Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, De Crespigny Park, London, UK.
Department of Psychiatry, Royal College of Surgeons in Ireland, Dublin, Ireland.
Schizophr Bull. 2021 Apr 29;47(3):662-671. doi: 10.1093/schbul/sbaa156.
It has been suggested that the antipsychotic clozapine may modulate brain glutamate, and that this effect could contribute to its efficacy in treatment-resistant schizophrenia (TRS). The aim of this study was to examine the effects of clozapine on brain glutamate in TRS longitudinally. This study examined individuals with TRS before and 12 weeks after switching from a non-clozapine antipsychotic to treatment with clozapine as part of their normal clinical care. Proton magnetic resonance spectroscopy (1H-MRS) measured concentrations, corrected for voxel tissue content, of glutamate (Glucorr), and glutamate plus glutamine (Glxcorr) in the anterior cingulate cortex (ACC) and right caudate nucleus. Symptoms were monitored using the Positive and Negative Syndrome Scale (PANSS). Of 37 recruited patients (27 men, 39.30 years old, 84% clozapine naïve), 25 completed 1H-MRS at both timepoints. 12 weeks of clozapine was associated with a longitudinal reduction in Glucorr in the caudate (n = 23, F = 7.61 P = .01) but not in the ACC (n = 24, F = 0.02, P = .59). Percentage reduction in caudate Glucorr was positively correlated with percentage improvement in symptoms (total PANSS score, n = 23, r = .42, P = .04). These findings indicate that reductions in glutamate in the caudate nucleus may contribute to symptomatic improvement during the first months of clozapine treatment.
有人提出，抗精神病药氯氮平可能调节大脑谷氨酸，而这种作用可能有助于其在治疗抵抗性精神分裂症（TRS）中的疗效。本研究旨在纵向研究氯氮平对 TRS 患者大脑谷氨酸的影响。该研究在常规临床治疗中将非氯氮平抗精神病药转换为氯氮平治疗之前和 12 周后，对 TRS 患者进行了检查。质子磁共振波谱（1H-MRS）测量了额前扣带回皮质（ACC）和右侧尾状核谷氨酸（Glucorr）和谷氨酸加谷氨酰胺（Glxcorr）的浓度，经体素组织含量校正。使用阳性和阴性综合征量表（PANSS）监测症状。在招募的 37 名患者中（27 名男性，39.30 岁，84%为氯氮平初治），有 25 名患者在两个时间点完成了 1H-MRS。12 周的氯氮平治疗与尾状核中 Glucorr 的纵向降低相关（n = 23，F = 7.61，P =.01），但在 ACC 中没有相关性（n = 24，F = 0.02，P =.59）。尾状核 Glucorr 的百分比降低与症状的百分比改善呈正相关（总 PANSS 评分，n = 23，r =.42，P =.04）。这些发现表明，尾状核中谷氨酸的减少可能有助于氯氮平治疗的头几个月症状的改善。
