Duman Ronald S
Laboratory of Molecular Psychiatry, Department of Psychiatry, Yale University School of Medicine, New Haven Connecticut.
Depress Anxiety. 2014 Apr;31(4):291-6. doi: 10.1002/da.22227. Epub 2014 Mar 10.
Stress and depression are associated with atrophy and loss of neurons in limbic and cortical brain regions that could contribute to the symptoms of depression. Typical monoamine reuptake inhibitor antidepressants have only modest efficacy and require long-term treatment, and are only weakly effective in blocking or reversing these structural changes caused by stress. Recent findings demonstrate that ketamine, an NMDA receptor antagonist, produces rapid antidepressant actions in difficult to treat depressed patients. In addition, preclinical studies demonstrate that ketamine rapidly increases synaptic connections in the prefrontal cortex by increasing glutamate signaling and activation of pathways that control the synthesis of synaptic proteins. Moreover, ketamine rapidly reverses the synaptic deficits caused by exposure to chronic stress in rodent models. Studies of the signaling mechanisms underlying the actions of ketamine have provided novel approaches and targets for new rapid acting antidepressants with decreased side effects, as well as a better understanding of the neurobiology of stress, depression, and treatment response.
压力和抑郁与边缘脑区和皮质脑区神经元的萎缩及丧失有关，这可能导致抑郁症状。典型的单胺再摄取抑制剂抗抑郁药疗效有限，需要长期治疗，且在阻断或逆转由压力引起的这些结构变化方面效果不佳。最近的研究结果表明，NMDA受体拮抗剂氯胺酮在难治性抑郁症患者中能产生快速的抗抑郁作用。此外，临床前研究表明，氯胺酮通过增加谷氨酸信号传导和激活控制突触蛋白合成的途径，迅速增加前额叶皮质的突触连接。此外，氯胺酮能迅速逆转啮齿动物模型中因长期应激而导致的突触缺陷。对氯胺酮作用的信号传导机制的研究为副作用减少的新型速效抗抑郁药提供了新的方法和靶点，也有助于更好地理解压力、抑郁和治疗反应的神经生物学机制。
