Gene-gene interaction associated with neural reward sensitivity.

NeuroImage Nord, Department of Systems Neuroscience, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany.
Proceedings of the National Academy of Sciences (Impact Factor: 9.81). 06/2007; 104(19):8125-30. DOI: 10.1073/pnas.0702029104
Source: PubMed

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.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Los genes candidatos del sistema dopaminérgico se han descrito como elementos clave en la conformación del temperamento del ser humano. La enzima catecol-O-metiltransferasa (COMT) desempeña un papel decisivo en la inactivación de la dopamina, y recientemente, en estudios efectuados en adultos sanos, al igual que en individuos dependientes de la metaanfetamina, en el cuestionario Temperament and Character Inventory el polimorfismo de un solo nucleótido Val158Met (rs4680) del gen COMT se ha asociado a la dimensión temperamental de búsqueda de novedades (BN).MétodoEl objetivo del presente estudio fue examinar la asociación entre las dimensiones temperamentales del cuestionario Temperament and Character Inventory y la variación Val158Met del gen COMT en una muestra húngara de 117 pacientes dependientes de la heroína y 124 individuos de control, no dependientes.ResultadosEl análisis de casos-controles no demostró diferencias significativas en las distribuciones de alelo o genotipo. Sin embargo, la estrategia dimensional reveló una asociación entre el polimorfismo Val158Met del gen COMT y la dimensión temperamental de búsqueda de novedades (p = 0,01): tanto en los individuos de control como en los dependientes de opiáceos con genotipos Met/Met se demostraron puntuaciones más altas para BN comparado con aquellos con el alelo Val. Las puntuaciones obtenidas para BN también fueron significativamente más altas entre dependientes de opiáceos; sin embargo, no se detectó ninguna interacción entre el estado del grupo y el genotipo del gen COMT.ConclusiónPara pacientes dependientes de la heroína e individuos de control, con independencia de la situación del grupo, se ha demostrado la asociación del polimorfismo del gen COMT y la dimensión temperamental de búsqueda de novedades.
    04/2012; 19(2):39-45. DOI:10.1016/j.psiq.2012.04.001
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Cognitive performance is modulated by the neurotransmitter dopamine (DA). Recently, it has been proposed that DA has a strong impact on top-down but not on bottom-up selective visual attention. We tested this assumption by analyzing the influence of two gene variants of the dopaminergic system. Both the catechol O-methyltransferase (COMT) protein and the dopamine transporter (DAT) protein are crucial for the degradation and inactivation of DA. These metabolizing proteins modulate the availability of DA, especially in the prefrontal cortex and basal ganglia. The functional COMT Val158Met polymorphism of the COMT gene represents two coding variants, valine and methionine. In Met allele carriers, the COMT activity is reduced three- to fourfold. A variable number of tandem repeats (VNTR) polymorphism exists in the DAT1 gene, which encodes DAT. The DAT density was reported to be about 50 % higher for the DAT1 10-repeat than the DAT1 9-repeat allele. We assessed attention via two experimental tasks that predominantly measure either top-down processing (the Stroop task) or bottom-up processing (the Posner-Cuing task). Carriers of the Met allele of the COMT Val158Met polymorphism displayed better performance in the Stroop task, but did not outperform the other participants in the Posner-Cuing task. The same result was noted for carriers of the DAT1 10-repeat allele. From these findings, we suggest that normal variations of the dopaminergic system impact more strongly on top-down than on bottom-up attention.
    Cognitive Affective & Behavioral Neuroscience 09/2014; 15(1). DOI:10.3758/s13415-014-0320-9 · 3.87 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Prefrontal dopamine (DA) transmission participates in the reinforcement of reward-driven behaviors like eating. Because catechol-O-methyltransferase (COMT) degrades DA and is expressed in the prefrontal cortex, variation in the COMT gene may modulate eating behavior. Previous studies have shown that the met allele of the COMT val158met single nucleotide polymorphism (SNP) is associated with Bulimia Nervosa (BN). The specific aim of this study was to test whether the met allele increased risk for, and severity of, eating disorder symptomatology in community volunteers. Caucasian adults (N=1003; 51.2% female) from the University of Pittsburgh Adult Health and Behavior Project (AHAB) were genotyped and completed the Eating Disorders Inventory (EDI). Logistic and Poisson regression analyses assessed genotype-dependent presence and severity of eating disorder symptomatology. The met allele was significantly associated with the presence of symptoms on the Bulimia subscale and the severity of Body Dissatisfaction scores. All EDI subscales significantly predicted BMI. To our knowledge, these are the first data indicating that the COMT met allele increases risk for some symptoms of disordered eating, while increasing severity of others, in a community sample. These novel findings may have important implications for understanding the etiology of heterogeneous disordered eating phenotypes.
    Psychiatry Research 08/2014; DOI:10.1016/j.psychres.2014.08.037 · 2.68 Impact Factor


Available from
May 30, 2014