D4 DOPAMINE-RECEPTOR (DRD4) ALLELES AND NOVELTY SEEKING IN SUBSTANCE-DEPENDENT, PERSONALITY-DISORDER, AND CONTROL SUBJECTS

Two reports have been published suggesting an association between the personality trait of novelty seeking and the DRD47R allele at the D4 dopamine-receptor locus (with heterozygotes or homozygotes for DRD47R having higher novelty seeking). We studied novelty seeking and four c oding-sequence polymorphisms affecting protein structure in the D4 dop amine-receptor gene (DRD4) in a sample of 341 American subjects, of wh om 224 are of primarily European ancestry and 117 are of primarily Afr ican ancestry. These subjects had diagnoses of substance dependence or personality disorder (PD) or were screened to exclude major psychiatr ic diagnosis. We found that, although the substance-dependent subjects had significantly higher novelty seeking than the control and PD subj ects, they did not differ in DRD47R allele frequency. There was no as sociation between any DRD4 polymorphism and novelty seeking in any pop ulation or diagnostic group, except for a significant association betw een the DRD47R allele and lower novelty seeking among European Americ an females and African American substance abusers. The novelty seeking of subjects heterozygous for a null mutation did not differ from that of subjects with two functional alleles. We conclude that the most li kely explanation of these results is that the DRD4 VNTR does not influ ence directly the trait of novelty seeking, in these samples.