Tsai G, Yang P, Chung L C, Lange N, Coyle J T
Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston 02129, USA.
Biol Psychiatry. 1998 Dec 1;44(11):1081-9. doi: 10.1016/s0006-3223(98)00279-0.
Hypofunction of N-methyl-D-aspartate (NMDA) subtype glutamate receptor has been implicated in the pathophysiology of schizophrenia. D-serine is a full agonist of the glycine site of NMDA receptor, an endogenous cotransmitter enriched in corticolimbic regions and distributed in parallel with NMDA receptor. Supplementation of D-serine may improve the symptoms of schizophrenia.
Thirty-one Taiwanese schizophrenic patients enrolled in a 6-week double-blind, placebo-controlled trial of D-serine (30 mg/kg/day), which was added to their stable antipsychotic regimens. Of these, 28 completed the trial. Measures of clinical efficacy, side effects, and serum levels of amino acids and D-serine were determined every other week. Wisconsin Card Sorting Test (WCST) was performed at the beginning and end of the trial.
Patients who received D-serine treatment revealed significant improvements in their positive, negative, and cognitive symptoms as well as some performance in WCST. D-serine levels at week 4 and 6 significantly predicted the improvements. D-serine was well tolerated and no significant side effects were noted.
The significant improvement with the D-serine further supports the hypothesis of NMDA receptor hypofunction in schizophrenia. Given the effects of D-serine on positive symptoms, a trial of D-serine alone in schizophrenia should be considered.
N-甲基-D-天冬氨酸（NMDA）亚型谷氨酸受体功能减退与精神分裂症的病理生理学有关。D-丝氨酸是NMDA受体甘氨酸位点的完全激动剂，是一种内源性共递质，在皮质边缘区域富集，并与NMDA受体平行分布。补充D-丝氨酸可能改善精神分裂症的症状。
31名台湾精神分裂症患者参加了一项为期6周的双盲、安慰剂对照试验，在其稳定的抗精神病治疗方案中添加D-丝氨酸（30mg/kg/天）。其中，28名患者完成了试验。每隔一周测定临床疗效、副作用以及氨基酸和D-丝氨酸的血清水平。在试验开始和结束时进行威斯康星卡片分类测验（WCST）。
接受D-丝氨酸治疗的患者在阳性、阴性和认知症状以及WCST的一些表现方面有显著改善。第4周和第6周的D-丝氨酸水平显著预测了改善情况。D-丝氨酸耐受性良好，未观察到明显副作用。
D-丝氨酸的显著改善进一步支持了精神分裂症中NMDA受体功能减退的假说。鉴于D-丝氨酸对阳性症状的影响，应考虑在精神分裂症中单独进行D-丝氨酸试验。
