Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, United States.
Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, United States.
Psychiatry Res. 2022 Aug;314:114655. doi: 10.1016/j.psychres.2022.114655. Epub 2022 May 28.
In this pilot study (N = 9), we highlight new insights gained on ketamine's mechanism of action where we have mapped biochemical processes that are affected within 40 min of intravenous ketamine exposure. Targeting acylcarnitines, we demonstrated rapid utilization of short-chain acylcarnitines within 40 min of ketamine treatment followed by restoration within 24 h; this change in short chain acylcarnitine with rapid-acting antidepressant treatment is consistent with previous work identifying similar change but at 8-weeks with slower-acting SSRI treatment. Using a non-targeted metabolomics platform, we defined broader effects of ketamine on lipid metabolism and identified changes in triglyceride that correlate with ketamine response. This study provides novel insights into ketamine's action and highlighting a possible role for mitochondrial function and energy metabolism in ketamine's mechanism of action.
在这项初步研究中（N=9），我们重点介绍了氯胺酮作用机制方面的新见解，我们已经绘制了静脉注射氯胺酮暴露 40 分钟内受影响的生化过程图。通过靶向酰基辅酶 A，我们证明了在氯胺酮治疗后 40 分钟内短链酰基辅酶 A的快速利用，随后在 24 小时内恢复；这种快速抗抑郁作用的短链酰基辅酶 A 的变化与先前的工作一致，此前的工作表明，8 周时起效较慢的 SSRI 治疗也会发生类似的变化。本研究使用非靶向代谢组学平台，定义了氯胺酮对脂质代谢的更广泛影响，并确定了与氯胺酮反应相关的甘油三酯变化。这项研究提供了氯胺酮作用机制的新见解，并强调了线粒体功能和能量代谢在氯胺酮作用机制中的可能作用。
