Age modulates the effect of COMT genotype on delay discounting behavior.

Smith CT, Boettiger CA
Psychopharmacology (Berl). 2012 222 (4): 609-17

PMID: 22349272 · PMCID: PMC3401276 · DOI:10.1007/s00213-012-2653-9

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 delay-discounting 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; n = 72) and adults (22-40 years; n = 70) 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 COMTval¹⁵⁸met 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.

MeSH Terms (12)

Adolescent Adult Age Factors Alleles Catechol O-Methyltransferase Cross-Sectional Studies Female Genotype Humans Impulsive Behavior Male Polymorphism, Single Nucleotide

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