GABRB1 Single Nucleotide Polymorphism Associated with Altered Brain Responses
(but not Performance) during Measures of Impulsivity and Reward Sensitivity in
Human Adolescents
Variations in genes encoding several GABAA 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 GABAA 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 GABAA receptors may play a role
in excitability of brain regions important in controlling reward-related
behavior, which may contribute to susceptibility to addictive behavior