TY - JOUR
T1 - Peripheral cytokine levels and response to antidepressant treatment in depression
T2 - a systematic review and meta-analysis
AU - Liu, Jia Jia
AU - Wei, Ya Bin
AU - Strawbridge, Rebecca
AU - Bao, Yanping
AU - Chang, Suhua
AU - Shi, Le
AU - Que, Jianyu
AU - Gadad, Bharathi S.
AU - Trivedi, Madhukar H.
AU - Kelsoe, John R.
AU - Lu, Lin
N1 - Funding Information:
Acknowledgements JJL was supported by the National Natural Science Foundation of China (No. 81801344), Postdoctoral Fellowship of Peking-Tsinghua Center for Life Sciences and China Postdoctoral Science Foundation (No. 189826). YBW was supported by the Swedish Research Council (Reg no. 2015-06372). RS was supported by the UK’s National Institute for Health Research (NIHR) Biomedical Research Centre (BRC) at South London and Maudsley NHS Foundation Trust (SLaM) and King’s College London (KCL). JRK was supported by grants from the NIMH (U01 MH92758) and the Department of Veterans Affairs. LL was supported by the grants from the National Natural Science Foundation of China (Nos. 81761128036 and 81821092), and 973 Program (Nos. 2015CB856400 and 2015CB553503). We thank all the authors who contributed their data to this study. We also appreciate Prof. Peng Guan and Naixue Cui for their suggestions on improving the paper.
PY - 2020/2/1
Y1 - 2020/2/1
N2 - 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.
AB - 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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U2 - 10.1038/s41380-019-0474-5
DO - 10.1038/s41380-019-0474-5
M3 - Review article
C2 - 31427752
AN - SCOPUS:85071117843
VL - 25
SP - 339
EP - 350
JO - Molecular Psychiatry
JF - Molecular Psychiatry
SN - 1359-4184
IS - 2
ER -