Efficacy of high-dose glycine in the treatment of enduring negative symptoms of schizophrenia
Efficacy of high-dose glycine in the treatment of enduring negative symptoms of schizophrenia
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DOI：
10.1001/archpsyc.56.1.29
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发表时间：
1999-01-01
影响因子：
--
通讯作者：
Lichtenstein, M
中科院分区：
文献类型：
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作者：
Heresco-Levy, U;Javitt, DC;Lichtenstein, M
背景：N-甲基-D-天冬氨酸(NMDA)受体介导的谷氨酸能神经传递功能障碍可能在精神分裂症阴性症状的病理生理机制中起重要作用。甘氨酸是一种小的非必需氨基酸，通过作用于NMDA受体复合体上的士的宁不敏感的结合部位，起到NMDA受体的强制性共激动剂的作用。因此，甘氨酸诱导的NMDA受体介导的神经传递的增强可能为改善精神分裂症持续的阴性症状提供一种潜在的安全可行的方法。方法：22例难治性精神分裂症患者参加了一项双盲、安慰剂对照、为期6周的交叉治疗试验，在正在服用的抗精神病药物的基础上，每天增加0.8g/kg的甘氨酸。临床评估包括简明精神病评定量表(BPRS)、阳性和阴性症状量表(PANSS)、锥体外系症状Simpson-Angus量表和异常不自主运动量表，在整个研究过程中每两周进行一次。结果：甘氨酸治疗耐受性良好，可引起血清甘氨酸(P=.001)和丝氨酸(P=.001)水平升高。甘氨酸治疗使(1)PANSS测量的阴性症状显著减少(P<；.001)30%+/-16%；(2)BPRS总分显著(P<；.001)改善30%+/-18%。阴性症状的改善与锥体外系效应或抑郁症状的改变无关。低甘氨酸治疗前血清甘氨酸水平显著预测临床疗效(r=0.80)。结论：本研究结果支持精神分裂症低谷氨酸能假说，为精神分裂症阴性症状的药物治疗提供了新的途径。
Background: Disturbances of N-methyl-D-aspartate (NMDA) receptor-mediated glutamatergic neurotransmission may play an important role in the pathophysiology of negative symptoms of schizophrenia. Glycine, a small nonessential amino acid, functions as an obligatory coagonist at NMDA receptors through its action at a strychnine-insensitive binding site on the NMDA receptor complex. Glycine-induced augmentation of NMDA receptor-mediated neurotransmission may thus offer a potentially safe and feasible approach for ameliorating persistent negative symptoms of schizophrenia.Methods: Twenty-two treatment-resistant schizophrenic patients participated in a double-blind, placebo-controlled, 6-week, crossover treatment trial with 0.8 g/kg per day of glycine added to their ongoing antipsychotic medication. Clinical assessments, including the Brief Psychiatric Rating Scale (BPRS), the Positive and Negative Syndrome Scale (PANSS), the Simpson-Angus Scale for Extrapyramidal Symptoms, and the Abnormal Involuntary Movement Scale, were performed biweekly throughout the study. Clinical laboratory values and amino acid serum levels were monitored.Results: Glycine treatment was well tolerated and induced increased glycine (P = .001) and serine (P = .001) serum levels. Glycine administration resulted in (1) a significant (P < .001) 30% +/- 16% reduction in negative symptoms, as measured by the PANSS; and (2) a significant (P < .001) 30% +/- 18% improvement in the BPRS total scores. The improvement in negative symptoms was unrelated to alterations in extrapyramidal effects or symptoms of depression. Low pretreatment glycine serum levels significantly predicted (r = 0.80) clinical response.Conclusion: These findings support hypoglutamatergic hypotheses of schizophrenia and suggest a novel approach for the pharmacotherapy of negative symptoms associated with this illness.