Cytochrome P450 II D6 gene polymorphisms and the neuroleptic-induced extrapyramidal symptoms in Japanese schizophrenic patients.

OBJECTIVE

The purpose of this study was to examine whether the neuroleptic-induced extrapyramidal symptoms are associated with the CYP2D6 activity.

METHODS

The CYP2D6 gene polymorphisms (CYP2D62, CYP2D63, CYP2D64, CYP2D610, and CYP2D6*12) were genotyped in 196 normal controls and 320 schizophrenic patients receiving neuroleptics. The relationships with susceptibility to extrapyramidal symptoms (EPS) and tardive dyskinesia, and with steady-state serum haloperidol levels in maintenance therapy, were investigated.

RESULTS

The allele frequency of CYP2D62 was significantly higher, while that of CYP2D610 tended to be higher in the schizophrenic patients susceptible to acute EPS. The steady-state serum haloperidol levels per daily dosage were observed to be significantly higher in schizophrenic patients with the mutant-type homozygote of CYP2D62, while this difference was trend level in those of CYP2D610. However, no significant difference was observed in the distribution of both CYP2D62 (C2938T) and CYP2D610 (C188T) polymorphisms between schizophrenic patients with or without tardive dyskinesia.

CONCLUSION

The present results suggest that the homozygotes of CYP2D62 and CYP2D610 appear to be a susceptibility factor for developing acute EPS in schizophrenic patients and for impaired neuroleptic metabolism in Japanese schizophrenic patients.