Dopamine D4 Receptor Gene Polymorphisms and Neuroleptic Response in Schizophrenia

Background: Dopamine D4 receptor (DRD4) gene polymorphisms are associated with various pharmacologic activities. This study investigated whether polymorphisms of 48-bp tandem repeats in the exon 3 of the DRD4 gene are related to neuroleptic response. Methods: The neuroleptic response at the acute stage of schizophrenia was assessed in 80 (48 men, 32 women) schizophrenic patients. The negative symptoms at remission were also rated . DRD4 genotype was established using the polymerase chain reaction. Patients with genotypes containing an allele with only two repeats (2-2, 2 -3 2-4, 2 -6) were assigned to group I (n = 38). Those homozygous for four 48-bp repeats were assigned to group II (n = 42). Results: Thirteen (34.2 %) of the 38 group I subjects and 26( 61.9%) of the 42 group II subjects had good neuroleptic response during acute stage treatment (chi(2) = 612 df = 1, p < .02). In remission, the rates of negative symptoms of blunt affect, avolition, and global negative rating were higher in group I than in group II. This wets more prominent in men than in women. Conclusions: The presence of homozygous four 48-bp repeats in both alleles in exon 3 of the DRD4 gene is associated with good neuroleptic response during acute treatment, and with a lower prevalence of negative symptoms at remission, especially in male schizophrenic patients. (C) 1998 Society of Biological Psychiatry