DOPAMINE D-3 RECEPTOR GENE VARIANTS AND SUBSTANCE-ABUSE IN SCHIZOPHRENIA

In an association study of the Bal I polymorphism in the dopamine D-3 receptor (DRD3) gene in a French Caucasian population, global comparis on of patients with schizophrenia (n = 89, DSM-III-R criteria) and con trols (n = 52) led to non-significant differences. However, the homozy gosity was significantly more frequent in schizophrenic patients with lifetime substance abuse comorbidity (n = 36) as compared to patients with no history of substance abuse (P = 0.010) or to controls (P = 0.0 47) and in neuroleptic responder patients as compared to treatment-ref ractory patients (n = 19; P = 0.037). The combined characteristics tre atment response and lifetime substance abuse were strongly associated with homozygosity. We propose that homozygosity for the Bal I polymorp hism DRD3 gene is associated with predisposition to substance abuse an d/or the pharmacosensitive characteristic of schizophrenia rather than with schizophrenia itself, an hypothesis in agreement with the positi ve association of this polymorphism with opiate dependence (see compan ion article by Duaux et al) and the involvement of DRD3 in both pharma codependence mechanisms and antipsychotic effects of neuroleptics.