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

Abstract

The purpose of this study was to examine whether the neuroleptic-induced extrapyramidal symptoms are associated with the CYP2D6 activity. The CYP2D6 gene polymorphisms (CYP2D6*2, CYP2D6*3, CYP2D6*4, CYP2D6*10, 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. The allele frequency of CYP2D6*2 was significantly higher, while that of CYP2D6*10 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 CYP2D6*2, while this difference was trend level in those of CYP2D6*10. However, no significant difference was observed in the distribution of both CYP2D6*2 (C2938T) and CYP2D6*10 (C188T) polymorphisms between schizophrenic patients with or without tardive dyskinesia. The present results suggest that the homozygotes of CYP2D6*2 and CYP2D6*10 appear to be a susceptibility factor for developing acute EPS in schizophrenic patients and for impaired neuroleptic metabolism in Japanese schizophrenic patients.