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T helper 17 cells may drive neuroprogression in major depressive disorder: proposal of an integrative model

Slyepchenko, Anastasiya, Maes, Michael, Köhler, Cristiano A., Anderson, Goerge, Quevedo, Joao, Alves, Gilberto S., Berk, Michael, Fernandes, Brisa S. and Carvalho, Andre F. 2016, T helper 17 cells may drive neuroprogression in major depressive disorder: proposal of an integrative model, Neuroscience and biobehavioral reviews, vol. 64, pp. 83-100, doi: 10.1016/j.neubiorev.2016.02.002.

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Title T helper 17 cells may drive neuroprogression in major depressive disorder: proposal of an integrative model
Author(s) Slyepchenko, Anastasiya
Maes, Michael
Köhler, Cristiano A.
Anderson, Goerge
Quevedo, Joao
Alves, Gilberto S.
Berk, MichaelORCID iD for Berk, Michael orcid.org/0000-0002-5554-6946
Fernandes, Brisa S.ORCID iD for Fernandes, Brisa S. orcid.org/0000-0002-3797-7582
Carvalho, Andre F.
Journal name Neuroscience and biobehavioral reviews
Volume number 64
Start page 83
End page 100
Total pages 18
Publisher Elsevier
Place of publication Amsterdam, The Netherlands
Publication date 2016-05
ISSN 1873-7528
Keyword(s) depression
Th17 cells
autoimmunity
neuroprogression
inflammation
oxidative stress
psychiatry
microbiota
neurotrophins
Science & Technology
Life Sciences & Biomedicine
Behavioral Sciences
Neurosciences
Neurosciences & Neurology
NECROSIS-FACTOR-ALPHA
CENTRAL-NERVOUS-SYSTEM
NITRIC-OXIDE SYNTHASE
EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS
INFLAMMATORY-BOWEL-DISEASE
ROR-GAMMA-T
MEDIATED IMMUNE ACTIVATION
C-REACTIVE PROTEIN
CYTOKINE GM-CSF
QUALITY-OF-LIFE
Summary 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.
Language eng
DOI 10.1016/j.neubiorev.2016.02.002
Field of Research 110319 Psychiatry (incl Psychotherapy)
Socio Economic Objective 920410 Mental Health
HERDC Research category C1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2016 Elsevier Ltd.
Persistent URL http://hdl.handle.net/10536/DRO/DU:30084769

Document type: Journal Article
Collections: Faculty of Health
School of Medicine
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