Peripheral cytokine and chemokine alterations in depression: a meta-analysis of 82 studies

C A Köhler; T H Freitas; M Maes; N Q de Andrade; C S Liu; B S Fernandes; B Stubbs; M Solmi; N Veronese; N Herrmann; C L Raison; B J Miller; K L Lanctôt; A F Carvalho

doi:10.1111/acps.12698

Peripheral cytokine and chemokine alterations in depression: a meta-analysis of 82 studies

Acta Psychiatr Scand. 2017 May;135(5):373-387. doi: 10.1111/acps.12698. Epub 2017 Jan 25.

Authors

C A Köhler¹, T H Freitas¹, M Maes^{2

3

4

5

6}, N Q de Andrade¹, C S Liu^{7

8}, B S Fernandes^{2

9}, B Stubbs^{10

11}, M Solmi^{12

13}, N Veronese^{12

14}, N Herrmann^{8

15}, C L Raison^{16

17}, B J Miller¹⁸, K L Lanctôt^{7

8

15}, A F Carvalho¹

Affiliations

¹ Translational Psychiatry Research Group and Department of Clinical Medicine, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil.
² Deakin University, IMPACT Strategic Research Centre, School of Medicine, Geelong, Australia.
³ Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
⁴ Department of Psychiatry, Faculty of Medicine, State University of Londrina, Londrina, PR, Brazil.
⁵ Department of Psychiatry, Medical University Plovdiv, Plovdiv, Bulgaria.
⁶ Revitalis, Waalre, The Netherlands.
⁷ Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada.
⁸ Neuropsychopharmacology Research Group, Hurvitz Brain Sciences Program Sunnybrook Research Institute, Toronto, ON, Canada.
⁹ Laboratory of Calcium Binding Proteins in the Central Nervous System, Department of Biochemistry, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
¹⁰ Physiotherapy Department, South London and Maudsley NHS Foundation Trust, Denmark Hill, London, UK.
¹¹ Health Service and Population Research Department, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London, London, UK.
¹² Department of Neurosciences, University of Padova, Padova, Italy.
¹³ Institute of Clinical Research and Education in Medicine (IREM), Padova, Italy.
¹⁴ Department of Medicine, DIMED, Geriatrics Section, University of Padova, Padova, Italy.
¹⁵ Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
¹⁶ Department of Human Development and Family Studies, School of Human Ecology, University of Wisconsin-Madison, Madison, WI, USA.
¹⁷ Department of Psychiatry, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.
¹⁸ Department of Psychiatry & Health Behavior, Augusta University, Augusta, GA, USA.

PMID: 28122130
DOI: 10.1111/acps.12698

Abstract

Objective: To conduct a systematic review and meta-analysis of studies that measured cytokine and chemokine levels in individuals with major depressive disorder (MDD) compared to healthy controls (HCs).

Method: The PubMed/MEDLINE, EMBASE, and PsycINFO databases were searched up until May 30, 2016. Effect sizes were estimated with random-effects models.

Result: Eighty-two studies comprising 3212 participants with MDD and 2798 HCs met inclusion criteria. Peripheral levels of interleukin-6 (IL-6), tumor necrosis factor (TNF)-alpha, IL-10, the soluble IL-2 receptor, C-C chemokine ligand 2, IL-13, IL-18, IL-12, the IL-1 receptor antagonist, and the soluble TNF receptor 2 were elevated in patients with MDD compared to HCs, whereas interferon-gamma levels were lower in MDD (Hedge's g = -0.477, P = 0.043). Levels of IL-1β, IL-2, IL-4, IL-8, the soluble IL-6 receptor (sIL-6R), IL-5, CCL-3, IL-17, and transforming growth factor-beta 1 were not significantly altered in individuals with MDD compared to HCs. Heterogeneity was large (I² : 51.6-97.7%), and sources of heterogeneity were explored (e.g., age, smoking status, and body mass index).

Conclusion: Our results further characterize a cytokine/chemokine profile associated with MDD. Future studies are warranted to further elucidate sources of heterogeneity, as well as biosignature cytokines secreted by other immune cells.

Keywords: chemokines; cytokines; depression; inflammation; meta-analysis.

Publication types

Meta-Analysis
Systematic Review

MeSH terms

Chemokines / metabolism*
Cytokines / metabolism*
Depressive Disorder, Major / immunology*
Female
Humans
Male

Substances

Chemokines
Cytokines