title: Peripheral cytokine and chemokine alterations in depression: a meta-analysis of 82 studies.
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).
  
  
  METHODS
  The PubMed/MEDLINE, EMBASE, and PsycINFO databases were searched up until May 30, 2016. Effect sizes were estimated with random-effects models.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Translational Psychiatry Research Group and Department of Clinical Medicine, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil.
authors.forename: C A
authors.initials: CA
authors.lastname: Köhler
authors.affiliation: Translational Psychiatry Research Group and Department of Clinical Medicine, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil.
authors.forename: T H
authors.initials: TH
authors.lastname: Freitas
authors.affiliation: 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.
authors.forename: M
authors.initials: M
authors.lastname: Maes
authors.affiliation: Translational Psychiatry Research Group and Department of Clinical Medicine, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil.
authors.forename: N Q
authors.initials: NQ
authors.lastname: de Andrade
authors.affiliation: Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada.|Neuropsychopharmacology Research Group, Hurvitz Brain Sciences Program Sunnybrook Research Institute, Toronto, ON, Canada.
authors.forename: C S
authors.initials: CS
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: B S
authors.initials: BS
authors.lastname: Fernandes
authors.affiliation: 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.
authors.forename: B
authors.initials: B
authors.lastname: Stubbs
authors.affiliation: Department of Neurosciences, University of Padova, Padova, Italy.|Institute of Clinical Research and Education in Medicine (IREM), Padova, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Solmi
authors.affiliation: Department of Neurosciences, University of Padova, Padova, Italy.|Department of Medicine, DIMED, Geriatrics Section, University of Padova, Padova, Italy.
authors.forename: N
authors.initials: N
authors.lastname: Veronese
authors.affiliation: Neuropsychopharmacology Research Group, Hurvitz Brain Sciences Program Sunnybrook Research Institute, Toronto, ON, Canada.|Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
authors.forename: N
authors.initials: N
authors.lastname: Herrmann
authors.affiliation: 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.
authors.forename: C L
authors.initials: CL
authors.lastname: Raison
authors.affiliation: Department of Psychiatry & Health Behavior, Augusta University, Augusta, GA, USA.
authors.forename: B J
authors.initials: BJ
authors.lastname: Miller
authors.affiliation: 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.
authors.forename: K L
authors.initials: KL
authors.lastname: Lanctôt
authors.affiliation: Translational Psychiatry Research Group and Department of Clinical Medicine, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil.
authors.forename: A F
authors.identifier: http://orcid.org/0000-0001-5593-2778
authors.initials: AF
authors.lastname: Carvalho
mesh_terms: D018925:Chemokines / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism*; D003865:Major Depressive Disorder / Q000276:immunology*; D005260:Female; D006801:Humans; D008297:Male
chemical_list: D018925:Chemokines; D016207:Cytokines
keywords: chemokines; cytokines; depression; inflammation; meta-analysis