Cumulative meta-analysis of interleukins 6 and 1β, tumour necrosis factor α and C-reactive protein in patients with major depressive disorder.
Cumulative meta-analysis of interleukins 6 and 1β, tumour necrosis factor α and C-reactive protein in patients with major depressive disorder.
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DOI：
10.1016/j.bbi.2015.06.001
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发表时间：
2015-10
期刊：
影响因子：
--
通讯作者：
Kivimäki M
中科院分区：
文献类型：
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作者：
Haapakoski R;Mathieu J;Ebmeier KP;Alenius H;Kivimäki M
这项荟萃分析证实了白细胞介素 - 6（IL - 6）、C反应蛋白（CRP）与重度抑郁症之间存在紧密联系。
肿瘤坏死因子 - α（TNF - α）和白细胞介素 - 1β（IL - 1β）在重度抑郁症中的作用仍不确定。
需要对IL - 6和CRP进行进一步的机制研究和免疫治疗研究。
累积荟萃分析用于评估还需要多少进一步的研究来证实或反驳一个假设。我们使用这种方法来评估重度抑郁症患者全身炎症的观察性证据。2014年5月，我们在PubMed、Embase和PsychInfo数据库的文献检索中确定了58项关于四种常见炎症标志物的研究。来自最早的8项研究的汇总数据已经显示白细胞介素 - 6浓度与重度抑郁症之间存在关联；另外23项近期研究证实了这一发现（效应量d = 0.54，p < 0.0001）。在14项研究之后，注意到C反应蛋白水平与重度抑郁症之间存在显著关联，并且在增加6项研究后这一结果没有改变（d = 0.47，p < 0.0001）。对于这两种炎症标志物，研究特定估计值存在中等程度的异质性，亚组差异较小，发表偏倚似乎不太可能是这些发现的原因。仅包括高质量研究和未服用抗抑郁药物的受试者的敏感性分析进一步验证了这些关联。虽然肿瘤坏死因子 - α水平与重度抑郁症之间存在联系（d = 0.40，p = 0.002），但由于研究特定估计值存在广泛的异质性以及亚组之间的不一致，累积效应仍不确定。没有发现白细胞介素 - 1β水平与重度抑郁症之间存在关联的证据（d = - 0.05，p = 0.86）。总之，这项累积荟萃分析证实，与非抑郁对照组相比，重度抑郁症患者的白细胞介素 - 6和C反应蛋白平均水平更高。没有观察到肿瘤坏死因子 - α、白细胞介素 - 1β与重度抑郁症之间存在一致的关联。未来的研究应阐明所涉及的具体免疫机制，并继续在重度抑郁症患者中测试抗炎疗法。
This meta-analysis confirms a robust link between IL-6, CRP and major depression. The role of TNF-α and IL-1β in major depression remains uncertain. Further mechanistic and immunotherapeutic studies on IL-6 and CRP are needed. Cumulative meta-analyses are used to evaluate the extent to which further studies are needed to confirm or refute a hypothesis. We used this approach to assess observational evidence on systemic inflammation in individuals with major depressive disorder. We identified 58 studies of four common inflammatory markers in a literature search of PubMed, Embase and PsychInfo databases in May 2014. Pooled data from the earliest eight studies already showed an association between interleukin-6 concentrations and major depression; 23 more recent studies confirmed this finding (d = 0.54, p < 0.0001). A significant association between C-reactive protein levels and major depression was noted after 14 studies and this did not change after addition of six more studies (d = 0.47, p < 0.0001). For these two inflammatory markers, there was moderate heterogeneity in study-specific estimates, subgroup differences were small, and publication bias appeared to be an unlikely explanation for the findings. Sensitivity analyses including only high-quality studies and subjects free of antidepressant medication further verified the associations. While there was a link between tumour necrosis factor-α levels and major depression (d = 0.40, p = 0.002), the cumulative effect remained uncertain due to the extensive heterogeneity in study-specific estimates and inconsistencies between subgroups. No evidence was found for the association between interleukin-1β levels and major depression (d = −0.05, p = 0.86). In conclusion, this cumulative meta-analysis confirmed higher mean levels of interleukin-6 and C-reactive protein in patients with major depression compared to non-depressed controls. No consistent association between tumour necrosis factor-α, interleukin-1β and major depression was observed. Future studies should clarify the specific immune mechanisms involved as well as continue testing anti-inflammatory therapies in patients suffering from major depression.