GENETIC POLYMORPHISMS FOR DRUG-METABOLISM (CYP2D6) AND TARDIVE-DYSKINESIA IN SCHIZOPHRENIA

In the present study, the occurrence of tardive dyskinesia (TD) in chr onic schizophrenic patients was investigated in relation to pharmacoge netic polymorphisms. It is known that the metabolism of important neur oleptic drugs is influenced by polymorphisms of the CYP2D6 gene, which encodes the cytochrome P450 enzyme debrisoquine/spartein hydroxylase. Forty-five patients meeting the DSM IV criteria for schizophrenia, ch ronic course, were recruited. The patients were examined for the mutat ions CYP2D63, CYP2D6*4 and CYP2D6*5. The CYP2D6 genotype distribution in the patient group did not differ from that in healthy Caucasian po pulations. Tardive dyskinesia was found in 26 patients (57.8%). When c omparing patients without CYP2D6 mutations with patients heterozygous for one mutation, we found a higher incidence of TD in the latter (81. 3% vs. 46.4%, p=0.031, multiple regression analysis), which demonstrat es a significant influence of the CYP2D6 genotype of the manifestation of TD. As slight differences in the metabolism of drugs in patients h eterozygous for CYP2D6 mutations and patients without such mutations a re known, we conclude that heterozygous carriers of 2D6 mutated allele s may show an increased susceptibility to developing TD. (C) 1998 Else vier Science B,V. All rights reserved.