Wu Qiongqiong, Huang Jing, Wu Renrong
Department of Psychiatry, National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, China.
Front Neurosci. 2021 Apr 12;15:641047. doi: 10.3389/fnins.2021.641047. eCollection 2021.
Treatments for negative symptoms and cognitive dysfunction in schizophrenia remain issues that psychiatrists around the world are trying to solve. Their mechanisms may be associated with N-methyl-D-aspartate receptors (NMDARs). The NMDAR hypofunction hypothesis for schizophrenia was brought to the fore mainly based on the clinical effects of NMDAR antagonists and anti-NMDAR encephalitis pathology. Drugs targeted at augmenting NMDAR function in the brain seem to be promising in improving negative symptoms and cognitive dysfunction in patients with schizophrenia. In this review, we list NMDAR-targeted drugs and report on related clinical studies. We then summarize their effects on negative symptoms and cognitive dysfunction and analyze the unsatisfactory outcomes of these clinical studies according to the improved glutamate hypothesis that has been revealed in animal models. We aimed to provide perspectives for scientists who sought therapeutic strategies for negative symptoms and cognitive dysfunction in schizophrenia based on the NMDAR hypofunction hypothesis.
精神分裂症阴性症状和认知功能障碍的治疗仍然是世界各地精神科医生试图解决的问题。其机制可能与N-甲基-D-天冬氨酸受体（NMDARs）有关。精神分裂症的NMDAR功能低下假说主要基于NMDAR拮抗剂的临床效果和抗NMDAR脑炎病理学而受到关注。旨在增强大脑中NMDAR功能的药物似乎有望改善精神分裂症患者的阴性症状和认知功能障碍。在这篇综述中，我们列出了针对NMDAR的药物并报告了相关临床研究。然后，我们总结了它们对阴性症状和认知功能障碍的影响，并根据动物模型中揭示的改良谷氨酸假说分析了这些临床研究不尽人意的结果。我们旨在为基于NMDAR功能低下假说寻求精神分裂症阴性症状和认知功能障碍治疗策略的科学家提供观点。
