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

Research output: Contribution to journalReview article

75 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)4195-4206
Number of pages12
JournalMolecular Neurobiology
Volume55
Issue number5
DOIs
StatePublished - May 1 2018

Fingerprint

Major Depressive Disorder
Chemokines
Antidepressive Agents
Meta-Analysis
Cytokines
Interleukin-1beta
Interleukin-6
Chemokine CCL2
Interleukin-10
Therapeutics
Tumor Necrosis Factor-alpha
Inflammation
Interleukin-7
Interleukin-1 Receptors
Interleukin-13
Interleukin-17
Interleukin-2 Receptors
Interleukin-5
Interleukin-8
PubMed

Keywords

  • Antidepressant
  • Chemokines
  • Cytokines
  • Depression
  • Inflammation
  • Meta-analysis

ASJC Scopus subject areas

  • Neuroscience (miscellaneous)
  • Neurology
  • Cellular and Molecular Neuroscience

Cite this

Peripheral Alterations in Cytokine and Chemokine Levels After Antidepressant Drug Treatment for Major Depressive Disorder : Systematic Review and Meta-Analysis. / Köhler, Cristiano A.; Freitas, Thiago H.; Stubbs, Brendon; Maes, Michael; Solmi, Marco; Veronese, Nicola; de Andrade, Nayanna Q.; Morris, Gerwyn; Fernandes, Brisa S.; Brunoni, André R.; Herrmann, Nathan; Raison, Charles L.; Miller, Brian J; Lanctôt, Krista L.; Carvalho, André F.

In: Molecular Neurobiology, Vol. 55, No. 5, 01.05.2018, p. 4195-4206.

Research output: Contribution to journalReview article

Köhler, CA, Freitas, TH, Stubbs, B, Maes, M, Solmi, M, Veronese, N, de Andrade, NQ, Morris, G, Fernandes, BS, Brunoni, AR, Herrmann, N, Raison, CL, Miller, BJ, Lanctôt, KL & Carvalho, AF 2018, 'Peripheral Alterations in Cytokine and Chemokine Levels After Antidepressant Drug Treatment for Major Depressive Disorder: Systematic Review and Meta-Analysis', Molecular Neurobiology, vol. 55, no. 5, pp. 4195-4206. https://doi.org/10.1007/s12035-017-0632-1
Köhler, Cristiano A. ; Freitas, Thiago H. ; Stubbs, Brendon ; Maes, Michael ; Solmi, Marco ; Veronese, Nicola ; de Andrade, Nayanna Q. ; Morris, Gerwyn ; Fernandes, Brisa S. ; Brunoni, André R. ; Herrmann, Nathan ; Raison, Charles L. ; Miller, Brian J ; Lanctôt, Krista L. ; Carvalho, André F. / Peripheral Alterations in Cytokine and Chemokine Levels After Antidepressant Drug Treatment for Major Depressive Disorder : Systematic Review and Meta-Analysis. In: Molecular Neurobiology. 2018 ; Vol. 55, No. 5. pp. 4195-4206.
@article{5295491d11ee46b48bea9f5706a0b777,
title = "Peripheral Alterations in Cytokine and Chemokine Levels After Antidepressant Drug Treatment for Major Depressive Disorder: Systematic Review and Meta-Analysis",
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.",
keywords = "Antidepressant, Chemokines, Cytokines, Depression, Inflammation, Meta-analysis",
author = "K{\"o}hler, {Cristiano A.} and Freitas, {Thiago H.} and Brendon Stubbs and Michael Maes and Marco Solmi and Nicola Veronese and {de Andrade}, {Nayanna Q.} and Gerwyn Morris and Fernandes, {Brisa S.} and Brunoni, {Andr{\'e} R.} and Nathan Herrmann and Raison, {Charles L.} and Miller, {Brian J} and Lanct{\^o}t, {Krista L.} and Carvalho, {Andr{\'e} F.}",
year = "2018",
month = "5",
day = "1",
doi = "10.1007/s12035-017-0632-1",
language = "English (US)",
volume = "55",
pages = "4195--4206",
journal = "Molecular Neurobiology",
issn = "0893-7648",
publisher = "Humana Press",
number = "5",

}

TY - JOUR

T1 - Peripheral Alterations in Cytokine and Chemokine Levels After Antidepressant Drug Treatment for Major Depressive Disorder

T2 - Systematic Review and Meta-Analysis

AU - Köhler, Cristiano A.

AU - Freitas, Thiago H.

AU - Stubbs, Brendon

AU - Maes, Michael

AU - Solmi, Marco

AU - Veronese, Nicola

AU - de Andrade, Nayanna Q.

AU - Morris, Gerwyn

AU - Fernandes, Brisa S.

AU - Brunoni, André R.

AU - Herrmann, Nathan

AU - Raison, Charles L.

AU - Miller, Brian J

AU - Lanctôt, Krista L.

AU - Carvalho, André F.

PY - 2018/5/1

Y1 - 2018/5/1

N2 - 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.

AB - 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.

KW - Antidepressant

KW - Chemokines

KW - Cytokines

KW - Depression

KW - Inflammation

KW - Meta-analysis

UR - http://www.scopus.com/inward/record.url?scp=85020741434&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85020741434&partnerID=8YFLogxK

U2 - 10.1007/s12035-017-0632-1

DO - 10.1007/s12035-017-0632-1

M3 - Review article

C2 - 28612257

AN - SCOPUS:85020741434

VL - 55

SP - 4195

EP - 4206

JO - Molecular Neurobiology

JF - Molecular Neurobiology

SN - 0893-7648

IS - 5

ER -