D2 dopamine receptor gene polymorphism discriminates two kinds of novelty seeking

Cloningerʹs psychobiological model of personality as applied to substance misuse has received mixed support. Contrary to the model, recent data suggest that a combination of high novelty seeking (NS) and high harm avoidance (HA) represents a significant risk for the development of severe substance misuse. A genetic polymorphism previously implicated in severe substance dependence, the Al allele of the D2 dopamine receptor (DRD2) gene, was examined in relation to NS and HA amongst 203 adolescent boys. Specifically, we hypothesized that subjects with the Al+ allele (Al/Al and A1/A2 genotypes) would report stronger NS and would exhibit a more positive relationship between NS and HA than those with the A1− allele (A2/A2 genotypes). These predictions were supported. The correlation between NS and HA in 81 A1+ allelic boys (r=0.27, P=0.02), and that in the 122 Al− allelic boys (r=−0.15, P=0.09), indicated that this relationship differed according to allelic status (F=8.52, P<0.004). Among those with the A1− allele, the present results are consistent with the traditional view that novelty seeking provides positive reinforcement, or the fulfillment of appetitive drives. In contrast, novelty seeking in those with the A1+ allele appears to include a negative reinforcement or self-medicating function.