2010年4月
Association of the HSPG2 Gene with Neuroleptic-Induced Tardive Dyskinesia
NEUROPSYCHOPHARMACOLOGY
- 巻
- 35
- 号
- 5
- 開始ページ
- 1155
- 終了ページ
- 1164
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1038/npp.2009.220
- 出版者・発行元
- NATURE PUBLISHING GROUP
Tardive 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. Neuropsychopharmacology (2010) 35, 1155-1164; doi: 10.1038/npp.2009.220; published online 13 January 2010
- リンク情報
- ID情報
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- DOI : 10.1038/npp.2009.220
- ISSN : 0893-133X
- eISSN : 1740-634X
- Web of Science ID : WOS:000275648000011