PT - JOURNAL ARTICLE AU - Nils Opel AU - Micah Cearns AU - Scott Clark AU - Catherine Toben AU - Dominik Grotegerd AU - Walter Heindel AU - Harald Kugel AU - Anja Teuber AU - Heike Minnerup AU - Klaus Berger AU - Udo Dannlowski AU - Bernhard T. Baune TI - Large-scale evidence for an association between low-grade peripheral inflammation and brain structural alterations in major depression in the BiDirect study AID - 10.1503/jpn.180208 DP - 2019 Nov 01 TA - Journal of Psychiatry and Neuroscience PG - 423--431 VI - 44 IP - 6 4099 - http://jpn.ca/content/44/6/423.short 4100 - http://jpn.ca/content/44/6/423.full SO - J Psychiatry Neurosci2019 Nov 01; 44 AB - 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.