Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, UK.
Curr Pharm Biotechnol. 2012 Jun;13(8):1500-12. doi: 10.2174/138920112800784961.
Over the last 50 years, evidence for central involvement of glutamatergic neurotransmission in the pathophysiology of schizophrenia has accumulated. Recent advances in neuroimaging technology now allow several components of glutamatergic neurotransmission to be assessed in the living human brain. Positron emission tomography (PET) or single photon emission tomography (SPET) in combination with select radiotracers allows visualization of glutamatergic receptors in vivo, and magnetic resonance (MR) - based techniques allow mapping of the effects of glutamatergic agents on regional brain activation, and the measurement of regional glutamate concentrations. These imaging studies have provided evidence for regional glutamatergic abnormalities in psychosis, and are beginning to describe both the evolution of these abnormalities over the course of the illness and their response to therapeutic intervention. In parallel, advances in small animal imaging and the development of animal models have provided a platform to explore the neuropathological consequences of glutamatergic abnormality, and the potential antipsychotic efficacy of novel compounds. The molecular diversity of the glutamatergic system has driven the design of several compounds targeting aspects of glutamatergic transmission, and clinical trials have yielded encouraging results. Here, we review the contribution of imaging studies to date in understanding glutamatergic abnormalities in psychosis, and discuss the potential of new glutamatergic compounds for treatment of the disorder.
在过去的 50 年中，越来越多的证据表明谷氨酸能神经传递在精神分裂症的病理生理学中起核心作用。神经影像学技术的最新进展使得人们能够在活体人类大脑中评估几种谷氨酸能神经传递成分。正电子发射断层扫描（PET）或单光子发射断层扫描（SPET）与选择性放射性示踪剂结合使用，可以在体内可视化谷氨酸能受体，而基于磁共振（MR）的技术可以绘制谷氨酸能药物对区域大脑激活的影响图，并测量区域谷氨酸浓度。这些影像学研究为精神疾病中的区域性谷氨酸能异常提供了证据，并开始描述这些异常在疾病过程中的演变及其对治疗干预的反应。与此同时，小动物成像技术的进步和动物模型的发展为探索谷氨酸能异常的神经病理学后果以及新型化合物的潜在抗精神病疗效提供了平台。谷氨酸能系统的分子多样性促使设计了几种针对谷氨酸能传递各个方面的化合物，临床试验取得了令人鼓舞的结果。在这里，我们回顾了迄今为止影像学研究在理解精神分裂症中谷氨酸能异常方面的贡献，并讨论了新型谷氨酸能化合物治疗该疾病的潜力。
