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

Journal: Acta psychiatrica Scandinavica 2017;135(5):373-387

PMID: 28122130

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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 (I : 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.

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

DOI: 10.1111/acps.12698