Susceptibility to neuroleptic-induced tardive dyskinesia and the T102C polymorphism in the serotonin type 2A receptor

Background: Genetic factors have been implicated in the pathophysiology of the movement disorder tardive dyskinesia, which may involve dopamine-seroto nin interaction. Case-control association studies have identified the T102C polymorphism of the 5-HT2A receptor gene as being associated with schizoph renia and responsiveness to clozapine. In this study, we examine the associ ation of this polymorphism in the 5-HT2A receptor gene as a risk factor for developing schizophrenia and tardive dyskinesia from prolonged treatment w ith neuroleptics. Methods: Ninety-seven healthy control subjects with no history of mental il lness and 221 schizophrenic patients (87 with tardive dyskinesia, 134 witho ut) were genotyped by PCR-RFLP. Results: Comparison between cases and control subjects revealed no signific ant association between the C allele and schizophrenia. There was significa nt difference in allele frequency (p = .044, OR = 1.54 95% CI = 1.02-2.33) between patients who developed tardive dyskinesia and those who did not. Si gnificant difference remains even after adjusting for age and neuroleptic d osage (p = .041) with the odds ratio at 1.64 (95% CI 1.02-2.62). Conclusions: A genetic variant of the 5-HT2A receptor may be associated wit h neuroleptic-induced tardive dyskinesia in schizophrenia. Further studies are needed to replicate the finding. The role of 5-HT2A receptor in the eti ology of tardive dyskinesia or treatment-resistant schizophrenia should be further investigated. (C) 2001 Society of Biological Psychiatry.