The role of glutamate in mood disorders: results from the ketamine in major depression study and the presumed cellular mechanism underlying its antidepressant effects.
The role of glutamate in mood disorders: results from the ketamine in major depression study and the presumed cellular mechanism underlying its antidepressant effects.
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DOI：
10.1007/s11920-007-0063-1
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发表时间：
2007-12-01
影响因子：
6.7
通讯作者：
Zarate, Carlos A Jr
中科院分区：
文献类型：
--
作者：
Maeng, Sungho;Zarate, Carlos A Jr
在本文中，我们首先回顾了一项研究，该研究表明 N-甲基-D-天冬氨酸 (NMDA) 受体拮抗剂氯胺酮对难治性重度抑郁症患者可产生快速、强劲且相对持续的抗抑郁作用。然后我们讨论了我们的假设，即单胺能抗抑郁药和氯胺酮的治疗作用可能是通过增加关键神经元回路中 AMPA 至 NMDA 谷氨酸受体的吞吐量来介导的。我们假设氯胺酮直接介导这种吞吐量，而单胺能抗抑郁药则间接且逐渐发挥作用。这可以部分解释传统抗抑郁药起效延迟数周至数月的现象。
In this article, we first review a study showing that the N-methyl-D-aspartate (NMDA) receptor antagonist ketamine leads to rapid, robust, and relatively sustained antidepressant effects in patients with treatment-resistant major depression. We then discuss our hypothesis that the therapeutic effects of monoaminergic antidepressants and ketamine may be mediated by increased AMPA-to-NMDA glutamate receptor throughput in critical neuronal circuits. We hypothesize that ketamine directly mediates this throughput, whereas monoaminergic antidepressants work indirectly and gradually; this may explain, in part, the lag of onset of several weeks to months that is observed with traditional antidepressants.