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

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: ORAA = 2.22, 95% CI: 1.23-4.03; 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 (n = 6 plus our own data) of COMT and TD, and found an association between ValVal genotype and TD in females (ORValVal = 1.63, 95% CI: 1.09-2.45; 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.