Sumiyoshi Tomiki, Anil A Elif, Jin Dai, Jayathilake Karu, Lee Myung, Meltzer Herbert Y
Department of Psychiatry, Division of Psychopharmacology, Vanderbilt University School of Medicine, Nashville, TN, USA.
Int J Neuropsychopharmacol. 2004 Mar;7(1):1-8. doi: 10.1017/S1461145703003900. Epub 2004 Jan 13.
Previous studies have suggested decreased N-methyl-D-aspartate (NMDA)-type glutamate receptor function may contribute to increased negative symptoms in patients with schizophrenia. Consistent with this hypothesis, glycine, a co-agonist at NMDA receptors, has been reported to improve negative symptoms associated with the illness. This study was performed to determine if plasma levels of glycine or its ratio to serine, a precursor of glycine, are decreased in patients with schizophrenia compared to normal control subjects or patients with major depression. We also tested the hypothesis that these amino acids were correlated with negative symptoms in subjects with schizophrenia. Plasma levels of glycine, serine, and their ratio, were compared in 144 patients with schizophrenia, 44 patients with major depression, and 49 normal control subjects. All subjects were medication-free. Psychopathology was evaluated using the Brief Psychiatric Rating Scale (BPRS). Plasma glycine levels and glycine/serine ratios were decreased in patients with schizophrenia relative to control subjects and patients with major depression. By contrast, serine levels were increased in patients with schizophrenia compared to normal subjects but not compared to major depression. Patients with major depression also had increased plasma serine levels and decreased glycine/serine ratios compared to normal controls, but glycine levels were not different from those of normal controls. In subjects with schizophrenia, glycine levels predicted the Withdrawal-Retardation score (BPRS), whereas no such correlation was found in subjects with major depression. These results provide additional evidence that decreased availability of glycine may be related to the pathophysiology of negative symptoms. The decreases in plasma glycine levels support the evidence for an abnormality in the glutamatergic system in schizophrenia, and provide additional support for efforts to improve negative symptoms by augmentation of antipsychotic drugs with agonists at the glycine site of the NMDA receptor.
先前的研究表明，N-甲基-D-天冬氨酸（NMDA）型谷氨酸受体功能降低可能导致精神分裂症患者的阴性症状增加。与该假设一致的是，据报道，NMDA受体的协同激动剂甘氨酸可改善与该疾病相关的阴性症状。本研究旨在确定与正常对照受试者或重度抑郁症患者相比，精神分裂症患者血浆中甘氨酸水平或其与甘氨酸前体丝氨酸的比值是否降低。我们还检验了以下假设：这些氨基酸与精神分裂症患者的阴性症状相关。比较了144例精神分裂症患者、44例重度抑郁症患者和49名正常对照受试者的血浆甘氨酸、丝氨酸水平及其比值。所有受试者均未服药。使用简明精神病评定量表（BPRS）评估精神病理学。与对照受试者和重度抑郁症患者相比，精神分裂症患者的血浆甘氨酸水平和甘氨酸/丝氨酸比值降低。相比之下，与正常受试者相比，精神分裂症患者的丝氨酸水平升高，但与重度抑郁症患者相比则无差异。与正常对照相比，重度抑郁症患者的血浆丝氨酸水平也升高，甘氨酸/丝氨酸比值降低，但甘氨酸水平与正常对照无差异。在精神分裂症患者中，甘氨酸水平可预测退缩-迟缓评分（BPRS），而在重度抑郁症患者中未发现此类相关性。这些结果提供了额外的证据，表明甘氨酸可用性降低可能与阴性症状的病理生理学有关。血浆甘氨酸水平降低支持了精神分裂症谷氨酸能系统异常的证据，并为通过在NMDA受体的甘氨酸位点使用激动剂增强抗精神病药物来改善阴性症状的努力提供了额外支持。
