Nils Opel1, Micah Cearns1, Scott Clark1, Catherine Toben1, Dominik Grotegerd1, Walter Heindel1, Harald Kugel1, Anja Teuber1, Heike Minnerup1, Klaus Berger1, Udo Dannlowski1, Bernhard T. Baune1. 1. From 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).
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.
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.
Authors: Sarah R Horn; Madison M Long; Benjamin W Nelson; Nicholas B Allen; Philip A Fisher; Michelle L Byrne Journal: Brain Behav Immun Date: 2018-06-19 Impact factor: 7.217
Authors: Brisa S Fernandes; Johann Steiner; Marc L Molendijk; Seetal Dodd; Patricia Nardin; Carlos-Alberto Gonçalves; Felice Jacka; Cristiano A Köhler; Chandan Karmakar; André F Carvalho; Michael Berk Journal: Lancet Psychiatry Date: 2016-11-10 Impact factor: 27.083
Authors: A L Jefferson; J M Massaro; P A Wolf; S Seshadri; R Au; R S Vasan; M G Larson; J B Meigs; J F Keaney; I Lipinska; S Kathiresan; E J Benjamin; C DeCarli Journal: Neurology Date: 2007-03-27 Impact factor: 9.910
Authors: Rita Haapakoski; Julia Mathieu; Klaus P Ebmeier; Harri Alenius; Mika Kivimäki Journal: Brain Behav Immun Date: 2015-06-09 Impact factor: 7.217
Authors: T Frodl; A Carballedo; M M Hughes; K Saleh; A Fagan; N Skokauskas; D M McLoughlin; J Meaney; V O'Keane; T J Connor Journal: Transl Psychiatry Date: 2012-03-13 Impact factor: 6.222
Authors: Hayley F North; Jason Bruggemann; Vanessa Cropley; Vaidy Swaminathan; Suresh Sundram; Rhoshel Lenroot; Avril M Pereira; Andrew Zalesky; Chad Bousman; Christos Pantelis; Thomas W Weickert; Cynthia Shannon Weickert Journal: Eur Arch Psychiatry Clin Neurosci Date: 2021-03-24 Impact factor: 5.270
Authors: Michelle M Karth; Brittany J Baugher; Nicole Daly; Melinda D Karth; Stephen C Gironda; Benjamin D Sachs Journal: Front Mol Neurosci Date: 2019-12-11 Impact factor: 5.639
Authors: Claire Green; Xueyi Shen; Anna J Stevenson; Eleanor L S Conole; Mathew A Harris; Miruna C Barbu; Emma L Hawkins; Mark J Adams; Robert F Hillary; Stephen M Lawrie; Kathryn L Evans; Rosie M Walker; Stewart W Morris; David J Porteous; Joanna M Wardlaw; J Douglas Steele; Gordon D Waiter; Anca-Larisa Sandu; Archie Campbell; Riccardo E Marioni; Simon R Cox; Jonathan Cavanagh; Andrew M McIntosh; Heather C Whalley Journal: Brain Behav Immun Date: 2020-11-19 Impact factor: 7.217