DOPAMINE D3-RECEPTOR GENE VARIANT AND SUSCEPTIBILITY TO TARDIVE-DYSKINESIA IN SCHIZOPHRENIC-PATIENTS

Schizophrenia is a serious psychiatric illness with a life-time risk o f approximately one percent, Many of the patients, but not all, benefi t from treatment with anti-psychotic drugs known to block dopamine D2- like receptors, The use of conventional neuroleptics is, however, hamp ered by the risk of extrapyramidal side-effects, Tardive dyskinesia (T D) is usually regarded as the most serious of these drug-induced movem ent disorders due to its high prevalence and potentially irreversible nature, In this study, we have investigated the genetic variation of t he dopamine D3 receptor gene (DRD3) as a putative risk factor for TD i n schizophrenic patients receiving long-term anti-psychotic drug thera py, We found a high frequency (22-24%) of homozygosity for the Ser9Gly variant (allele 2) of the DRD3 gene among subjects with Tn in both a cross-sectional and a longitudinal evaluation, as compared with the re lative underrepresentation (4-6%) of this genotype in patients with no or fluctuating TD, This result indicates that autosomal inheritance o f two polymorphic Ser9Gly alleles (2-2 genotype), but not homozygosity for the wild-type allele (1-1 genotype), is a susceptibility factor f or the development of TD an observation which may improve the understa nding of the pathophysiological mechanisms of TD and influence the des ign and choice of future anti-psychotic drugs, The correlation between a serious motor side-effect and a genetic marker could lead to select ion bias in the sampling of schizophrenic patients for genetic studies , and may therefore explain the apparent association reported between susceptibility for schizophrenia per se and homozygosity for the DRD3 gene.