Glutamate, GABA and NAA in treatment-resistant schizophrenia: A systematic review of the effect of clozapine and group differences between clozapine-responders and non-responders.

Autor: Kristensen MWP; Mental Health Centre Glostrup, Copenhagen University Hospital - Mental Health Services CPH, Copenhagen, Denmark; Department of Clinical Medicine, University of Copenhagen, Blegdamsvej 3B, Copenhagen 2200, Denmark. Electronic address: rxg773@alumni.ku.dk., Biuk B; Mental Health Centre Glostrup, Copenhagen University Hospital - Mental Health Services CPH, Copenhagen, Denmark; Department of Clinical Medicine, University of Copenhagen, Blegdamsvej 3B, Copenhagen 2200, Denmark., Nielsen J; Mental Health Centre Glostrup, Copenhagen University Hospital - Mental Health Services CPH, Copenhagen, Denmark; Department of Clinical Medicine, University of Copenhagen, Blegdamsvej 3B, Copenhagen 2200, Denmark., Bojesen KB; Center for Neuropsychiatric Schizophrenia Research (CNSR), Mental Health Center Glostrup, Copenhagen University hospital - Mental Health Services CPH, Copenhagen, Denmark., Nielsen MØ; Mental Health Centre Glostrup, Copenhagen University Hospital - Mental Health Services CPH, Copenhagen, Denmark; Department of Clinical Medicine, University of Copenhagen, Blegdamsvej 3B, Copenhagen 2200, Denmark.
Jazyk: angličtina
Zdroj: Behavioural brain research [Behav Brain Res] 2025 Feb 28; Vol. 479, pp. 115338. Date of Electronic Publication: 2024 Nov 19.
DOI: 10.1016/j.bbr.2024.115338
Abstrakt: Treatment-resistance in patients with schizophrenia is a major obstacle for improving outcome in patients, especially in those not gaining from clozapine. Novel research implies that glutamatergic and GABAergic abnormalities may be present in treatment-resistant patients, and preclinical research suggests that clozapine affects the GABAergic system. Moreover, clozapine may have a neuroprotective role. To investigate these issues, we conducted a systematic review to evaluate the relationship between clozapine and in vivo measures of gamma-aminobutyric acid (GABA), glutamate (glu), and N-acetylaspartate (NAA) brain levels in treatment- and ultra-treatment-resistant schizophrenia patients (TRS and UTRS). Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we included three longitudinal and six cross sectional studies utilizing proton magnetic resonance spectroscopy (H-MRS) that explored brain metabolite levels in clozapine-treated patients. Findings were limited by a small number of studies and definite conclusions cannot be drawn, but the present studies may imply that clozapine reduces glutamate levels in striatal but not cortical areas, whereas glutamatergic metabolites and GABA levels may be increased in ACC in the combined group of TRS and UTRS. Clozapine may also increase NAA in cortical areas. Importantly, this review highlights the need for further clinical studies investigating the effect of clozapine on brain levels of glutamate, GABA, and NAA as well as metabolite group differences in patients with UTRS compared with TRS.
(Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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