Age modulates the effect of COMT genotype on delay discounting behavior

Abstract

Rationale and objective A form of impulsivity, the tendency to choose immediate over delayed rewards (delay-discounting) has been associated with a single nucleotide polymorphism (SNP) in the catechol-O-methyltransferase (COMT) gene (COMTval158met; rs4680). However, the existing data regarding the nature of this association are in conflict. We have previously reported that adults homozygous for valine (val) at the COMTval158met SNP demonstrate greater delaydiscounting than do methionine (met) allele carriers (Boettiger et al., J Neurosci 27:14383-14391, 2007). In contrast, a recent study of adolescent males found that those with the met/met genotype demonstrate greater delay-discounting than do val-Allele carriers (Paloyelis et al., Neuropsychopharmacology 35:2414-2426, 2010). Based on reported age-related changes in frontal dopamine function and COMT expression, we hypothesized that the association of COMT genotype with delay-discounting behavior is modulated by age from late adolescence to young adulthood. Methods To test this hypothesis, we genotyped late adolescents (18-21 years; n072) and adults (22-40 years; n070) for the COMTval158met polymorphism, measured their delay-discounting behavior, and tested for an interaction between age group and COMT genotype. Results This cross-sectional study found that age modulates COMTval 158met genotype effects on delay-discounting behavior. Among met-carriers, delay-discounting was negatively correlated with age from late adolescence to adulthood, while among val/val individuals delay-discounting was positively correlated with age across this range. Conclusions These results confirm our previous finding of enhanced delay-discounting among val/val adults relative to met-Allele carriers, and help reconcile existing literature. We propose a single U-shaped model of the relationship between frontal DA levels and impulsive choice that accounts for both adolescent and adult data. © Springer-Verlag 2012.