Gene-gene interaction associated with neural reward sensitivity.
Proc Natl Acad Sci U S A
; 104(19): 8125-30, 2007 May 08.
Article
em En
| MEDLINE
| ID: mdl-17483451
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Recompensa
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Catecol O-Metiltransferase
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Córtex Pré-Frontal
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Corpo Estriado
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Proteínas da Membrana Plasmática de Transporte de Dopamina
Tipo de estudo:
Diagnostic_studies
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Risk_factors_studies
Limite:
Adolescent
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Adult
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2007
Tipo de documento:
Article