Department of Psychiatry, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, 80045, CO, USA.
Neuropsychopharmacology. 2023 Jan;48(1):90-103. doi: 10.1038/s41386-022-01422-1. Epub 2022 Sep 3.
What changes in brain function cause the debilitating symptoms of depression? Can we use the answers to this question to invent more effective, faster acting antidepressant drug therapies? This review provides an overview and update of the converging human and preclinical evidence supporting the hypothesis that changes in the function of excitatory synapses impair the function of the circuits they are embedded in to give rise to the pathological changes in mood, hedonic state, and thought processes that characterize depression. The review also highlights complementary human and preclinical findings that classical and novel antidepressant drugs relieve the symptoms of depression by restoring the functions of these same synapses and circuits. These findings offer a useful path forward for designing better antidepressant compounds.
大脑功能的哪些变化导致了抑郁症的衰弱症状？我们能否利用这个问题的答案来发明更有效、作用更快的抗抑郁药物治疗方法？本文综述了支持这样一个假设的汇聚的人类和临床前证据，即兴奋性突触功能的改变损害了它们所嵌入的回路的功能，从而导致了抑郁症的情绪、快感状态和思维过程的病理性变化。该综述还强调了人类和临床前的补充发现，即经典和新型抗抑郁药物通过恢复这些相同的突触和回路的功能来缓解抑郁症的症状。这些发现为设计更好的抗抑郁化合物提供了一条有用的途径。
