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.

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    11/2014; 1. DOI:10.3389/fnut.2014.00019
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    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
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    ABSTRACT: Rates of alcohol and other drug use rise sharply throughout adolescence and peak in the early 20s. Likewise, prevalence of first-time substance use disorder (SUD) and past-year SUD both peak between ages 18–23. SUD is associated with a host of negative outcomes and is a serious health concern. Understanding the mechanisms that precede the onset and escalation of substance use is crucial in order to develop more effective prevention and intervention strategies for children and adolescents at risk for SUD. In this review, we discuss recent findings from functional neuroimaging studies in children, adolescents, and emerging adults that focus on uncovering the neural underpinnings of SUD risk. The focus is on inhibitory control and reward circuitry due to their involvement in risk-taking behaviors, which are heightened in adolescence and may facilitate substance use. We discuss con-vergences in the literature and highlight findings suggesting that the association between SUD risk and neurofunctioning may be moderated by age, gender, and history of substance use. Recommendations for future directions are also discussed.
    06/2015; 2(2). DOI:10.1007/s40429-015-0048-9


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May 30, 2014