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T19. GLUTAMATE AND RESPONSE TO CLOZAPINE IN TREATMENT RESISTANT SCHIZOPHRENIA
BACKGROUND: The mechanisms that underlie and may mediate the therapeutic response to clozapine in treatment resistant schizophrenia (TRS) are unclear. Basic science studies have indicated that clozapine may modulate brain glutamate, but this has not yet been investigated in man. The aim of this stud...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7233938/ http://dx.doi.org/10.1093/schbul/sbaa029.579 |
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author | Egerton, Alice McQueen, Grant Sendt, Kyra-Verena Gillespie, Amy Lally, John Borgan, Faith Howes, Oliver Barker, Gareth J Stone, James McGuire, Philip MacCabe, James |
author_facet | Egerton, Alice McQueen, Grant Sendt, Kyra-Verena Gillespie, Amy Lally, John Borgan, Faith Howes, Oliver Barker, Gareth J Stone, James McGuire, Philip MacCabe, James |
author_sort | Egerton, Alice |
collection | PubMed |
description | BACKGROUND: The mechanisms that underlie and may mediate the therapeutic response to clozapine in treatment resistant schizophrenia (TRS) are unclear. Basic science studies have indicated that clozapine may modulate brain glutamate, but this has not yet been investigated in man. The aim of this study was to determine whether clozapine alters brain glutamate levels in patients with TRS, and the associations with clinical outcome. METHODS: The study included patients with TRS who were about to start clozapine as part of their normal clinical care. Glutamate levels were measured in the anterior cingulate cortex (ACC) and right caudate nucleus using proton magnetic resonance spectroscopy (1H-MRS) before clozapine initiation (n=37) and again after 12-weeks of clozapine treatment (n=27). Symptoms were principally assessed using the PANSS. 1H-MRS scans were also acquired in a comparator group of healthy volunteers (n = 16). RESULTS: Over the 12 weeks of clozapine treatment there was a significant reduction in glutamate in the caudate (n = 22, F = 7.61 P < 0.05) but not in the ACC. The percentage reduction in caudate glutamate was positively associated with the percentage reduction in total PANSS score (n = 23, r = 0.42, P = 0.04). ACC Glx (glutamate plus glutamine) prior to clozapine initiation was higher in patients with TRS than in healthy volunteers (P=0.03). DISCUSSION: Improvements in symptoms following clozapine initiation in TRS may be related to reductions in glutamate in the caudate nucleus. In contrast, ACC glutamate levels appear to remain high during the first three months of clozapine treatment. |
format | Online Article Text |
id | pubmed-7233938 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-72339382020-05-23 T19. GLUTAMATE AND RESPONSE TO CLOZAPINE IN TREATMENT RESISTANT SCHIZOPHRENIA Egerton, Alice McQueen, Grant Sendt, Kyra-Verena Gillespie, Amy Lally, John Borgan, Faith Howes, Oliver Barker, Gareth J Stone, James McGuire, Philip MacCabe, James Schizophr Bull Poster Session III BACKGROUND: The mechanisms that underlie and may mediate the therapeutic response to clozapine in treatment resistant schizophrenia (TRS) are unclear. Basic science studies have indicated that clozapine may modulate brain glutamate, but this has not yet been investigated in man. The aim of this study was to determine whether clozapine alters brain glutamate levels in patients with TRS, and the associations with clinical outcome. METHODS: The study included patients with TRS who were about to start clozapine as part of their normal clinical care. Glutamate levels were measured in the anterior cingulate cortex (ACC) and right caudate nucleus using proton magnetic resonance spectroscopy (1H-MRS) before clozapine initiation (n=37) and again after 12-weeks of clozapine treatment (n=27). Symptoms were principally assessed using the PANSS. 1H-MRS scans were also acquired in a comparator group of healthy volunteers (n = 16). RESULTS: Over the 12 weeks of clozapine treatment there was a significant reduction in glutamate in the caudate (n = 22, F = 7.61 P < 0.05) but not in the ACC. The percentage reduction in caudate glutamate was positively associated with the percentage reduction in total PANSS score (n = 23, r = 0.42, P = 0.04). ACC Glx (glutamate plus glutamine) prior to clozapine initiation was higher in patients with TRS than in healthy volunteers (P=0.03). DISCUSSION: Improvements in symptoms following clozapine initiation in TRS may be related to reductions in glutamate in the caudate nucleus. In contrast, ACC glutamate levels appear to remain high during the first three months of clozapine treatment. Oxford University Press 2020-05 2020-05-18 /pmc/articles/PMC7233938/ http://dx.doi.org/10.1093/schbul/sbaa029.579 Text en © The Author(s) 2020. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Poster Session III Egerton, Alice McQueen, Grant Sendt, Kyra-Verena Gillespie, Amy Lally, John Borgan, Faith Howes, Oliver Barker, Gareth J Stone, James McGuire, Philip MacCabe, James T19. GLUTAMATE AND RESPONSE TO CLOZAPINE IN TREATMENT RESISTANT SCHIZOPHRENIA |
title | T19. GLUTAMATE AND RESPONSE TO CLOZAPINE IN TREATMENT RESISTANT SCHIZOPHRENIA |
title_full | T19. GLUTAMATE AND RESPONSE TO CLOZAPINE IN TREATMENT RESISTANT SCHIZOPHRENIA |
title_fullStr | T19. GLUTAMATE AND RESPONSE TO CLOZAPINE IN TREATMENT RESISTANT SCHIZOPHRENIA |
title_full_unstemmed | T19. GLUTAMATE AND RESPONSE TO CLOZAPINE IN TREATMENT RESISTANT SCHIZOPHRENIA |
title_short | T19. GLUTAMATE AND RESPONSE TO CLOZAPINE IN TREATMENT RESISTANT SCHIZOPHRENIA |
title_sort | t19. glutamate and response to clozapine in treatment resistant schizophrenia |
topic | Poster Session III |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7233938/ http://dx.doi.org/10.1093/schbul/sbaa029.579 |
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