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Gene-gene interaction associated with neural reward sensitivity.

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.

Pubmed ID: 17483451

Authors

  • Yacubian J
  • Sommer T
  • Schroeder K
  • Gläscher J
  • Kalisch R
  • Leuenberger B
  • Braus DF
  • Büchel C

Journal

Proceedings of the National Academy of Sciences of the United States of America

Publication Data

May 8, 2007

Associated Grants

None

Mesh Terms

  • Adolescent
  • Adult
  • Catechol O-Methyltransferase
  • Corpus Striatum
  • Dopamine Plasma Membrane Transport Proteins
  • Genotype
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Prefrontal Cortex
  • Reward