C A Köhler1, T H Freitas1, M Maes2,3,4,5,6, N Q de Andrade1, C S Liu7,8, B S Fernandes2,9, B Stubbs10,11, M Solmi12,13, N Veronese12,14, N Herrmann8,15, C L Raison16,17, B J Miller18, K L Lanctôt7,8,15, A F Carvalho1. 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.
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.
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.
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