1] Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY, USA [2] New York State Psychiatric Institute, New York, NY, USA.
1] Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY, USA [2] New York State Psychiatric Institute, New York, NY, USA [3] Department of Radiology, Columbia University College of Physicians and Surgeons, New York, NY, USA.
Mol Psychiatry. 2014 Jan;19(1):20-9. doi: 10.1038/mp.2013.136. Epub 2013 Oct 29.
Currently, all treatments for schizophrenia (SCZ) function primarily by blocking D(2)-type dopamine receptors. Given the limitations of these medications, substantial efforts have been made to identify alternative neurochemical targets for treatment development in SCZ. One such target is brain glutamate. The objective of this article is to review and synthesize the proton magnetic resonance spectroscopy ((1)H MRS) and positron emission tomography (PET)/single-photon emission computed tomography (SPECT) investigations that have examined glutamatergic indices in SCZ, including those of modulatory compounds such as glutathione (GSH) and glycine, as well as data from ketamine challenge studies. The reviewed (1)H MRS and PET/SPECT studies support the theory of hypofunction of the N-methyl-D-aspartate receptor (NMDAR) in SCZ, as well as the convergence between the dopamine and glutamate models of SCZ. We also review several advances in MRS and PET technologies that have opened the door for new opportunities to investigate the glutamate system in SCZ and discuss some ways in which these imaging tools can be used to facilitate a greater understanding of the glutamate system in SCZ and the successful and efficient development of new glutamate-based treatments for SCZ.
目前，所有治疗精神分裂症（SCZ）的方法主要都是通过阻断 D2 型多巴胺受体来实现的。鉴于这些药物的局限性，人们已经做出了巨大的努力来寻找治疗 SCZ 的替代神经化学靶点。其中一个靶点是大脑谷氨酸。本文的目的是回顾和综合质子磁共振波谱（(1)H MRS）和正电子发射断层扫描（PET）/单光子发射计算机断层扫描（SPECT）的研究，这些研究检查了 SCZ 中的谷氨酸能指数，包括调节化合物如谷胱甘肽（GSH）和甘氨酸的谷氨酸能指数，以及氯胺酮挑战研究的数据。综述的 (1)H MRS 和 PET/SPECT 研究支持了 SCZ 中 N-甲基-D-天冬氨酸受体（NMDAR）功能低下的理论，以及 SCZ 中多巴胺和谷氨酸模型的趋同。我们还回顾了 MRS 和 PET 技术的一些进展，这些进展为研究 SCZ 中的谷氨酸系统开辟了新的机会，并讨论了这些成像工具如何用于促进对 SCZ 中谷氨酸系统的更好理解以及成功和有效地开发新的基于谷氨酸的 SCZ 治疗方法。
