NO EVIDENCE OF LINKAGE BETWEEN THE DOPAMINE D-2 RECEPTOR GENE AND SCHIZOPHRENIA

The antipsychotic effects of dopamine D-2 receptor antagonists (neuroleptics) and the psychotomimetic effects of dopamine agonists suggest that a defect of the D-2 receptor gene might be a factor in the etiology of schizophrenia. Fifteen families that contained several members suffering from schizophrenia were tested for linkage between the D-2 receptor gene and schizophrenia. In addition, four flanking markers were tested. The mode of inheritance was assumed to be dominant. Five different models of the affection status, which ranged from a narrow to a broad definition of the affection status, were studied. Linkage analysis was carried out with dominant, recessive, and intermediate modes of transmission. Two-point and multipoint analyses between schizophrenia and the D-2 receptor gene resulted in log-likelihood differences < -2 for all five models, and linkage between this candidate gene and schizophrenia was excluded. A mutation in the D-2 receptor gene itself is therefore extremely unlikely to be related to a higher susceptibility to schizophrenia, at least in the present group of families.