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.
National Institute on Drug Dependence, Peking University, 100191, Beijing, China.
Mol Psychiatry. 2020 Feb;25(2):339-350. doi: 10.1038/s41380-019-0474-5. Epub 2019 Aug 19.
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.
预测抗抑郁治疗反应一直是重性抑郁障碍（MDD）的临床挑战。抑郁的炎症假说表明细胞因子在 MDD 的病理生理学中起关键作用，外周细胞因子水平的改变与抗抑郁治疗结果相关。本研究旨在探讨 MDD 患者治疗前外周细胞因子水平与抗抑郁治疗反应的关系，并评估细胞因子水平的变化是否与抗抑郁治疗反应相关。检索了 PubMed、Embase 和 Web of Science 数据库中所有语言发表的同行评议期刊中的研究，检索时间截至 2018 年 10 月。检索词包括细胞因子、抑郁障碍和抗抑郁药及其同义词。纳入了基于经过验证的抑郁量表报告 MDD 患者治疗前后细胞因子（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 和 Eotaxin-1）水平的病例对照或病例系列研究。在 7408 条记录中，有 44 项研究符合纳入标准。评估了每种细胞因子的标准化均数差值，并进行了随机效应荟萃分析。对接受抗抑郁治疗有反应的 MDD 患者的基线 IL-8 水平低于无反应者（Hedge's g = -0.28；95%CI，-0.43 至-0.13；P = 0.0003；FDR = 0.004）。抗抑郁治疗显著降低了 TNF-α水平（Hedge's g = 0.60；95%CI，0.26-0.94；P = 0.0006；FDR = 0.004），但仅在反应者中，且反应者与无反应者相比，TNF-α水平的降低更显著（P = 0.046）。这些发现表明，外周细胞因子水平的改变与 MDD 的抗抑郁治疗结果相关。需要进一步的研究来阐明异质性的来源，并探讨将炎症细胞因子作为 MDD 药物治疗新的预测标志物的潜力。
