Department of Psychiatry, Chang Gung Memorial Hospital, Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Pharmacol Biochem Behav. 2012 Feb;100(4):665-77. doi: 10.1016/j.pbb.2011.03.023. Epub 2011 Apr 1.
Glutamatergic neurotransmission, particularly through the N-methyl-d-aspartate (NMDA) receptor, has drawn attention for its role in the pathophysiology of schizophrenia. This paper reviews the neurodevelopmental origin and genetic susceptibility of schizophrenia relevant to NMDA neurotransmission, and discusses the relationship between NMDA hypofunction and different domains of symptom in schizophrenia as well as putative treatment modality for the disorder. A series of clinical trials and a meta-analysis which compared currently available NMDA-enhancing agents suggests that glycine, d-serine, and sarcosine are more efficacious than d-cycloserine in improving the overall psychopathology of schizophrenia without side effect or safety concern. In addition, enhancing glutamatergic neurotransmission via activating the AMPA receptor, metabotropic glutamate receptor or inhibition of d-amino acid oxidase (DAO) is also reviewed. More studies are needed to determine the NMDA vulnerability in schizophrenia and to confirm the long-term efficacy, functional outcome, and safety of these NMDA-enhancing agents in schizophrenic patients, particularly those with refractory negative and cognitive symptoms, or serious adverse effects while taking the existing antipsychotic agents.
谷氨酸能神经传递，特别是通过 N-甲基-D-天冬氨酸（NMDA）受体，因其在精神分裂症的病理生理学中的作用而引起关注。本文综述了与 NMDA 神经传递有关的精神分裂症的神经发育起源和遗传易感性，并讨论了 NMDA 功能低下与精神分裂症不同症状领域之间的关系，以及该疾病的潜在治疗方式。一系列临床试验和荟萃分析比较了目前可用的 NMDA 增强剂，表明甘氨酸、D-丝氨酸和肌氨酸在改善精神分裂症的整体精神病理学方面比 D-环丝氨酸更有效，且没有副作用或安全性问题。此外，还综述了通过激活 AMPA 受体、代谢型谷氨酸受体或抑制 D-氨基酸氧化酶（DAO）来增强谷氨酸能神经传递。需要更多的研究来确定精神分裂症中的 NMDA 易感性，并确认这些 NMDA 增强剂在精神分裂症患者中的长期疗效、功能结果和安全性，特别是那些有难治性阴性和认知症状或在服用现有抗精神病药物时出现严重不良反应的患者。
