Changes in Brain Glutamate on Switching to Clozapine in Treatment-Resistant Schizophrenia.
Changes in Brain Glutamate on Switching to Clozapine in Treatment-Resistant Schizophrenia.
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DOI：
10.1093/schbul/sbaa156
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发表时间：
2021-04-29
影响因子：
6.6
通讯作者：
Egerton A
中科院分区：
文献类型：
--
作者：
McQueen G;Sendt KV;Gillespie A;Avila A;Lally J;Vallianatou K;Chang N;Ferreira D;Borgan F;Howes OD;Barker GJ;Lythgoe DJ;Stone JM;McGuire P;MacCabe JH;Egerton A
有研究表明抗精神病药物氯氮平可能调节脑谷氨酸，这种作用可能有助于其治疗难治性精神分裂症（TRS）。本研究的目的是纵向研究氯氮平对TRS脑谷氨酸的影响。本研究检查了TRS患者在从非氯氮平抗精神病药物转为氯氮平治疗之前和12周后的情况，这是他们正常临床护理的一部分。质子磁共振波谱（1H-MRS）测量了前扣带皮层（ACC）和右尾状核中谷氨酸（Glucorr）和谷氨酸加谷氨酰胺（Glxcorr）的浓度，校正了体素组织含量。使用阳性和阴性症状量表（PANSS）监测症状。在37名招募的患者中（27名男性，39.30岁，84%氯氮平naïve）， 25名患者在两个时间点完成1H-MRS。12周氯氮平与尾状核纵向血糖降低相关（n = 23, F = 7.61 P = 0.01），但与ACC无关（n = 24, F = 0.02, P = 0.59）。尾状核血糖降低百分比与症状改善百分比呈正相关（PANSS总评分，n = 23, r = 0.42, P = 0.04）。这些发现表明尾状核谷氨酸的减少可能有助于氯氮平治疗最初几个月的症状改善。
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.
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