title: GABRB1Single Nucleotide Polymorphism Associated with Altered Brain Responses (but not Performance) during Measures of Impulsivity and Reward Sensitivity in Human Adolescents.
abstract: Variations in genes encoding several GABAAreceptors have been associated with human drug and alcohol abuse. Among these, a number of human studies have suggested an association betweenGABRB1, the gene encoding GABAAreceptor 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 theGABRB1genetically-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 GABAAreceptors may play a role in excitability of brain regions important in controlling reward-related behavior, which may contribute to susceptibility to addictive behavior.
authors.affiliation: School of Psychology, University of Sussex Falmer, UK.
authors.forename: Theodora
authors.initials: T
authors.lastname: Duka
authors.affiliation: School of Psychology, University of Sussex Falmer, UK.
authors.forename: Kyriaki
authors.initials: K
authors.lastname: Nikolaou
authors.affiliation: School of Psychology, University of Sussex Falmer, UK.
authors.forename: Sarah L
authors.initials: SL
authors.lastname: King
authors.affiliation: Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University Mannheim, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Banaschewski
authors.affiliation: Institute of Neuroscience, Trinity College Dublin Dublin, Ireland.
authors.forename: Arun L W
authors.initials: AL
authors.lastname: Bokde
authors.affiliation: Department of Systems Neuroscience, Universitätsklinikum Hamburg Eppendorf Hamburg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Büchel
authors.affiliation: Institute of Psychiatry, Kings College London London, UK.
authors.forename: Fabiana M
authors.initials: FM
authors.lastname: Carvalho
authors.affiliation: Institute of Psychiatry, Kings College LondonLondon, UK; Department of Psychiatry, Université de Montréal, CHU Ste Justine HospitalMontréal, QC, Canada.
authors.forename: Patricia J
authors.initials: PJ
authors.lastname: Conrod
authors.affiliation: Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University Mannheim, Germany.
authors.forename: Herta
authors.initials: H
authors.lastname: Flor
authors.affiliation: Department of Systems Neuroscience, Universitätsklinikum Hamburg Eppendorf Hamburg, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Gallinat
authors.affiliation: Institute of Neuroscience, Trinity College DublinDublin, Ireland; Departments of Psychiatry and Psychology, University of VermontBurlington, VT, USA.
authors.forename: Hugh
authors.initials: H
authors.lastname: Garavan
authors.affiliation: Clinic for Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Heinz
authors.affiliation: Institute of Psychiatry, Kings College London London, UK.
authors.forename: Tianye
authors.initials: T
authors.lastname: Jia
authors.affiliation: School of Psychology, University of Nottingham Nottingham, UK.
authors.forename: Penny
authors.initials: P
authors.lastname: Gowland
authors.affiliation: INSERM, UMR 1000, Research Unit Imaging and Psychiatry, IFR49, CEA, DSV, I2BM-Service Hospitalier Frédéric Joliot Orsay, France.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Martinot
authors.affiliation: School of Psychology, University of NottinghamNottingham, UK; Rotman Research Institute, University of TorontoToronto, ON, Canada.
authors.forename: Tomáš
authors.initials: T
authors.lastname: Paus
authors.affiliation: Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University Mannheim, Germany.
authors.forename: Marcella
authors.initials: M
authors.lastname: Rietschel
authors.affiliation: Department of Psychology, University of Cambridge Cambridge, UK.
authors.forename: Trevor W
authors.initials: TW
authors.lastname: Robbins
authors.affiliation: Department of Psychiatry and Psychotherapy, Technische Universität Dresden Dresden, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Smolka
authors.affiliation: Institute of Psychiatry, Kings College LondonLondon, UK; MRC Social, Genetic and Developmental Psychiatry (SGDP) CentreLondon, UK.
authors.forename: Gunter
authors.initials: G
authors.lastname: Schumann
authors.affiliation: School of Psychology, University of Sussex Falmer, UK.
authors.forename: David N
authors.initials: DN
authors.lastname: Stephens
keywords: GABAA receptor; alcohol abuse; fMRI; inferior frontal gyrus; insula; monetary incentive delay; stop signal; supramarginal gyrus