Department of Psychiatry, Juntendo University Schizophrenia Projects, Juntendo University, School of Medicine, Tokyo, Japan.
Prog Neuropsychopharmacol Biol Psychiatry. 2011 Jan 15;35(1):29-39. doi: 10.1016/j.pnpbp.2010.08.027. Epub 2010 Sep 7.
Hypo-function of N-methyl d-aspartate (NMDA) receptors is strongly involved in the brain pathophysiology of schizophrenia. Several excitatory amino acids, such as endogenous glutamate, glycine, serine and alanine, which are involved in glutamate neurotransmission via NMDA receptors, were studied to further understand the pathophysiology of schizophrenia and to find a biological marker for this disease, particularly in peripheral blood. In this literature review, we connect several earlier clinical studies and several studies of excitatory amino acid levels in peripheral blood in a historical context. Finally, we join these results and our previous studies, the Juntendo University Schizophrenia Projects (JUSP), which investigated plasma glutamatergic amino acid levels in detail, and considered whether these amino acid levels may be diagnostic, therapeutic, or symptomatic biological markers. This review concludes that peripheral blood levels of endogenous glycine and alanine could be a symptomatic marker in schizophrenia, while peripheral blood levels of exogenous glycine and alanine in augmentation therapies could be therapeutic markers. Noteworthy peripheral blood levels of endogenous d-serine could reflect its brain levels, and may prove to be a useful diagnostic and therapeutic marker in schizophrenia. In addition, measurements of new endogenous molecules, such as glutathione, are promising. Finally, for future therapies with glutamatergic agents still being examined in animal studies, the results of these biological marker studies may lay the foundation for the development of next-generation antipsychotics.
N-甲基-D-天冬氨酸（NMDA）受体功能低下与精神分裂症的大脑病理生理学密切相关。几种兴奋性氨基酸，如内源性谷氨酸、甘氨酸、丝氨酸和丙氨酸，通过 NMDA 受体参与谷氨酸能神经传递，这些氨基酸被研究用于进一步了解精神分裂症的病理生理学，并寻找这种疾病的生物标志物，特别是在外周血中。在这篇文献综述中，我们将几个早期的临床研究和外周血中兴奋性氨基酸水平的研究置于历史背景下进行了关联。最后，我们结合这些结果和我们之前的研究，即顺天堂大学精神分裂症项目（JUSP），详细研究了血浆谷氨酸能氨基酸水平，并考虑了这些氨基酸水平是否可能成为诊断、治疗或症状生物标志物。这篇综述的结论是，外周血内源性甘氨酸和丙氨酸水平可能是精神分裂症的症状标志物，而增效治疗中外周血内源性甘氨酸和丙氨酸水平可能是治疗标志物。值得注意的是，外周血内源性 D-丝氨酸水平可能反映其大脑水平，有望成为精神分裂症的有用诊断和治疗标志物。此外，新的内源性分子如谷胱甘肽的测量也很有前途。最后，对于仍在动物研究中进行的谷氨酸能药物的未来治疗，这些生物标志物研究的结果可能为开发下一代抗精神病药物奠定基础。
