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

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posted on 2023-06-10, 00:41 authored by Grant McQueen, Kyra-Verena Sendt, Amy Gillespie, Alessia Avila, John Lally, Kalliopi Vallianatou, Nynn Chang, Diogo Ferreira, Faith Borgan, Oliver D Howes, Gareth J Barker, David J Lythgoe, James StoneJames Stone, Philip McGuire, James H MacCabe, Alice Egerton
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.

History

Publication status

  • Published

File Version

  • Published version

Journal

Schizophrenia Bulletin

ISSN

0586-7614

Publisher

Oxford University Press

Issue

3

Volume

47

Page range

662-671

Event location

United States

Department affiliated with

  • BSMS Neuroscience Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2021-08-20

First Open Access (FOA) Date

2021-08-20

First Compliant Deposit (FCD) Date

2021-08-20

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