NMDA 受体与精神分裂症：简要的历史。
NMDA receptor and schizophrenia: a brief history.
机构信息
Department of Psychiatry and Neuroscience, Harvard Medical School, McLean Hospital, Belmont, MA, USA.
出版信息
Schizophr Bull. 2012 Sep;38(5):920-6. doi: 10.1093/schbul/sbs076.
Abstract
Although glutamate was first hypothesized to be involved in the pathophysiology of schizophrenia in the 1980s, it was the demonstration that N-methyl-D-aspartate (NMDA) receptor antagonists, the dissociative anesthetics, could replicate the full range of psychotic, negative, cognitive, and physiologic features of schizophrenia in normal subjects that placed the "NMDA receptor hypofunction hypothesis" on firm footing. Additional support came from the demonstration that a variety of agents that enhanced NMDA receptor function at the glycine modulatory site significantly reduced negative symptoms and variably improved cognition in patients with schizophrenia receiving antipsychotic drugs. Finally, persistent blockade of NMDA receptors recreates in experimental animals the critical pathologic features of schizophrenia including downregulation of parvalbumin-positive cortical GABAergic neurons, pyramidal neuron dendritic dysgenesis, and reduced spine density.
摘要
虽然谷氨酸在 20 世纪 80 年代就被首次假设与精神分裂症的病理生理学有关，但正是 NMDA 受体拮抗剂（分离麻醉剂）的证明，能够在正常受试者中复制精神分裂症的全部精神病、阴性、认知和生理特征，这使得“NMDA 受体功能低下假说”有了坚实的基础。另外的支持来自于这样的证明，即各种增强 NMDA 受体在甘氨酸调节位点的功能的药物显著减少了接受抗精神病药物治疗的精神分裂症患者的阴性症状，并不同程度地改善了认知功能。最后，NMDA 受体的持续阻断在实验动物中重现了精神分裂症的关键病理特征，包括下调 GABA 能神经元的 PV 阳性皮层、锥体神经元树突发育不良和减少棘突密度。
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