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Pharmacogenetics of Antipsychotic-Induced Movement Disorders as a Resource for Better Understanding Parkinson’s Disease Modifier Genes

Antipsychotic-induced movement disorders are major side effects of antipsychotic drugs among schizophrenia patients, and include antipsychotic-induced parkinsonism (AIP) and tardive dyskinesia (TD). Substantial pharmacogenetic work has been done in this field, and several susceptibility variants hav...

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Autores principales: Greenbaum, Lior, Lerer, Bernard
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4335175/
https://www.ncbi.nlm.nih.gov/pubmed/25750634
http://dx.doi.org/10.3389/fneur.2015.00027
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author Greenbaum, Lior
Lerer, Bernard
author_facet Greenbaum, Lior
Lerer, Bernard
author_sort Greenbaum, Lior
collection PubMed
description Antipsychotic-induced movement disorders are major side effects of antipsychotic drugs among schizophrenia patients, and include antipsychotic-induced parkinsonism (AIP) and tardive dyskinesia (TD). Substantial pharmacogenetic work has been done in this field, and several susceptibility variants have been suggested. In this paper, the genetics of antipsychotic-induced movement disorders is considered in a broader context. We hypothesize that genetic variants that are risk factors for AIP and TD may provide insights into the pathophysiology of motor symptoms in Parkinson’s disease (PD). Since loss of dopaminergic stimulation (albeit pharmacological in AIP and degenerative in PD) is shared by the two clinical entities, genes associated with susceptibility to AIP may be modifier genes that influence clinical expression of PD motor sub-phenotypes, such as age at onset, disease severity, or rate of progression. This is due to their possible functional influence on compensatory mechanisms for striatal dopamine loss. Better compensatory potential might be beneficial at the early and later stages of the PD course. AIP vulnerability variants could also be related to latent impairment in the nigrostriatal pathway, affecting its functionality, and leading to subclinical dopaminergic deficits in the striatum. Susceptibility of PD patients to early development of l-DOPA induced dyskinesia (LID) is an additional relevant sub-phenotype. LID might share a common genetic background with TD, with which it shares clinical features. Genetic risk variants may predispose to both phenotypes, exerting a pleiotropic effect. According to this hypothesis, elucidating the genetics of antipsychotic-induced movement disorders may advance our understanding of multiple aspects of PD and it clinical course, rendering this a potentially rewarding field of study.
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spelling pubmed-43351752015-03-06 Pharmacogenetics of Antipsychotic-Induced Movement Disorders as a Resource for Better Understanding Parkinson’s Disease Modifier Genes Greenbaum, Lior Lerer, Bernard Front Neurol Neuroscience Antipsychotic-induced movement disorders are major side effects of antipsychotic drugs among schizophrenia patients, and include antipsychotic-induced parkinsonism (AIP) and tardive dyskinesia (TD). Substantial pharmacogenetic work has been done in this field, and several susceptibility variants have been suggested. In this paper, the genetics of antipsychotic-induced movement disorders is considered in a broader context. We hypothesize that genetic variants that are risk factors for AIP and TD may provide insights into the pathophysiology of motor symptoms in Parkinson’s disease (PD). Since loss of dopaminergic stimulation (albeit pharmacological in AIP and degenerative in PD) is shared by the two clinical entities, genes associated with susceptibility to AIP may be modifier genes that influence clinical expression of PD motor sub-phenotypes, such as age at onset, disease severity, or rate of progression. This is due to their possible functional influence on compensatory mechanisms for striatal dopamine loss. Better compensatory potential might be beneficial at the early and later stages of the PD course. AIP vulnerability variants could also be related to latent impairment in the nigrostriatal pathway, affecting its functionality, and leading to subclinical dopaminergic deficits in the striatum. Susceptibility of PD patients to early development of l-DOPA induced dyskinesia (LID) is an additional relevant sub-phenotype. LID might share a common genetic background with TD, with which it shares clinical features. Genetic risk variants may predispose to both phenotypes, exerting a pleiotropic effect. According to this hypothesis, elucidating the genetics of antipsychotic-induced movement disorders may advance our understanding of multiple aspects of PD and it clinical course, rendering this a potentially rewarding field of study. Frontiers Media S.A. 2015-02-20 /pmc/articles/PMC4335175/ /pubmed/25750634 http://dx.doi.org/10.3389/fneur.2015.00027 Text en Copyright © 2015 Greenbaum and Lerer. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Greenbaum, Lior
Lerer, Bernard
Pharmacogenetics of Antipsychotic-Induced Movement Disorders as a Resource for Better Understanding Parkinson’s Disease Modifier Genes
title Pharmacogenetics of Antipsychotic-Induced Movement Disorders as a Resource for Better Understanding Parkinson’s Disease Modifier Genes
title_full Pharmacogenetics of Antipsychotic-Induced Movement Disorders as a Resource for Better Understanding Parkinson’s Disease Modifier Genes
title_fullStr Pharmacogenetics of Antipsychotic-Induced Movement Disorders as a Resource for Better Understanding Parkinson’s Disease Modifier Genes
title_full_unstemmed Pharmacogenetics of Antipsychotic-Induced Movement Disorders as a Resource for Better Understanding Parkinson’s Disease Modifier Genes
title_short Pharmacogenetics of Antipsychotic-Induced Movement Disorders as a Resource for Better Understanding Parkinson’s Disease Modifier Genes
title_sort pharmacogenetics of antipsychotic-induced movement disorders as a resource for better understanding parkinson’s disease modifier genes
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4335175/
https://www.ncbi.nlm.nih.gov/pubmed/25750634
http://dx.doi.org/10.3389/fneur.2015.00027
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