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

Abstract

Background: Genetic factors have been implicated in the pathophysiology of the movement disorder tardive dyskinesia, which may involve dopamine-serotonin interaction. Case-control association studies have identified the T102C polymorphism of the 5-HT 2A receptor gene as being associated with schizophrenia and responsiveness to clozapine. In this study, we examine the association of this polymorphism in the 5-HT 2A receptor gene as a risk factor for developing schizophrenia and tardive dyskinesia from prolonged treatment with neuroleptics. Methods: Ninety-seven healthy control subjects with no history of mental illness and 221 schizophrenic patients (87 with tardive dyskinesia, 134 without) were genotyped by PCR-RFLP. Results: Comparison between cases and control subjects revealed no significant association between the C allele and schizophrenia. There was significant 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. Significant difference remains even after adjusting for age and neuroleptic dosage ( p = .041) with the odds ratio at 1.64 (95% CI = 1.02–2.62). Conclusions: A genetic variant of the 5-HT 2A receptor may be associated with neuroleptic-induced tardive dyskinesia in schizophrenia. Further studies are needed to replicate the finding. The role of 5-HT 2A receptor in the etiology of tardive dyskinesia or treatment-resistant schizophrenia should be further investigated.