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-serotonin interaction. Case-control association studies have identified the T102C polymorphism of the 5-HT2A receptor gene as being associated with schizophrenia and responsiveness to clozapine. In this study, we examine the association of this polymorphism in the 5-HT2A 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-HT2A receptor may be associated with neuroleptic-induced tardive dyskinesia in schizophrenia. Further studies are needed to replicate the finding. The role of 5-HT2A receptor in the etiology of tardive dyskinesia or treatment-resistant schizophrenia should be further investigated.
Tan
E C
EC
Defence Medical Research Institute, Defence Science and Technology Agency, Republic of Singapore.
Chong
S A
SA
Mahendran
R
R
Dong
F
F
Tan
C H
CH
D014150:Antipsychotic Agents / Q000009:adverse effects*; D004298:Dopamine / Q000378:metabolism; D020820:Dyskinesias / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011985:Receptors, Serotonin / Q000235:genetics*; D012307:Risk Factors; D012559:Schizophrenia / Q000188:drug therapy* / Q000235:genetics; D012701:Serotonin / Q000378:metabolism
D014150:Antipsychotic Agents; D011985:Receptors, Serotonin; D012701:Serotonin; D004298:Dopamine