Journal
SCHIZOPHRENIA BULLETIN
Volume 47, Issue 3, Pages 662-671Publisher
OXFORD UNIV PRESS
DOI: 10.1093/schbul/sbaa156
Keywords
H-1-MRS; magnetic resonance spectroscopy; antipsychotic; anterior cingulate cortex; caudate; psychosis
Categories
Funding
- Medical Research Council, UK [MR/L003988/1]
- National Institute for Health Research (NIHR), Biomedical Research Centre at South London and Maudsley National Health Service (NHS) Foundation Trust and King's College London
- MRC [MR/L003988/1] Funding Source: UKRI
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The study found that 12 weeks of clozapine treatment was associated with a longitudinal reduction in glutamate concentration in the caudate nucleus, but not in the ACC. The reduction in caudate glutamate concentration was positively correlated with percentage improvement in symptoms.
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 (H-1-MRS) measured concentrations, corrected for voxel tissue content, of glutamate (Glu(corr)), and glutamate plus glutamine (Glx(corr)) 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 naive), 25 completed H-1-MRS at both timepoints. 12 weeks of clozapine was associated with a longitudinal reduction in Glu(corr). in the caudate (n = 23, F = 7.61 P = .01) but not in the ACC (is = 24, F = 0.02, P = .59). Percentage reduction in caudate Glu(corr) 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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