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Role of COMT V158M Polymorphism in the Development of Dystonia after Administration of Antipsychotic Drugs

Antipsychotics (APDs) represent the main pharmacological strategy in the treatment of schizophrenia; however, their administration often may result in severe adverse effects, such as extrapyramidal symptoms. Typically, dystonic movements are considered the result of impaired function and/or abnormal...

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Autores principales: Nicotera, Antonio Gennaro, Di Rosa, Gabriella, Turriziani, Laura, Costanzo, Maria Cristina, Stracuzzi, Emanuela, Vitello, Girolamo Aurelio, Galati Rando, Rosanna, Musumeci, Antonino, Vinci, Mirella, Musumeci, Sebastiano Antonino, Calì, Francesco
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8533773/
https://www.ncbi.nlm.nih.gov/pubmed/34679357
http://dx.doi.org/10.3390/brainsci11101293
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author Nicotera, Antonio Gennaro
Di Rosa, Gabriella
Turriziani, Laura
Costanzo, Maria Cristina
Stracuzzi, Emanuela
Vitello, Girolamo Aurelio
Galati Rando, Rosanna
Musumeci, Antonino
Vinci, Mirella
Musumeci, Sebastiano Antonino
Calì, Francesco
author_facet Nicotera, Antonio Gennaro
Di Rosa, Gabriella
Turriziani, Laura
Costanzo, Maria Cristina
Stracuzzi, Emanuela
Vitello, Girolamo Aurelio
Galati Rando, Rosanna
Musumeci, Antonino
Vinci, Mirella
Musumeci, Sebastiano Antonino
Calì, Francesco
author_sort Nicotera, Antonio Gennaro
collection PubMed
description Antipsychotics (APDs) represent the main pharmacological strategy in the treatment of schizophrenia; however, their administration often may result in severe adverse effects, such as extrapyramidal symptoms. Typically, dystonic movements are considered the result of impaired function and/or abnormalities of dopaminergic neurotransmission/signaling in the basal ganglia. The catechol O-methyltransferase (COMT) gene is located within the 22q11.2 region, and its product is an enzyme involved in transferring a methyl group from S-adenosylmethionine to catecholamines, including dopamine. Studies showed that COMT Val158Met polymorphism modifies enzymatic activity and, consequently, synaptic dopamine concentration in specific brain areas. We identified a patient with 22q11.2 deletion syndrome presenting with cervical and trunk dystonia after paliperidone administration, which persisted even after drug discontinuation. Given the patient’s genetic condition, we hypothesized that the dopaminergic dysfunction had been aggravated by COMT involvement, thus causing dystonia. In line with this hypothesis, we carried out a study on psychiatric patients in chronic treatment with APD to evaluate the distribution of the COMT Val158Met polymorphism and its role in the onset of adverse extrapyramidal symptoms. The study included four patients with dystonia after administration of APDs compared to 17 patients who never presented adverse drug reactions. Our data suggest that the Val/Val and Met/Met polymorphisms of the COMT gene are associated with a protective effect for the development of collateral extrapyramidal symptoms in patients treated with APDs, while the Val/Met genotype could be considered a risk factor for the development of dystonia after APDs administration.
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spelling pubmed-85337732021-10-23 Role of COMT V158M Polymorphism in the Development of Dystonia after Administration of Antipsychotic Drugs Nicotera, Antonio Gennaro Di Rosa, Gabriella Turriziani, Laura Costanzo, Maria Cristina Stracuzzi, Emanuela Vitello, Girolamo Aurelio Galati Rando, Rosanna Musumeci, Antonino Vinci, Mirella Musumeci, Sebastiano Antonino Calì, Francesco Brain Sci Article Antipsychotics (APDs) represent the main pharmacological strategy in the treatment of schizophrenia; however, their administration often may result in severe adverse effects, such as extrapyramidal symptoms. Typically, dystonic movements are considered the result of impaired function and/or abnormalities of dopaminergic neurotransmission/signaling in the basal ganglia. The catechol O-methyltransferase (COMT) gene is located within the 22q11.2 region, and its product is an enzyme involved in transferring a methyl group from S-adenosylmethionine to catecholamines, including dopamine. Studies showed that COMT Val158Met polymorphism modifies enzymatic activity and, consequently, synaptic dopamine concentration in specific brain areas. We identified a patient with 22q11.2 deletion syndrome presenting with cervical and trunk dystonia after paliperidone administration, which persisted even after drug discontinuation. Given the patient’s genetic condition, we hypothesized that the dopaminergic dysfunction had been aggravated by COMT involvement, thus causing dystonia. In line with this hypothesis, we carried out a study on psychiatric patients in chronic treatment with APD to evaluate the distribution of the COMT Val158Met polymorphism and its role in the onset of adverse extrapyramidal symptoms. The study included four patients with dystonia after administration of APDs compared to 17 patients who never presented adverse drug reactions. Our data suggest that the Val/Val and Met/Met polymorphisms of the COMT gene are associated with a protective effect for the development of collateral extrapyramidal symptoms in patients treated with APDs, while the Val/Met genotype could be considered a risk factor for the development of dystonia after APDs administration. MDPI 2021-09-29 /pmc/articles/PMC8533773/ /pubmed/34679357 http://dx.doi.org/10.3390/brainsci11101293 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Nicotera, Antonio Gennaro
Di Rosa, Gabriella
Turriziani, Laura
Costanzo, Maria Cristina
Stracuzzi, Emanuela
Vitello, Girolamo Aurelio
Galati Rando, Rosanna
Musumeci, Antonino
Vinci, Mirella
Musumeci, Sebastiano Antonino
Calì, Francesco
Role of COMT V158M Polymorphism in the Development of Dystonia after Administration of Antipsychotic Drugs
title Role of COMT V158M Polymorphism in the Development of Dystonia after Administration of Antipsychotic Drugs
title_full Role of COMT V158M Polymorphism in the Development of Dystonia after Administration of Antipsychotic Drugs
title_fullStr Role of COMT V158M Polymorphism in the Development of Dystonia after Administration of Antipsychotic Drugs
title_full_unstemmed Role of COMT V158M Polymorphism in the Development of Dystonia after Administration of Antipsychotic Drugs
title_short Role of COMT V158M Polymorphism in the Development of Dystonia after Administration of Antipsychotic Drugs
title_sort role of comt v158m polymorphism in the development of dystonia after administration of antipsychotic drugs
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8533773/
https://www.ncbi.nlm.nih.gov/pubmed/34679357
http://dx.doi.org/10.3390/brainsci11101293
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