De Maricourt P, Jay T, Goncalvès P, Lôo H, Gaillard R
Service hospitalo-universitaire de santé mentale et de thérapeutique, hôpital Sainte-Anne, université Paris Descartes, centre hospitalier Sainte-Anne, 1, rue Cabanis, 75014 Paris, France; Inserm UMR 894, centre de psychiatrie et neurosciences, université Paris Descartes, Sorbonne Paris Cité, 75014 Paris, France.
Inserm UMR 894, centre de psychiatrie et neurosciences, université Paris Descartes, Sorbonne Paris Cité, 75014 Paris, France.
Encephale. 2014 Feb;40(1):48-55. doi: 10.1016/j.encep.2013.09.002. Epub 2014 Jan 13.
In recent years, discovery of ketamine's fast and powerful antidepressant effects for treatment-resistant depression (TRD) has led to rethinking of the pathophysiology of depression. Numerous studies in humans and animals have focused on mechanisms of action underlying this effect, producing a number of explanatory pathways.
The aim of this article is to summarize the various hypotheses underlying rapid antidepressant action of ketamine and therefore to better understand the mechanisms underlying depression and antidepressant action.
Ketamine unique antidepressant properties have led to many studies on its neurobiological grounds. Intracellular signaling pathways such as mTOR, GSK3 or eEF2 seem to play a key role and are associated with an increased synaptic plasticity. Other hypotheses are discussed such as ketamine effects on neuro-inflammation, the role of anterior cingulate cortex in brain changes induced by ketamine, and the potential benefits of analgesic properties of ketamine in depressive disorders.
Our review highlights the potential role of the glutamatergic system in the pathophysiology and treatment of mood disorders. Understanding which pathways underlie the fast antidepressant effect of ketamine paves the way for the development of new antidepressants.
近年来，氯胺酮对难治性抑郁症（TRD）具有快速且强效的抗抑郁作用这一发现，引发了人们对抑郁症病理生理学的重新思考。众多针对人类和动物的研究聚焦于该作用背后的作用机制，产生了一些解释途径。
本文旨在总结氯胺酮快速抗抑郁作用背后的各种假说，从而更好地理解抑郁症及抗抑郁作用的潜在机制。
氯胺酮独特的抗抑郁特性引发了许多关于其神经生物学基础的研究。细胞内信号通路，如mTOR、GSK3或eEF2，似乎发挥着关键作用，并与突触可塑性增加相关。还讨论了其他假说，如氯胺酮对神经炎症的影响、前扣带回皮质在氯胺酮诱导的大脑变化中的作用，以及氯胺酮镇痛特性在抑郁症中的潜在益处。
我们的综述强调了谷氨酸能系统在情绪障碍病理生理学和治疗中的潜在作用。了解氯胺酮快速抗抑郁作用背后的哪些途径，为新型抗抑郁药的研发铺平了道路。
