title: Gene-gene interaction associated with neural reward sensitivity.
abstract: Reward processing depends on dopaminergic neurotransmission and is modulated by factors affecting dopamine (DA) reuptake and degradation. We used fMRI and a guessing task sensitive to reward-related activation in the prefrontal cortex and ventral striatum to study how individual variation in genes contributing to DA reuptake [DA transporter (DAT)] and degradation [catechol-o-methyltransferase (COMT)] influences reward processing. Prefrontal activity, evoked by anticipation of reward irrespective of reward probability and magnitude, was COMT genotype-dependent. Volunteers homozygous for the Met allele, associated with lower enzyme activity and presumably greater DA availability, showed larger responses compared with volunteers homozygous for the Val allele. A similar COMT effect was observed in the ventral striatum. As reported previously, the ventral striatum was also found to code gain-related expected value, i.e., the product of reward magnitude and gain probability. Individual differences in ventral striatal sensitivity for value were in part explained by an epistatic gene-gene interaction between COMT and DAT. Although most genotype combinations exhibited the expected activity increase with more likely and larger rewards, two genotype combinations (COMT Met/Met DAT 10R and COMT Val/Val 9R) were associated with blunted ventral striatal responses. In view of a consistent relationship between reduced reward sensitivity and addiction, our findings point to a potential genetic basis for vulnerability to addiction.
authors.affiliation: NeuroImage Nord, Department of Systems Neuroscience, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany.
authors.forename: Juliana
authors.initials: J
authors.lastname: Yacubian
authors.forename: Tobias
authors.initials: T
authors.lastname: Sommer
authors.forename: Katrin
authors.initials: K
authors.lastname: Schroeder
authors.forename: Jan
authors.initials: J
authors.lastname: Gläscher
authors.forename: Raffael
authors.initials: R
authors.lastname: Kalisch
authors.forename: Boris
authors.initials: B
authors.lastname: Leuenberger
authors.forename: Dieter F
authors.initials: DF
authors.lastname: Braus
authors.forename: Christian
authors.initials: C
authors.lastname: Büchel
mesh_terms: D000293:Adolescent; D000328:Adult; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D003342:Corpus Striatum / Q000502:physiology*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D017397:Prefrontal Cortex / Q000502:physiology*; D012201:Reward
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D002394:Catechol O-Methyltransferase