How antidepressant drugs act: A primer on neuroplasticity as the eventual mediator of antidepressant efficacy.
How antidepressant drugs act: A primer on neuroplasticity as the eventual mediator of antidepressant efficacy.
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DOI：
10.4103/0019-5545.74318
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发表时间：
2010-10
影响因子：
3.1
通讯作者：
Rao NS
中科院分区：
文献类型：
--
作者：
Andrade C;Rao NS
抑郁症通常被认为是一种化学失衡的状态，抗抑郁药被认为是通过增加单胺能神经传递来起作用的。这些观点目前被认为过于简单化。本文综述了应激、抑郁和抗抑郁药物治疗的神经组织学机制的动物和人类文献。病理性应激和抑郁与诸如树突棘的丧失、树突树的萎缩以及海马和前额皮质突触的丧失等变化有关。神经胶质细胞也在减少。在极端情况下可能发生细胞凋亡。相反，杏仁核的树突树突和突触发生增加。抗抑郁治疗可以防止甚至逆转一些压力引起的神经组织学变化，但不是全部。病理性应激导致异常的神经可塑性反应，其特征是杏仁核活动异常增加，海马、前额叶皮层和下游结构功能受损。这种异常的神经可塑性反应直接解释了大多数抑郁症的临床症状。抗抑郁治疗可防止应激诱导的病理神经组织学和神经认知改变。抗抑郁药物治疗还可以恢复应激生物体的功能性神经可塑性，因此，据推测，可以通过学习和记忆机制促进重新适应。因此，压力-抑郁综合征和抗抑郁药物治疗的治疗和预防效果可以通过一个硬连线类比来解释。在这种情况下，谷氨酸是一种重要的神经递质。
Depression is conventionally viewed as a state of chemical imbalance, and antidepressants are suggested to act through increasing monoaminergic neurotransmission. These views are currently considered simplistic. This article examines the animal and human literature on the neurohistological mechanisms underlying stress, depression and antidepressant treatment. Pathological stress and depression are associated with changes such as loss of dendritic spines, shrinkage of the dendritic tree and loss of synapses in the hippocampus and prefrontal cortex. There is also a decrease in glia. Apoptosis may occur under extreme circumstances. In contrast, there is increased dendritic arborization and synaptogenesis in the amygdala. Antidepressant treatment protects against and even reverses some but not all of these stress-induced neurohistological changes. Pathological stress results in an aberrant neuroplasticity response characterized by abnormally increased activity in the amygdala and by impaired functioning of the hippocampus, prefrontal cortex and downstream structures. This aberrant neuroplasticity response directly explains most of the clinical symptoms of depression. Antidepressant treatment protects against stress-induced pathoplastic neurohistological and neurocognitive changes. Antidepressant treatment also restores functional neuroplasticity in stressed organisms and, thereby, presumably, facilitates re-adaptation through learning and memory mechanisms. Thus, the stress–depression syndrome and the therapeutic and prophylactic efficacy of antidepressant treatments can be explained through a hardwiring analogy. In this context, glutamate is an important neurotransmitter.