Dopamine Receptor D4 Polymorphisms Research Articles

The relationship between dopamine D2 receptor polymorphism at the Taq1 A locus and therapeutic response to nemonapride, a selective dopamine antagonist, in schizophrenic patients.

Previous studies have demonstrated that subjects with one or two A1 alleles of dopamine D2 receptor (DRD2) polymorphism at the Taq1 A locus have lower DRD2 density than those with no A1 allele. The present study aimed to examine whether the Taq1 A DRD2 genotypes are related to therapeutic response to nemonapride, a selective dopamine antagonist, in schizophrenic patients. The subjects were 25 acutely exacerbated schizophrenic inpatients who had received no medication for at least 1 month before the study. The fixed dose (18 mg/day) of nemonapride was administered to each patient for 3 weeks. The clinical status was prospectively monitored by the Brief Psychiatric Rating Scale (BPRS) before, and 3 weeks after, the treatment. The Taq1 A genotypes (A1 and A2 alleles) were determined by the polymerase chain reaction method. Three patients were homozygous for the A1 allele, 11 were heterozygous for the A1 and A2 alleles, and 11 were homozygous for the A2 allele. The patients with one or two A1 alleles (n = 14) showed significantly higher percentage improvement in total BPRS and positive symptoms than those with no A1 allele (n = 11) after 3-week treatment while the percentage improvement in other subgrouped symptoms (negative, anxiety-depression, excitement and cognitive symptoms) was similar between the two genotype groups. The present results suggest that the Taq1 A DRD2 polymorphism is related to early therapeutic response to nemonapride in schizophrenic patients, possibly by modifying the efficiency of DRD2 antagonism of the drug in the central nervous system.

Allelic variants of dopamine receptor D4 (DRD4) and serotonin receptor 5HT2c (HTR2c) and temperament factors: Replication tests

The contribution of genetic factors to personality differences between individuals is evidenced by twin and adoption studies. Ebstein et al. [1996, 1997a, 1997b] reported an association between the long repeat allele of the dopamine D4-exon-III receptor polymorphism and the human personality dimension novelty seeking (NS), between the 5HT2c-ser-23 allele and reward dependence, and an interaction between both receptor polymorphisms and reward dependence. Subsequent replication tests mainly reported controversial results for the association between DRD4-exon-III long repeat and NS. We examined a homogeneous study population of 190 healthy male students of middle European descent, aged between 20 and 30 years using Cloninger's TPQ in order to replicate Ebstein's findings. Using a significance level of 1%, no association between the long repeat of the DRD4-exon-III polymorphism and NS and between the 5HT2c receptor polymorphism and reward dependence was found, but a significant interaction effect of DRD4 and 5HT2c receptor polymorphisms on reward dependence was observed in accordance to Ebstein's report. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:168–172, 1999. © 1999 Wiley-Liss, Inc.

Allelic variants of dopamine receptor D4 (DRD4) and serotonin receptor 5HT2c (HTR2c) and temperament factors: Replication tests

The contribution of genetic factors to personality differences between individuals is evidenced by twin and adoption studies. Ebstein et al. [1996, 1997a, 1997b] reported an association between the long repeat allele of the dopamine D4-exon-III receptor polymorphism and the human personality dimension novelty seeking (NS), between the 5HT2c-ser-23 allele and reward dependence, and an interaction between both receptor polymorphisms and reward dependence. Subsequent replication tests mainly reported controversial results for the association between DRD4-exon-III long repeat and NS. We examined a homogeneous study population of 190 healthy male students of middle European descent, aged between 20 and 30 years using Cloninger's TPQ in order to replicate Ebstein's findings. Using a significance level of 1%, no association between the long repeat of the DRD4-exon-III polymorphism and NS and between the 5HT2c receptor polymorphism and reward dependence was found, but a significant interaction effect of DRD4 and 5HT2c receptor polymorphisms on reward dependence was observed in accordance to Ebstein's report.