FAILURE TO FIND EVIDENCE FOR LINKAGE OR ASSOCIATION BETWEEN THE DOPAMINE D-3 RECEPTOR GENE AND SCHIZOPHRENIA

Objective: This study was performed to assess the possible involvement of the dopamine D-3 receptor gene (DRD3) in the etiology of schizophr enia. The authors' approach included a population study and a family s tudy using both parametric (lod score) and nonparametric (affected ped igree member) methods of linkage analysis. Method: Two different DNA m arkers were studied at the DRD3 locus. The family study included 35 mu ltiplex families of schizophrenic subjects for the linkage analyses. T he population study involved 50 unrelated schizophrenic subjects and 5 0 normal comparison subjects from the same ethnic and geographic origi n. Results: Whichever clinical classification was used to define the p athological phenotype (schizophrenia or schizophrenia spectrum), the r esults of the lod score and affected pedigree member studies did not p rovide arty evidence of linkage of the DRD3 gene to the illness. The n egative results of the association study reinforce these results. Conc lusions: The hypothesis that the DRD3 gene has a predisposing role in schizophrenia was not supported by these population and family studies . However, the possibility that this gene has a role in the etiology o f the disease cannot be definitely excluded because of the intrinsic l imitations of the methods of analysis and the number of subjects studi ed.