Association of the HSPG2 Gene with Neuroleptic-Induced Tardive Dyskinesia View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2010-04

AUTHORS

Aoi Syu, Hiroki Ishiguro, Toshiya Inada, Yasue Horiuchi, Syunsuke Tanaka, Maya Ishikawa, Makoto Arai, Masanari Itokawa, Kazuhiro Niizato, Shuji Iritani, Norio Ozaki, Makoto Takahashi, Akiyoshi Kakita, Hitoshi Takahashi, Hiroyuki Nawa, Kazuko Keino-Masu, Eri Arikawa-Hirasawa, Tadao Arinami

ABSTRACT

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. More... »

PAGES

1155

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/npp.2009.220

DOI

http://dx.doi.org/10.1038/npp.2009.220

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1000992644

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/20072119


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