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

Molecular Psychiatry volume 25, pages 339–350 (2020)Cite this article

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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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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.

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  1. These authors contributed equally: Jia Jia Liu, Ya Bin Wei

Authors and Affiliations

  1. Institute of Mental Health, National Clinical Research Center for Mental Disorders, Key Laboratory of Mental Health and Peking University Sixth Hospital, Peking University, 100191, Beijing, China

    Jia Jia Liu, Suhua Chang, Le Shi, Jianyu Que & Lin Lu

  2. National Institute on Drug Dependence, Peking University, 100191, Beijing, China

    Jia Jia Liu, Yanping Bao & Lin Lu

  3. Center for Molecular Medicine, Karolinska University Hospital, 17176, Stockholm, Sweden

    Ya Bin Wei

  4. Department of Molecular Medicine and Surgery, Karolinska Institutet, 17176, Stockholm, Sweden

    Ya Bin Wei

  5. Department of Psychiatry, University of California San Diego, La Jolla, CA, 92093, USA

    Ya Bin Wei & John R. Kelsoe

  6. Affective Disorders Research Group, Centre for Affective Disorders, Psychological Medicine, Institute of Psychiatry, King’s College London, London, UK

    Rebecca Strawbridge

  7. Department of Psychiatry, Texas Tech University Health Science Center, El Paso, TX, 79905, USA

    Bharathi S. Gadad

  8. Center for Depression Research and Clinical Care, Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, 75235, USA

    Bharathi S. Gadad & Madhukar H. Trivedi

  9. Department of Psychiatry, VA San Diego Healthcare System, La Jolla, CA, 92093, USA

    John R. Kelsoe

  10. Institute for Genomic Medicine, University of California San Diego, La Jolla, CA, 92093, USA

    John R. Kelsoe

  11. Peking-Tsinghua Center for Life Sciences and PKU-IDG/McGovern Institute for Brain Research, Peking University, 100871, Beijing, China

    Lin Lu

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Liu, J.J., Wei, Y.B., Strawbridge, R. et al. Peripheral cytokine levels and response to antidepressant treatment in depression: a systematic review and meta-analysis. Mol Psychiatry 25, 339–350 (2020). https://doi.org/10.1038/s41380-019-0474-5

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