| Autor: |
Duka T; School of Psychology, University of Sussex Falmer, UK., Nikolaou K; School of Psychology, University of Sussex Falmer, UK., King SL; School of Psychology, University of Sussex Falmer, UK., Banaschewski T; Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University Mannheim, Germany., Bokde AL; Institute of Neuroscience, Trinity College Dublin Dublin, Ireland., Büchel C; Department of Systems Neuroscience, Universitätsklinikum Hamburg Eppendorf Hamburg, Germany., Carvalho FM; Institute of Psychiatry, Kings College London London, UK., Conrod PJ; Institute of Psychiatry, Kings College LondonLondon, UK; Department of Psychiatry, Université de Montréal, CHU Ste Justine HospitalMontréal, QC, Canada., Flor H; Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University Mannheim, Germany., Gallinat J; Department of Systems Neuroscience, Universitätsklinikum Hamburg Eppendorf Hamburg, Germany., Garavan H; Institute of Neuroscience, Trinity College DublinDublin, Ireland; Departments of Psychiatry and Psychology, University of VermontBurlington, VT, USA., Heinz A; Clinic for Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Germany., Jia T; Institute of Psychiatry, Kings College London London, UK., Gowland P; School of Psychology, University of Nottingham Nottingham, UK., Martinot JL; INSERM, UMR 1000, Research Unit Imaging and Psychiatry, IFR49, CEA, DSV, I2BM-Service Hospitalier Frédéric Joliot Orsay, France., Paus T; School of Psychology, University of NottinghamNottingham, UK; Rotman Research Institute, University of TorontoToronto, ON, Canada., Rietschel M; Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University Mannheim, Germany., Robbins TW; Department of Psychology, University of Cambridge Cambridge, UK., Smolka M; Department of Psychiatry and Psychotherapy, Technische Universität Dresden Dresden, Germany., Schumann G; Institute of Psychiatry, Kings College LondonLondon, UK; MRC Social, Genetic and Developmental Psychiatry (SGDP) CentreLondon, UK., Stephens DN; School of Psychology, University of Sussex Falmer, UK. |
| Abstrakt: |
Variations in genes encoding several GABA A receptors have been associated with human drug and alcohol abuse. Among these, a number of human studies have suggested an association between GABRB1 , the gene encoding GABA A receptor β1 subunits, with Alcohol dependence (AD), both on its own and comorbid with other substance dependence and psychiatric illnesses. In the present study, we hypothesized that the GABRB1 genetically-associated increased risk for developing alcoholism may be associated with impaired behavioral control and altered sensitivity to reward, as a consequence of altered brain function. Exploiting the IMAGEN database (Schumann et al., 2010), we explored in a human adolescent population whether possession of the minor (T) variant of the single nucleotide polymorphism (SNP) rs2044081 is associated with performance of tasks measuring aspects of impulsivity, and reward sensitivity that are implicated in drug and alcohol abuse. Allelic variation did not associate with altered performance in either a stop-signal task (SST), measuring one aspect of impulsivity, or a monetary incentive delay (MID) task assessing reward anticipation. However, increased functional magnetic resonance imaging (fMRI) blood-oxygen-level dependent (BOLD) response in the right hemisphere inferior frontal gyrus (IFG), left hemisphere caudate/insula and left hemisphere inferior temporal gyrus (ITG) during MID performance was higher in the minor (T) allelic group. In contrast, during SST performance, the BOLD response found in the right hemisphere supramarginal gyrus, right hemisphere lingual and left hemisphere inferior parietal gyrus indicated reduced responses in the minor genotype. We suggest that β1-containing GABA A receptors may play a role in excitability of brain regions important in controlling reward-related behavior, which may contribute to susceptibility to addictive behavior. |
