Changes in brain glutamate on switching to clozapine in treatment-resistant schizophrenia

McQueen, Grant, Sendt, Kyra-Verena, Gillespie, Amy, Avila, Alessia, Lally, John, Vallianatou, Kalliopi, Chang, Nynn, Ferreira, Diogo, Borgan, Faith, Howes, Oliver D, Barker, Gareth J, Lythgoe, David J, Stone, James M, McGuire, Philip, MacCabe, James H and Egerton, Alice (2021) Changes in brain glutamate on switching to clozapine in treatment-resistant schizophrenia. Schizophrenia Bulletin, 47 (3). pp. 662-671. ISSN 0586-7614

[img] PDF - Published Version
Available under License Creative Commons Attribution.

Download (1MB)


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.

Item Type: Article
Keywords: 1H-MRS, anterior cingulate cortex, antipsychotic, caudate, magnetic resonance spectroscopy, psychosis
Schools and Departments: Brighton and Sussex Medical School > Neuroscience
SWORD Depositor: Mx Elements Account
Depositing User: Mx Elements Account
Date Deposited: 20 Aug 2021 14:29
Last Modified: 20 Aug 2021 14:30

View download statistics for this item

📧 Request an update