title: T helper 17 cells may drive neuroprogression in major depressive disorder: Proposal of an integrative model.
abstract: The exact pathophysiology of major depressive disorder (MDD) remains elusive. The monoamine theory, which hypothesizes that MDD emerges as a result of dysfunctional serotonergic, dopaminergic and noradrenergic pathways, has guided the therapy of this illness for several decades. More recently, the involvement of activated immune, oxidative and nitrosative stress pathways and of decreased levels of neurotrophic factors has provided emerging insights regarding the pathophysiology of MDD, leading to integrated theories emphasizing the complex interplay of these mechanisms that could lead to neuroprogression. In this review, we propose an integrative model suggesting that T helper 17 (Th17) cells play a pivotal role in the pathophysiology of MDD through (i) microglial activation, (ii) interactions with oxidative and nitrosative stress, (iii) increases of autoantibody production and the propensity for autoimmunity, (iv) disruption of the blood-brain barrier, and (v) dysregulation of the gut mucosa and microbiota. The clinical and research implications of this model are discussed.
authors.affiliation: Womens Health Concerns Clinic, St. Joseph's Healthcare Hamilton, MiNDS Program, McMaster University; Hamilton, Ontario, Canada.
authors.forename: Anastasiya
authors.initials: A
authors.lastname: Slyepchenko
authors.affiliation: IMPACT Strategic Research Centre, Deakin University, School of Medicine and Barwon Health, Geelong, VIC, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Maes
authors.affiliation: Department of Clinical Medicine and Translational Psychiatry Research Group, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil.
authors.forename: Cristiano A
authors.initials: CA
authors.lastname: Köhler
authors.affiliation: CRC Scotland & London, Eccleston Square, London, UK.
authors.forename: George
authors.initials: G
authors.lastname: Anderson
authors.affiliation: Center for Translational Psychiatry, Department of Psychiatry and Behavioral Sciences, The University of Texas Medical School at Houston, Houston, TX, USA; Laboratory of Neurosciences, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil.
authors.forename: João
authors.initials: J
authors.lastname: Quevedo
authors.affiliation: Department of Clinical Medicine and Translational Psychiatry Research Group, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil.
authors.forename: Gilberto S
authors.initials: GS
authors.lastname: Alves
authors.affiliation: IMPACT Strategic Research Centre, Deakin University, School of Medicine and Barwon Health, Geelong, VIC, Australia; Department of Psychiatry, Florey Institute of Neuroscience and Mental Health, Orygen, The National Centre of Excellence in Youth Mental Health and Orygen Youth Health Research Centre, University of Melbourne, Parkville, VIC, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Berk
authors.affiliation: IMPACT Strategic Research Centre, Deakin University, School of Medicine and Barwon Health, Geelong, VIC, Australia; Laboratory of Calcium Binding Proteins in the Central Nervous System, Department of Biochemistry, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Brisa S
authors.initials: BS
authors.lastname: Fernandes
authors.affiliation: Department of Clinical Medicine and Translational Psychiatry Research Group, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil. Electronic address: andrefc7@terra.com.br.
authors.forename: André F
authors.initials: AF
authors.lastname: Carvalho
mesh_terms: D000818:Animals; D003865:Major Depressive Disorder / Q000276:immunology*; D006801:Humans; D058504:Th17 Cells / Q000502:physiology*
keywords: Autoimmunity; Depression; Inflammation; Microbiota; Neuroprogression; Neurotrophins; Oxidative stress; Psychiatry; Th17 cells