Association study of Cannabinoid receptor 1 (CNR1) gene in tardive dyskinesia

A. K. Tiwari, C. C. Zai, O. Likhodi, A. N. Voineskos, H. Y. Meltzer, J. A. Lieberman, S. G. Potkin, G. Remington, D. J. Müller, J. L. Kennedy*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

Tardive dyskinesia (TD) is a severe, debilitating movement disorder observed in 25-30% of the patients treated with typical antipsychotics. Cannabinoid receptor 1 (CNR1) activators tend to inhibit movement, an effect prevented by rimonabant and other selective CNR1 antagonists. Furthermore, CNR1 receptor is downregulated in Huntington's disease and upregulated in Parkinson's disease. Twenty tagSNPs spanning the CNR1 gene were analyzed in schizophrenia patients of European ancestry (n=191; 74 with TD). Significant genotypic (P=0.012) and allelic (P=0.012) association was observed with rs806374 (T>C). Carriers of the CC genotype were more likely to be TD positive (CC vs TT+TC, odds ratio=3.4 (1.5-7.8), P=0.003) and had more severe TD (CC vs TT+TC; 9.52±9.2 vs 5.62±6.9, P=0.046). These results indicate a possible role of CNR1 in the development of TD in our patient population. However, these observations are marginal after correcting for multiple testing and need to be replicated in a larger patient population.

Original languageEnglish (US)
Pages (from-to)260-266
Number of pages7
JournalPharmacogenomics Journal
Volume12
Issue number3
DOIs
StatePublished - Jun 2012

Funding

Canadian Institutes of Health Research (CIHR) operating grants to JLK and DJM; a NARSAD Young Investigator Award to DJM, MH41468, the Prentiss Foundation, Ritter Foundation, Hintz family and the Peterson Family to HYM; The Bebensee Foundation fellowship to CCZ and CIHR postdoctoral fellowship to AKT. AKT/CCZ/DJM: report no competing interests. HYM has received grants or is a consultant to Abbott Labs, ACADIA, Bristol Myers Squibb, Eli Lilly, Janssen, Pfizer, Astra Zeneca, Glaxo Smith Kline, Memory, Cephalon, Minster, Aryx and BiolineRx. HYM is a shareholder of ACADIA. JAL reports that he serves on the Advisory Board of Bioline, GlaxoSmithKline, Intracellular Therapies, Eli Lilly, Pierre Fabre, Psychogenics and Wyeth. He does not receive financial compensation or salary support for his participation as an advisor. He receives grant support from Allon, Forest Labs, Merck and Pfizer; he holds a patent from Repligen. JLK has been a consultant to GSK, Sanofi-Aventis and Dainippon-Sumitomo.

Keywords

  • CNR1
  • association
  • genetics
  • movement
  • schizophrenia
  • tardive dyskinesia

ASJC Scopus subject areas

  • Genetics
  • Molecular Medicine
  • Pharmacology

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