Peripheral Alterations in Cytokine and Chemokine Levels After Antidepressant Drug Treatment for Major Depressive Disorder: Systematic Review and Meta-Analysis.

Cristiano A Köhler, Thiago H Freitas, Brendon Stubbs, Michael Maes, Marco Solmi, Nicola Veronese, Nayanna Q de Andrade, Gerwyn Morris, Brisa S Fernandes, André R Brunoni, Nathan Herrmann, Charles L Raison, Brian J Miller, Krista L Lanctôt, André F Carvalho

Journal: Molecular neurobiology 2019;55(5):4195-4206

PMID: 28612257

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Abstract

Mounting evidence suggests that aberrations in immune-inflammatory pathways contribute to the pathophysiology of major depressive disorder (MDD), and individuals with MDD may have elevated levels of predominantly pro-inflammatory cytokines and C-reactive protein. In addition, previous meta-analyses suggest that antidepressant drug treatment may decrease peripheral levels of interleukin-1 beta (IL-1β) and IL-6. Recently, several new studies examining the effect of antidepressants on these cytokines have been published, and so we performed an updated meta-analysis of studies that measured peripheral levels of cytokines and chemokines during antidepressant treatment in patients with MDD. The PubMed/MEDLINE, EMBASE, and PsycInfo databases were searched from inception through March 9, 2017. Forty-five studies met inclusion criteria (N = 1517). Peripheral levels of IL-6, tumor necrosis factor-alpha (TNF-α), IL-1β, IL-10, IL-2, IL-4, interferon-γ, IL-8, the C-C motif ligand 2 chemokine (CCL-2), CCL-3, IL-1 receptor antagonist, IL-13, IL-17, IL-5, IL-7, and the soluble IL-2 receptor were measured in at least three datasets and thus were meta-analyzed. Antidepressant treatment significantly decreased peripheral levels of IL-6 (Hedges g = -0.454, P <0.001), TNF-α (g = -0.202, P = 0.015), IL-10 (g = -0.566, P = 0.012), and CCL-2 (g = -1.502, P = 0.006). These findings indicate that antidepressants decrease several markers of peripheral inflammation. However, this meta-analysis did not provide evidence that reductions in peripheral inflammation are associated with antidepressant treatment response although few studies provided separate data for treatment responders and non-responders.

Address: Translational Psychiatry Research Group and Department of Clinical Medicine, Faculty of Medicine, Fortaleza, CE, Brazil.; Physiotherapy Department, South London and Maudsley, NHS Foundation Trust, London, UK.; Health Service and Population Research Department, Institute of Psychiatry, Psychology and Neuroscience, King's College London, De Crespigny Park, London, UK.; IMPACT Strategic Research Centre, School of Medicine, Deakin University, 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 Neurosciences, University of Padova, Padova, Italy.; Institute of Clinical Research and Education in Medicine (IREM), Padua, Italy.; Institute of Clinical Research and Education in Medicine (IREM), Padua, Italy.; National Research Council, Neuroscience Institute, Aging Branch, Via Giustiniani 2, 35128, Padova, Italy.; IMPACT Strategic Research Centre, School of Medicine, Deakin University, Geelong, Australia.; IMPACT Strategic Research Centre, School of Medicine, Deakin University, 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.; Center for Clinical and Epidemiological Research & Interdisciplinary Center for Applied Neuromodulation (CINA), University Hospital, University of São Paulo, São Paulo, Brazil.; Service of Interdisciplinary Neuromodulation (SIN), Department and Institute of Psychiatry, Faculty of Medicine of University of São Paulo, São Paulo, Brazil.; Laboratory of Neuroscience (LIM27), Department and Institute of Psychiatry, University of São Paulo, São Paulo, Brazil.; 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, 1300 Linden Drive, Room 4174, Madison, WI, 53705, USA.; Department of Psychiatry, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, 53705, USA.; Department of Psychiatry & Health Behavior, Georgia Regents University, Augusta, GA, USA.; Neuropsychopharmacology Research Group, Hurvitz Brain Sciences Program Sunnybrook Research Institute, Toronto, ON, Canada.; Department of Psychiatry, University of Toronto, Toronto, ON, Canada.; Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada.; Translational Psychiatry Research Group and Department of Clinical Medicine, Faculty of Medicine, Fortaleza, CE, Brazil. [email protected].; Department of Clinical Medicine, Faculty of Medicine, Federal University of Ceará, Rua Prof. Costa Mendes, 1608, 4° andar, Fortaleza, CE, 60430-040, Brazil. [email protected].

DOI: 10.1007/s12035-017-0632-1