The catechol-O-methyl-transferase gene in tardive dyskinesia

Clement C. Zai, Arun K. Tiwari, Daniel J. Müller, Vincenzo De Luca, Takahiro Shinkai, Sajid Shaikh, Xingqun Ni, David Sibony, Aristotle N. Voineskos, Herbert Y. Meltzer, Jeffrey A. Lieberman, Steven G. Potkin, Gary Remington, James L. Kennedy

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


Tardive dyskinesia (TD) is a severe and potentially irreversible motor side effect linked to long-term antipsychotic exposure. Changes in dopamine neurotransmission have been implicated in the etiology of TD, and catechol-O-methyl-transferase (COMT) is an enzyme that metabolizes dopamine. Objectives. We investigated five single-nucleotide polymorphisms in addition to the functional Val158Met variant spanning the COMT gene for association with TD. Methods. We analyzed the six COMT single-nucleotide polymorphisms in a sample of schizophrenia/schizoaffective disorder patients (n=226; 196 Caucasians and 30 African Americans). Results. We found a significant association between the marker rs165599 in the 3′ untranslated region of COMT and TD (AA versus G-carrier: ORAA2.22, 95% CI:1.234.03; P=0.007). The association appeared to be originating from males. We did not find a significant association of the other five tested polymorphisms with TD in our samples. We performed a sex-stratified meta-analysis across all of the published studies (n6 plus our own data) of COMT and TD, and found an association between ValVal genotype and TD in females (ORValVal1.63, 95% CI: 1.092.45; P=0.019) but not in males. Conclusions. Overall, our results suggest that the COMT gene may have a minor but consistent role in TD, although sex-stratified studies with additional markers in larger clinical samples should be performed.

Original languageEnglish (US)
Pages (from-to)803-812
Number of pages10
JournalWorld Journal of Biological Psychiatry
Issue number6
StatePublished - Sep 2010


  • COMT
  • Meta-analysis
  • Pharmacogenetics
  • Schizophrenia
  • Tardive dyskinesia

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry


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