Stone James M, Morrison Paul D, Pilowsky Lyn S
King's College London Institute of Psychiatry, London, UK.
J Psychopharmacol. 2007 Jun;21(4):440-52. doi: 10.1177/0269881106073126. Epub 2007 Jan 26.
The dopamine hypothesis of schizophrenia is the principal explanatory model of antipsychotic drug action. Recent discoveries extend our understanding of the neurochemistry of schizophrenia, with increasing evidence of dysfunction in glutamate and GABA as well as dopamine systems. In this review, we study the evidence for dopaminergic dysfunction in schizophrenia, drawing data from neurochemical imaging studies. We also review the NMDA receptor hypofunction hypothesis of schizophrenia as a supplementary explanatory model for the illness. We examine predictions made by the NMDA receptor hypofunction hypothesis and consider how they fit with current neurochemical findings in patients and animal models. We consider the case for glutamatergic excitotoxicity as a key process in the development and progression of schizophrenia, and suggest ways in which glutamate and dopamine dysregulation may interact in the condition.
精神分裂症的多巴胺假说，是抗精神病药物作用的主要解释模型。最近的发现扩展了我们对精神分裂症神经化学的理解，越来越多的证据表明谷氨酸、γ-氨基丁酸以及多巴胺系统均存在功能障碍。在本综述中，我们通过神经化学成像研究的数据，探讨精神分裂症中多巴胺能功能障碍的证据。我们还将精神分裂症的N-甲基-D-天冬氨酸（NMDA）受体功能减退假说作为该疾病的补充解释模型进行综述。我们检验NMDA受体功能减退假说所做出的预测，并思考这些预测与目前患者及动物模型的神经化学研究结果的契合程度。我们认为谷氨酸能兴奋性毒性是精神分裂症发生和发展的关键过程，并提出在这种情况下谷氨酸和多巴胺失调可能相互作用的方式。
