Large-scale evidence for an association between low-grade peripheral inflammation and brain structural alterations in major depression in the BiDirect study

Adult Brain / diagnostic imaging C-Reactive Protein / metabolism Case-Control Studies Cerebral Cortex / diagnostic imaging Cross-Sectional Studies Depressive Disorder, Major / diagnostic imaging Female Gray Matter / diagnostic imaging Humans Inflammation / metabolism Male Middle Aged Organ Size Prefrontal Cortex / diagnostic imaging

Journal

Journal of psychiatry & neuroscience : JPN
ISSN: 1488-2434
Titre abrégé: J Psychiatry Neurosci
Pays: Canada
ID NLM: 9107859

Informations de publication

Date de publication:
01 11 2019
Historique:
entrez: 16 7 2019
pubmed: 16 7 2019
medline: 23 6 2020
Statut: ppublish

Résumé

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. 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. 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. This study had a cross-sectional design. 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.

Sections du résumé

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.

Identifiants

DOI: 10.1503/jpn.180208 PMID: 31304733 PMC: PMC6821515
pubmed: 31304733
doi: 10.1503/jpn.180208
pmc: PMC6821515
doi:

Substances chimiques

C-Reactive Protein 9007-41-4

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Pagination

423-431

Informations de copyright

© 2019 Joule Inc. or its licensors

Déclaration de conflit d'intérêts

B. Baune is member of advisory boards, received funding and/or gave presentations for AstraZeneca, Lundbeck, Janssen, Pfizer, Servier, and Wyeth, outside the submitted work. No other competing interests declared.

Références

Lancet Psychiatry. 2016 Dec;3(12):1147-1156
pubmed: 27838212
Psychiatry Res. 1986 May;18(1):65-87
pubmed: 3737788
BMC Psychiatry. 2014 Jun 13;14:174
pubmed: 24924233
Arch Gen Psychiatry. 2008 Apr;65(4):409-15
pubmed: 18391129
Hum Brain Mapp. 2013 Oct;34(10):2418-24
pubmed: 22438310
Brain Behav Immun. 2018 Oct;73:85-114
pubmed: 29928963
Brain Behav Immun. 2015 Oct;49:206-15
pubmed: 26065825
Nat Rev Immunol. 2011 Aug 05;11(9):625-32
pubmed: 21818124
Neurology. 2007 Mar 27;68(13):1032-8
pubmed: 17389308
Transl Psychiatry. 2012 Mar 13;2:e88
pubmed: 22832853
Curr Top Behav Neurosci. 2017;31:221-248
pubmed: 27272069
Mol Psychiatry. 2016 Apr;21(4):554-64
pubmed: 26169974
Mol Psychiatry. 2017 Jun;22(6):900-909
pubmed: 27137745
J Affect Disord. 2016 Sep 15;202:1-9
pubmed: 27253210
Biol Psychiatry. 2006 Oct 15;60(8):803-11
pubmed: 16814258
Neuroimage. 2002 Jan;15(1):273-89
pubmed: 11771995
Biol Psychiatry. 2009 May 1;65(9):732-41
pubmed: 19150053
Prog Neuropsychopharmacol Biol Psychiatry. 2014 Jan 3;48:295-303
pubmed: 23313563
Hum Psychopharmacol. 2014 May;29(3):216-23
pubmed: 24911574
Mol Psychiatry. 2015 Mar;20(3):398-404
pubmed: 24776739
Psychosom Med. 2005 May-Jun;67 Suppl 1:S6-9
pubmed: 15953804
Biol Psychiatry. 2012 Feb 15;71(4):286-93
pubmed: 22112927
Lancet. 2007 Sep 8;370(9590):851-8
pubmed: 17826170
Neuroimage Clin. 2013 Apr 22;2:646-57
pubmed: 24179815
J Neurol Neurosurg Psychiatry. 1960 Feb;23:56-62
pubmed: 14399272
Nat Rev Immunol. 2016 Jan;16(1):22-34
pubmed: 26711676
Brain Behav Immun. 2016 Mar;53:39-48
pubmed: 26546831
Brain Behav Immun. 2017 Mar;61:317-325
pubmed: 28025071
Trends Immunol. 2006 Jan;27(1):24-31
pubmed: 16316783
Nat Genet. 2012 Apr 15;44(5):552-61
pubmed: 22504417
J Neuroinflammation. 2018 May 26;15(1):165
pubmed: 29803226
Mol Psychiatry. 2016 Jun;21(6):806-12
pubmed: 26122586
Biol Psychiatry. 2009 Sep 1;66(5):407-14
pubmed: 19423079
Trends Cogn Sci. 2012 Jan;16(1):61-71
pubmed: 22197477
Neuropsychopharmacology. 2018 Jan;43(2):426-434
pubmed: 28726799
Neuropsychopharmacology. 2015 Jan;40(2):463-71
pubmed: 25074636
Brain Behav Immun. 2017 Feb;60:361-368
pubmed: 27989860
Brain Behav Immun. 2012 Jan;26(1):103-8
pubmed: 21843630
Eur Heart J. 2014 Jun 1;35(21):1365-72
pubmed: 24282187
Neuropsychopharmacology. 2014 Nov;39(12):2723-31
pubmed: 24924799
Sci Rep. 2017 Jul 14;7(1):5434
pubmed: 28710424
BMC Med. 2011 May 03;9:47
pubmed: 21539732
Ann N Y Acad Sci. 2004 Dec;1032:1-7
pubmed: 15677391
JAMA Psychiatry. 2014 Dec 1;71(12):1381-91
pubmed: 25322082
Brain Behav Immun. 2016 Nov;58:1-8
pubmed: 26802985
Biol Psychiatry. 2003 Aug 1;54(3):241-7
pubmed: 12893100
J Neurosci. 2009 Feb 18;29(7):2089-102
pubmed: 19228962

