Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/122835
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Type: Journal article
Title: Large-scale evidence for an association between low-grade peripheral inflammation and brain structural alterations in major depression in the BiDirect study
Author: Opel, N.
Cearns, M.
Clark, S.
Toben, C.
Grotegerd, D.
Heindel, W.
Kugel, H.
Teuber, A.
Minnerup, H.
Berger, K.
Dannlowski, U.
Baune, B.T.
Citation: Journal of Psyciatry and Neuroscience, 2019; 44(6):423-431
Publisher: Joule Inc; Canadian Medical Association
Issue Date: 2019
ISSN: 1180-4882
1488-2434
Statement of
Responsibility: 
Nils Opel, Micah Cearns, Scott Clark, Catherine Toben, Dominik Grotegerd, Walter Heindel, Harald Kugel, Anja Teuber, Heike Minnerup, Klaus Berger, Udo Dannlowski, Bernhard T. Baune
Abstract: 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.
Rights: © 2019 Joule Inc. or its licensors
RMID: 0030120973
DOI: 10.1503/jpn.180208
Appears in Collections:Medicine publications

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