Linked Life Data

20072119

Source:http://linkedlifedata.com/resource/pubmed/id/20072119

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pubmed-article:20072119pubmed:abstractTextTardive dyskinesia (TD) is characterized by repetitive, involuntary, and purposeless movements that develop in patients treated with long-term dopaminergic antagonists, usually antipsychotics. By a genome-wide association screening of TD in 50 Japanese schizophrenia patients with treatment-resistant TD and 50 Japanese schizophrenia patients without TD (non-TD group) and subsequent confirmation in independent samples of 36 treatment-resistant TD and 136 non-TD subjects, we identified association of a single nucleotide polymorphism, rs2445142, (allelic p=2 x 10(-5)) in the HSPG2 (heparan sulfate proteoglycan 2, perlecan) gene with TD. The risk allele was significantly associated with higher expression of HSPG2 in postmortem human prefrontal brain (p<0.01). Administration of daily injection of haloperidol (HDL) for 50 weeks significantly reduced Hspg2 expression in mouse brains (p<0.001). Vacuous chewing movements (VCMs) induced by 7-week injection of haloperidol-reserpine were significantly infrequent in adult Hspg2 hetero-knockout mice compared with wild-type littermates (p<0.001). Treatment by the acetylcholinesterase inhibitor, physostigmine, was significantly effective for reduction of VCMs in wild-type mice but not in Hspg2 hetero-knockout mice. These findings suggest that the HSPG2 gene is involved in neuroleptic-induced TD and higher expression of HSPG2, probably even after antipsychotic treatment, and may be associated with TD susceptibility.lld:pubmed
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pubmed-article:20072119pubmed:articleTitleAssociation of the HSPG2 gene with neuroleptic-induced tardive dyskinesia.lld:pubmed
pubmed-article:20072119pubmed:affiliationDepartment of Medical Genetics and Department of Molecular Neurobiology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan.lld:pubmed
pubmed-article:20072119pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:20072119pubmed:publicationTypeResearch Support, Non-U.S. Gov'tlld:pubmed
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