Dopamine D4 receptor gene polymorphisms and neuroleptic response in schizophrenia

• Published in: Biological psychiatry (1969) 1998-09, Vol.44 (6), p.483-487
• Main Authors: Hwu, Hai-Gwo, Hong, Chen-Jee, Lee, Yi-Ling, Lee, Ping-Chuan, Lee, Sandy F.C
• Format: Article
• Language: English
• Subjects: Adult; Antipsychotic Agents - therapeutic use; Biological and medical sciences; DNA - genetics; Dopamine; dopamine D4 receptor; Female; Genotype; Humans; Male; Medical sciences; negative symptoms; neuroleptic response; Neuropharmacology; Pharmacology. Drug treatments; Polymorphism, Genetic; Psycholeptics: tranquillizer, neuroleptic; Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; receptor gene; Receptors, Dopamine D2 - genetics; Receptors, Dopamine D4; Repetitive Sequences, Nucleic Acid; schizophrenia; Schizophrenia - drug therapy; Schizophrenia - genetics; Schizophrenic Psychology
• ISSN: 0006-3223; 1873-2402
• DOI: 10.1016/S0006-3223(98)00134-6

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 (χ 2 = 6.12, 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 was 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.