Several pro-inflammatory cytokines have been implicated in depression and in antidepressant response. This exploratory analysis assessed: 1) the extent to which baseline cytokine levels predicted positive antidepressant response to ketamine; 2) whether ketamine responders experienced acute changes in cytokine levels not observed in non-responders; and 3) whether ketamine lowered levels of pro-inflammatory cytokines, analogous to the impact of other antidepressants. Data from double-blind, placebo-controlled studies of patients with major depressive disorder (MDD) or bipolar disorder (BD) who received a single infusion of sub-anesthetic dose ketamine were used (N = 80). Plasma levels of the eight cytokines were measured at baseline and at 230 min, 1 day, and 3 days post-ketamine. A significant positive correlation was observed between sTNFR1 and severity of depression at baseline. Cytokine changes did not correlate with changes in mood nor predict mood changes associated with ketamine administration. Ketamine significantly increased IL-6 levels and significantly decreased sTNFR1 levels. IL-6 and TNF-α levels were also significantly higher-and sTNFR1 levels were significantly lower-in BD compared to MDD subjects. The functional significance of this difference is unknown. Changes in cytokine levels post-ketamine were not related to antidepressant response, suggesting they are not a primary mechanism involved in ketamine's acute antidepressant effects. Taken together, the results suggest that further study of cytokine levels is warranted to assess their potential role as a surrogate outcome in the rapid antidepressant response paradigm.

中文翻译：

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在难治性抑郁症中，细胞因子水平的变化与氯胺酮的快速抗抑郁反应无关。

几种促炎细胞因子与抑郁和抗抑郁反应有关。该探索性分析评估：1）基线细胞因子水平预测对氯胺酮阳性抗抑郁药反应的程度；2）氯胺酮反应者是否经历了在非反应者中未观察到的细胞因子水平的急性变化；3）氯胺酮是否降低了促炎细胞因子的水平，类似于其他抗抑郁药的影响。使用来自接受单次麻醉剂量氯胺酮输注的重度抑郁症（MDD）或双相情感障碍（BD）患者的双盲，安慰剂对照研究的数据（N = 80）。在氯胺酮后的基线和230分钟，1天和3天测量了这8种细胞因子的血浆水平。在基线时，sTNFR1与抑郁严重程度之间存在显着的正相关。细胞因子的变化与情绪变化没有关联，也没有预测与氯胺酮给药有关的情绪变化。氯胺酮显着增加IL-6水平，并显着降低sTNFR1水平。与MDD受试者相比，BD的IL-6和TNF-α水平也显着升高，而sTNFR1水平显着降低。这种差异的功能意义尚不清楚。氯胺酮后细胞因子水平的变化与抗抑郁药的反应无关，表明它们不是氯胺酮急性抗抑郁药作用的主要机制。在一起