Peripheral cytokine levels and response to antidepressant treatment in depression: a systematic review and meta-analysis

Jia Jia Liu, Ya Bin Wei, Rebecca Strawbridge, Yanping Bao, Suhua Chang, Le Shi, Jianyu Que, Bharathi Gadad, Madhukar H Trivedi, John R. Kelsoe, Lin Lu

Research output: Contribution to journalReview article

1 Citation (Scopus)

Abstract

Predicting antidepressant treatment response has been a clinical challenge for major depressive disorder (MDD). The inflammation hypothesis of depression suggests that cytokines play a key role in the pathophysiology of MDD and alterations in peripheral cytokine levels are associated with antidepressant treatment outcome. Present meta-analysis aimed to examine the association between baseline peripheral cytokine levels and the response to antidepressant treatment and to evaluate whether changes of cytokine levels were associated with the response to antidepressant treatment in patients with MDD. Human-based studies published in any language in peer-reviewed journals were systematically searched from the PubMed, Embase and Web of Science databases, from inception up to October 2018. The search terms included cytokine, depressive disorder and antidepressant and their synonyms. Case–control or case–case studies reporting on levels of IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, CRP, TNF-α, IFN-γ, GM-CSF, MIP-1α, and Eotaxin-1 in patients with MDD based on validated depression scales both before and after antidepressant treatment were included. Of 7408 identified records, 44 studies met inclusion. Standardized mean differences in each cytokine were evaluated, and random-effects meta-analyses were performed. MDD patients who responded to antidepressant treatment had lower baseline IL-8 levels than the nonresponders (Hedge’s g = −0.28; 95%CI, −0.43 to −0.13; P = 0.0003; FDR = 0.004). Antidepressant treatment significantly decreased levels of TNF-α (Hedge’s g = 0.60; 95%CI, 0.26–0.94; P = 0.0006; FDR = 0.004) only in responders, and responders showed significantly more decreased TNF-α levels compared with nonresponders (P = 0.046). These findings suggested that alterations in peripheral cytokine levels were associated with antidepressant treatment outcomes in MDD. Further investigations are warranted to elucidate sources of heterogeneity and examine the potentiality of using inflammatory cytokines as novel predictive markers for the pharmacological treatment of MDD.

Original languageEnglish (US)
JournalMolecular Psychiatry
DOIs
StateAccepted/In press - Jan 1 2019

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Antidepressive Agents
Meta-Analysis
Major Depressive Disorder
Depression
Cytokines
Therapeutics
Interleukin-8
Chemokine CCL11
Macrophage Colony-Stimulating Factor
Interleukin-5
Interleukin-12
Granulocyte-Macrophage Colony-Stimulating Factor
Depressive Disorder
Interleukin-1
PubMed
Interleukin-4
Interleukin-10
Interleukin-2
Interleukin-6
Language

ASJC Scopus subject areas

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

Cite this

Peripheral cytokine levels and response to antidepressant treatment in depression : a systematic review and meta-analysis. / Liu, Jia Jia; Wei, Ya Bin; Strawbridge, Rebecca; Bao, Yanping; Chang, Suhua; Shi, Le; Que, Jianyu; Gadad, Bharathi; Trivedi, Madhukar H; Kelsoe, John R.; Lu, Lin.

In: Molecular Psychiatry, 01.01.2019.

Research output: Contribution to journalReview article

Liu, Jia Jia ; Wei, Ya Bin ; Strawbridge, Rebecca ; Bao, Yanping ; Chang, Suhua ; Shi, Le ; Que, Jianyu ; Gadad, Bharathi ; Trivedi, Madhukar H ; Kelsoe, John R. ; Lu, Lin. / Peripheral cytokine levels and response to antidepressant treatment in depression : a systematic review and meta-analysis. In: Molecular Psychiatry. 2019.
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abstract = "Predicting antidepressant treatment response has been a clinical challenge for major depressive disorder (MDD). The inflammation hypothesis of depression suggests that cytokines play a key role in the pathophysiology of MDD and alterations in peripheral cytokine levels are associated with antidepressant treatment outcome. Present meta-analysis aimed to examine the association between baseline peripheral cytokine levels and the response to antidepressant treatment and to evaluate whether changes of cytokine levels were associated with the response to antidepressant treatment in patients with MDD. Human-based studies published in any language in peer-reviewed journals were systematically searched from the PubMed, Embase and Web of Science databases, from inception up to October 2018. The search terms included cytokine, depressive disorder and antidepressant and their synonyms. Case–control or case–case studies reporting on levels of IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, CRP, TNF-α, IFN-γ, GM-CSF, MIP-1α, and Eotaxin-1 in patients with MDD based on validated depression scales both before and after antidepressant treatment were included. Of 7408 identified records, 44 studies met inclusion. Standardized mean differences in each cytokine were evaluated, and random-effects meta-analyses were performed. MDD patients who responded to antidepressant treatment had lower baseline IL-8 levels than the nonresponders (Hedge’s g = −0.28; 95{\%}CI, −0.43 to −0.13; P = 0.0003; FDR = 0.004). Antidepressant treatment significantly decreased levels of TNF-α (Hedge’s g = 0.60; 95{\%}CI, 0.26–0.94; P = 0.0006; FDR = 0.004) only in responders, and responders showed significantly more decreased TNF-α levels compared with nonresponders (P = 0.046). These findings suggested that alterations in peripheral cytokine levels were associated with antidepressant treatment outcomes in MDD. Further investigations are warranted to elucidate sources of heterogeneity and examine the potentiality of using inflammatory cytokines as novel predictive markers for the pharmacological treatment of MDD.",
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AU - Shi, Le

AU - Que, Jianyu

AU - Gadad, Bharathi

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