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Early treatment response in first episode psychosis: a 7-T magnetic resonance spectroscopic study of glutathione and glutamate

Early response to antipsychotic medications is one of the most important determinants of later symptomatic and functional outcomes in psychosis. Glutathione and glutamate have emerged as promising therapeutic targets for patients demonstrating inadequate response to dopamine-blocking antipsychotics....

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Autores principales: Dempster, Kara, Jeon, Peter, MacKinley, Michael, Williamson, Peter, Théberge, Jean, Palaniyappan, Lena
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7387300/
https://www.ncbi.nlm.nih.gov/pubmed/32205866
http://dx.doi.org/10.1038/s41380-020-0704-x
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author Dempster, Kara
Jeon, Peter
MacKinley, Michael
Williamson, Peter
Théberge, Jean
Palaniyappan, Lena
author_facet Dempster, Kara
Jeon, Peter
MacKinley, Michael
Williamson, Peter
Théberge, Jean
Palaniyappan, Lena
author_sort Dempster, Kara
collection PubMed
description Early response to antipsychotic medications is one of the most important determinants of later symptomatic and functional outcomes in psychosis. Glutathione and glutamate have emerged as promising therapeutic targets for patients demonstrating inadequate response to dopamine-blocking antipsychotics. Nevertheless, the role of these neurochemicals in the mechanism of early antipsychotic response remains poorly understood. Using a longitudinal design and ultrahigh field 7-T magnetic resonance spectroscopy (MRS) protocol in 53 subjects, we report the association between dorsal anterior cingulate cortex glutamate and glutathione, with time to treatment response in drug naive (34.6% of the sample) or minimally medicated first episode patients with schizophreniform disorder, schizophrenia, and schizoaffective disorder. Time to response was defined as the number of weeks required to reach a 50% reduction in the PANSS-8 scores. Higher glutathione was associated with shorter time to response (F = 4.86, P = 0.017), while higher glutamate was associated with more severe functional impairment (F = 5.33, P = 0.008). There were no significant differences between patients and controls on measures of glutamate or glutathione. For the first time, we have demonstrated an association between higher glutathione and favorable prognosis in FEP. We propose that interventions that increase brain glutathione levels may improve outcomes of early intervention in psychosis.
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spelling pubmed-73873002020-08-11 Early treatment response in first episode psychosis: a 7-T magnetic resonance spectroscopic study of glutathione and glutamate Dempster, Kara Jeon, Peter MacKinley, Michael Williamson, Peter Théberge, Jean Palaniyappan, Lena Mol Psychiatry Immediate Communication Early response to antipsychotic medications is one of the most important determinants of later symptomatic and functional outcomes in psychosis. Glutathione and glutamate have emerged as promising therapeutic targets for patients demonstrating inadequate response to dopamine-blocking antipsychotics. Nevertheless, the role of these neurochemicals in the mechanism of early antipsychotic response remains poorly understood. Using a longitudinal design and ultrahigh field 7-T magnetic resonance spectroscopy (MRS) protocol in 53 subjects, we report the association between dorsal anterior cingulate cortex glutamate and glutathione, with time to treatment response in drug naive (34.6% of the sample) or minimally medicated first episode patients with schizophreniform disorder, schizophrenia, and schizoaffective disorder. Time to response was defined as the number of weeks required to reach a 50% reduction in the PANSS-8 scores. Higher glutathione was associated with shorter time to response (F = 4.86, P = 0.017), while higher glutamate was associated with more severe functional impairment (F = 5.33, P = 0.008). There were no significant differences between patients and controls on measures of glutamate or glutathione. For the first time, we have demonstrated an association between higher glutathione and favorable prognosis in FEP. We propose that interventions that increase brain glutathione levels may improve outcomes of early intervention in psychosis. Nature Publishing Group UK 2020-03-24 2020 /pmc/articles/PMC7387300/ /pubmed/32205866 http://dx.doi.org/10.1038/s41380-020-0704-x Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Immediate Communication
Dempster, Kara
Jeon, Peter
MacKinley, Michael
Williamson, Peter
Théberge, Jean
Palaniyappan, Lena
Early treatment response in first episode psychosis: a 7-T magnetic resonance spectroscopic study of glutathione and glutamate
title Early treatment response in first episode psychosis: a 7-T magnetic resonance spectroscopic study of glutathione and glutamate
title_full Early treatment response in first episode psychosis: a 7-T magnetic resonance spectroscopic study of glutathione and glutamate
title_fullStr Early treatment response in first episode psychosis: a 7-T magnetic resonance spectroscopic study of glutathione and glutamate
title_full_unstemmed Early treatment response in first episode psychosis: a 7-T magnetic resonance spectroscopic study of glutathione and glutamate
title_short Early treatment response in first episode psychosis: a 7-T magnetic resonance spectroscopic study of glutathione and glutamate
title_sort early treatment response in first episode psychosis: a 7-t magnetic resonance spectroscopic study of glutathione and glutamate
topic Immediate Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7387300/
https://www.ncbi.nlm.nih.gov/pubmed/32205866
http://dx.doi.org/10.1038/s41380-020-0704-x
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