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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...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2015
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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. |
format | Online Article Text |
id | pubmed-4335175 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
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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