Auteurs

Nils Opel (N)

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).

Micah Cearns (M)

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).

Scott Clark (S)

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).

Catherine Toben (C)

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).

Dominik Grotegerd (D)

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).

Walter Heindel (W)

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).

Harald Kugel (H)

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).

Anja Teuber (A)

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).

Heike Minnerup (H)

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).

Klaus Berger (K)

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).

Udo Dannlowski (U)

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).

Bernhard T. Baune (BT)

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).

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female

Evaluation of Low-Value Services Across Major Medicare Advantage Insurers and Traditional Medicare.

Ciara Duggan, Adam L Beckman, Ishani Ganguli et al.
1.00
Humans United States Aged Cross-Sectional Studies Medicare Part C

Effectiveness of Virtual Yoga for Chronic Low Back Pain: A Randomized Clinical Trial.

Hallie Tankha, Devyn Gaskins, Amanda Shallcross et al.
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH

questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Large-scale evidence for an association...
questionsmedicales.fr › Système nerveux › Système nerveux central › Encéphale › Large-scale evidence for an association...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines du sang › Immunoprotéines › Protéine C-réactive › Large-scale evidence for an association...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études cas-témoins › Large-scale evidence for an association...
questionsmedicales.fr › Système nerveux › Système nerveux central › Encéphale › Prosencéphale › Télencéphale › Cerveau › Cortex cérébral › Large-scale evidence for an association...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études transversales › Large-scale evidence for an association...
questionsmedicales.fr › Troubles mentaux › Troubles de l'humeur › Trouble dépressif › Trouble dépressif majeur › Large-scale evidence for an association...
questionsmedicales.fr › Système nerveux › Système nerveux central › Moelle spinale › Substance grise › Large-scale evidence for an association...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Large-scale evidence for an association...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Inflammation › Large-scale evidence for an association...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Adulte d'âge moyen › Large-scale evidence for an association...
questionsmedicales.fr › Phénomènes physiologiques › Croissance et développement › Croissance › Taille d'organe › Large-scale evidence for an association...
questionsmedicales.fr › Système nerveux › Système nerveux central › Encéphale › Prosencéphale › Télencéphale › Cerveau › Cortex cérébral › Lobe frontal › Cortex préfrontal › Large-scale evidence for an association...