Department of Psychiatry, Yale University School of Medicine, 34 Park Street, New Haven, CT 06508, USA.
Science. 2012 Oct 5;338(6103):68-72. doi: 10.1126/science.1222939.
Basic and clinical studies demonstrate that depression is associated with reduced size of brain regions that regulate mood and cognition, including the prefrontal cortex and the hippocampus, and decreased neuronal synapses in these areas. Antidepressants can block or reverse these neuronal deficits, although typical antidepressants have limited efficacy and delayed response times of weeks to months. A notable recent discovery shows that ketamine, a N-methyl-D-aspartate receptor antagonist, produces rapid (within hours) antidepressant responses in patients who are resistant to typical antidepressants. Basic studies show that ketamine rapidly induces synaptogenesis and reverses the synaptic deficits caused by chronic stress. These findings highlight the central importance of homeostatic control of mood circuit connections and form the basis of a synaptogenic hypothesis of depression and treatment response.
基础和临床研究表明，抑郁症与调节情绪和认知的大脑区域（包括前额叶皮层和海马体）缩小以及这些区域的神经元突触减少有关。抗抑郁药可以阻断或逆转这些神经元缺陷，尽管典型的抗抑郁药疗效有限，且反应时间需要数周至数月。最近的一项重要发现表明，N-甲基-D-天冬氨酸受体拮抗剂氯胺酮可在对典型抗抑郁药有抵抗的患者中产生快速（数小时内）的抗抑郁反应。基础研究表明，氯胺酮可迅速诱导突触发生，并逆转慢性应激引起的突触缺陷。这些发现突出了情绪回路连接的稳态控制的重要性，并为抑郁症和治疗反应的突触发生假说奠定了基础。
