ADDITIVE CONTRIBUTION OF DRD3gly AND HT2CRser ALLELES TO SUSCEPTIBILITY TO TARDIVE DYSKINESIA IN PATIENTS WITH CHRONIC SCHIZOPHRENIARonnen H. Segman*, Uriel Heresco Levy, Boris Finkel, David Greenberg, Arturo Lerner, Avi Yakir, Michael Shlaffman, Abe Dorevich, Aida Shelevoy, Bernard Lerer.Biological Psychiatry Laboratory, Hadassah-Hebrew University Medical Center, Jerusalem, Israel. Email: sronnen@md2.huji.ac.il or lerer@cc.huji.ac.il We previously reported an excess of the dopamine D3 receptor glycine allele (DRD3gly) and of DRD3ser-gly and DRD3gly-gly genotypes in 53 chronic schizophrenia patients with tardive dyskinesia (TD) who were on a stable antipsychotic dose and were matched to 63 schizophrenia patients without TD (Segman et al., Mol Psychiatry, 4:247-253, 1999). We genotyped the same group of patients for a functionally relevant cysteine to serine polymorphism in the 5-HT2C receptor gene (HT2CR). There was an excess of HT2CRser alleles in the patients with TD (27.1% vs. 14.6%, p=.04). By ANCOVA (controlling for age at first antipsychotic treatment), there was a significant effect of HT2CR genotype on AIMS orofacial dyskinesia (AIMS-OFD) scores (F=3.47, df 2, p=.03). In a further ANCOVA in which the independent variables were carriage of DRD3gly or HT2CR-ser alleles, there was a significant main effect of both alleles on AIMS-OFD scores (p=.006 and p=.02) but no interaction. In a stepwise multiple regression, 8.2% of the variance in AIMS-OFD scores was accounted for by age at first antipsychotic treatment (p=.0001), 3.7% by gender (p=.02), 4.6% by DRD3gly (p=.02) and 4.2% by HT2CRser (p=.001). These findings support an additive contribution of DRD3gly and HT2CRser alleles to the complex TD phenotype. (Supported in part by a grant from the Hadassit Applied Research Fund).
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