Department of Psychiatry, Harvard Medical School, Boston, USA.
Laboratory for Psychiatric and Molecular Neuroscience, McLean Hospital, Belmont, USA.
Psychiatry Clin Neurosci. 2019 May;73(5):204-215. doi: 10.1111/pcn.12823. Epub 2019 Mar 6.
Schizophrenia is a chronic and severe psychiatric disorder that has profound impact on an individual's life and on society. Thus, developing more effective therapeutic interventions is essential. Over the past quarter-century, an abundance of evidence from pharmacologic challenges, post-mortem studies, brain imaging, and genetic studies supports the role of glutamatergic dysregulation in the pathophysiology of schizophrenia, and the results of recent randomized clinical trials based on this evidence have yielded promising results. In this article, we review the evidence that alterations in glutamatergic neurotransmission, especially focusing on the N-methyl-d-aspartate receptor (NMDAR) function, may be a critical causative feature of schizophrenia, how this contributes to pathologic circuit function in the brain, and how these insights are revealing whole new avenues for treatment development that could reduce treatment-resistant symptoms, which account for persistent disability.
精神分裂症是一种慢性且严重的精神障碍，对个体的生活和社会都会产生深远的影响。因此，开发更有效的治疗干预措施至关重要。在过去的四分之一个世纪中，大量来自药理学挑战、尸检研究、脑成像和遗传研究的证据支持谷氨酸能失调在精神分裂症病理生理学中的作用，并且基于这些证据的最近的随机临床试验结果也取得了有希望的结果。在本文中，我们回顾了谷氨酸能神经传递改变的证据，特别是聚焦于 N-甲基-D-天冬氨酸受体（NMDAR）功能，这可能是精神分裂症的一个关键致病特征，以及它如何导致大脑病理性回路功能，以及这些见解如何揭示出全新的治疗开发途径，可以减少导致持续残疾的治疗抵抗症状。
