine, University of Münster, Germany (Teuber, Minnerup, Berger); the Department of Psychiatry, Melbourne Medical School, the University of Melbourne, Victoria, Australia (Baune); and the Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria, Australia (Baune).
Background:
Preliminary research suggests that major depressive disorder (MDD) is associated with structural alterations in the brain; as well as with low-grade peripheral inflammation. However, even though a link between inflammatory processes and altered brain structural integrity has been purported by experimental research, well-powered studies to confirm this hypothesis in patients with MDD have been lacking. We aimed to investigate the potential association between structural brain alterations and low-grade inflammation as interrelated biological correlates of MDD.
Methods:
In this cross-sectional study, 514 patients with MDD and 359 healthy controls underwent structural MRI. We used voxel-based morphometry to study local differences in grey matter volume. We also assessed serum levels of high-sensitivity C-reactive protein (hsCRP) in each participant.
Results:
Compared with healthy controls (age [mean ± standard deviation] 52.57 ± 7.94 yr; 50% male), patients with MDD (49.14 ± 7.28 yr, 39% male) exhibited significantly increased hsCRP levels (Z = −5.562, p < 0.001) and significantly decreased grey matter volume in the prefrontal cortex and the insula. Prefrontal grey matter volume reductions were significantly associated with higher hsCRP levels in patients with MDD (x = 50, y = 50, z = 8; t1,501 = 5.15; k = 92; pFWE < 0.001). In the MDD sample, the significant negative association between hsCRP and grey matter appeared independent of age, sex, body mass index, current smoking status, antidepressant load, hospitalization and medical comorbidities.
Limitations:
This study had a cross-sectional design.
Conclusion:
The present study highlights the role of reduced grey matter volume and low-grade peripheral inflammation as interrelated biological correlates of MDD. The reported inverse association between peripheral low-grade inflammation and brain structural integrity in patients with MDD translates current knowledge from experimental studies to the bedside.
Related Concept Videos
02:55The Evidence for Evolution
01:13Collagens are the Major Structural Proteins of ECM
Connective tissue proper includes loose...
01:20Anatomy of the Brain: Major Regions
The cerebrum is the largest section of the brain and divides into left and right hemispheres, separated by a deep fissure. The cerebral outer layer of grey matter — the cerebral cortex — comprises elevations called gyri and shallow groves called sulci. The inner portion of white matter includes long nerve fibers known as axons, which connect...
01:38Inflammation
01:11Genome-wide Association Studies-GWAS
GWAS does not require the identification of the target gene involved in...
01:05Long-term Depression