title: Age modulates the effect of COMT genotype on delay discounting behavior.
abstract: 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.
authors.affiliation: Neurobiology Curriculum, University of North Carolina, Davie Hall, Chapel Hill, NC 27599-3270, USA.
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Smith
authors.forename: Charlotte A
authors.initials: CA
authors.lastname: Boettiger
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000483:Alleles; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D003430:Cross-Sectional Studies; D005260:Female; D005838:Genotype; D006801:Humans; D007175:Impulsive Behavior / Q000235:genetics* / Q000523:psychology*; D008297:Male; D020641:Polymorphism, Single Nucleotide
chemical_list: D002394:Catechol O-Methyltransferase