DOPAMINE-D4 RECEPTOR GENE POLYMORPHISMS AND NEUROLEPTIC RESPONSE IN SCHIZOPHRENIA

Background: Dopamine D4 receptor (DRD4) gene polymorphisms are associa ted with various pharmacologic activities. This study investigated whe ther polymorphisms of 48-bp tandem repeats in the exon 3 of the DRD4 g ene are related to neuroleptic response. Methods: The neuroleptic resp onse at the acute stage of schizophrenia was assessed in 80 (48 men, 3 2 women) schizophrenic patients. The negative symptoms at remission we re also rated. DRD4 genotype was established using the polymerase chai n 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 s tage 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 promine nt 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 low er prevalence of negative symptoms at remission, especially in male sc hizophrenic patients. (C) 1998 Society of Biological Psychiatry.