{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T07:10:11Z","timestamp":1790233811776,"version":"4.1.0"},"reference-count":50,"publisher":"Canadian Science Publishing","issue":"6","license":[{"start":{"date-parts":[[2019,11,1]],"date-time":"2019-11-01T00:00:00Z","timestamp":1572566400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.nrcresearchpress.com\/page\/about\/CorporateTextAndDataMining"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Psychiatry Neurosci"],"published-print":{"date-parts":[[2019,11]]},"abstract":"<jats:sec><jats:title>Background:<\/jats:title><jats:p> 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. <\/jats:p><\/jats:sec><jats:sec><jats:title>Methods:<\/jats:title><jats:p> 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. <\/jats:p><\/jats:sec><jats:sec><jats:title>Results:<\/jats:title><jats:p> Compared with healthy controls (age [mean \u00b1 standard deviation] 52.57 \u00b1 7.94 yr; 50% male), patients with MDD (49.14 \u00b1 7.28 yr, 39% male) exhibited significantly increased hsCRP levels ( Z = \u22125.562, p &lt; 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; t<jats:sub>1,501<\/jats:sub> = 5.15; k = 92; p<jats:sub>FWE<\/jats:sub> &lt; 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. <\/jats:p><\/jats:sec><jats:sec><jats:title>Limitations:<\/jats:title><jats:p> This study had a cross-sectional design. <\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion:<\/jats:title><jats:p> 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. <\/jats:p><\/jats:sec>","DOI":"10.1503\/jpn.180208","type":"journal-article","created":{"date-parts":[[2019,10,29]],"date-time":"2019-10-29T10:26:28Z","timestamp":1572344788000},"page":"423-431","source":"Crossref","is-referenced-by-count":55,"title":["Large-scale evidence for an association between low-grade peripheral inflammation and brain structural alterations in major depression in the BiDirect study"],"prefix":"10.1139","volume":"44","author":[{"given":"Nils","family":"Opel","sequence":"first","affiliation":[{"name":"From the Department of Psychiatry and Psychotherapy, University of M\u00fcnster, Germany (Opel, Grotegerd, Dannlowski, Baune) the Interdisciplinary Centre for Clinical Research (IZKF), University of M\u00fcnster, Germany (Opel); the Discipline of Psychiatry, School of Medicine, University of Adelaide, Australia (Cearns, Clark, Toben); the Institute of Clinical Radiology, University of M\u00fcnster, Germany (Heindel, Kugel); the Institute of Epidemiology and Social Medicine, University of M\u00fcnster, 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)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micah","family":"Cearns","sequence":"additional","affiliation":[{"name":"From the Department of Psychiatry and Psychotherapy, University of M\u00fcnster, Germany (Opel, Grotegerd, Dannlowski, Baune) the Interdisciplinary Centre for Clinical Research (IZKF), University of M\u00fcnster, Germany (Opel); the Discipline of Psychiatry, School of Medicine, University of Adelaide, Australia (Cearns, Clark, Toben); the Institute of Clinical Radiology, University of M\u00fcnster, Germany (Heindel, Kugel); the Institute of Epidemiology and Social Medicine, University of M\u00fcnster, 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)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott","family":"Clark","sequence":"additional","affiliation":[{"name":"From the Department of Psychiatry and Psychotherapy, University of M\u00fcnster, Germany (Opel, Grotegerd, Dannlowski, Baune) the Interdisciplinary Centre for Clinical Research (IZKF), University of M\u00fcnster, Germany (Opel); the Discipline of Psychiatry, School of Medicine, University of Adelaide, Australia (Cearns, Clark, Toben); the Institute of Clinical Radiology, University of M\u00fcnster, Germany (Heindel, Kugel); the Institute of Epidemiology and Social Medicine, University of M\u00fcnster, 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)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Toben","sequence":"additional","affiliation":[{"name":"From the Department of Psychiatry and Psychotherapy, University of M\u00fcnster, Germany (Opel, Grotegerd, Dannlowski, Baune) the Interdisciplinary Centre for Clinical Research (IZKF), University of M\u00fcnster, Germany (Opel); the Discipline of Psychiatry, School of Medicine, University of Adelaide, Australia (Cearns, Clark, Toben); the Institute of Clinical Radiology, University of M\u00fcnster, Germany (Heindel, Kugel); the Institute of Epidemiology and Social Medicine, University of M\u00fcnster, 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)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominik","family":"Grotegerd","sequence":"additional","affiliation":[{"name":"From the Department of Psychiatry and Psychotherapy, University of M\u00fcnster, Germany (Opel, Grotegerd, Dannlowski, Baune) the Interdisciplinary Centre for Clinical Research (IZKF), University of M\u00fcnster, Germany (Opel); the Discipline of Psychiatry, School of Medicine, University of Adelaide, Australia (Cearns, Clark, Toben); the Institute of Clinical Radiology, University of M\u00fcnster, Germany (Heindel, Kugel); the Institute of Epidemiology and Social Medicine, University of M\u00fcnster, 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)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter","family":"Heindel","sequence":"additional","affiliation":[{"name":"From the Department of Psychiatry and Psychotherapy, University of M\u00fcnster, Germany (Opel, Grotegerd, Dannlowski, Baune) the Interdisciplinary Centre for Clinical Research (IZKF), University of M\u00fcnster, Germany (Opel); the Discipline of Psychiatry, School of Medicine, University of Adelaide, Australia (Cearns, Clark, Toben); the Institute of Clinical Radiology, University of M\u00fcnster, Germany (Heindel, Kugel); the Institute of Epidemiology and Social Medicine, University of M\u00fcnster, Germany (Teuber, Minnerup, Berger); the Department of Psychiatry, Melbourne Medical School, the University of Melbourne, Victoria, Australia (Baune); and 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