Effects of the DRD4 genotype on neural networks associated with executive functions in children and adolescents

Genetic variants within the dopamine D4 receptor gene (DRD4) are among the strongest and most consistently replicated molecular genetic findings in attentional functioning as well as attention deficit hyperactivity disorder (ADHD). Functionally, the 7-repeat allele of the DRD4-48 base pair repeat gene leads to a sub-sensitive postsynaptic D4 receptor, which is expressed at a particularly high density in the frontal lobes. We used fMRI to investigate the influence of the 7-repeat allele on BOLD (Blood Oxygen Level Dependency) responses in 26 healthy children and adolescents while they performed a combined stimulus-response Incompatibility Task (IC) and a Time Discrimination Task (TT). 7-repeat non-carriers exhibited increased neural activation of the left middle and inferior frontal gyrus (IFG) in the IC and greater cerebellar activation in the TT. Furthermore, the 7-repeat non-carriers exhibited a stronger coupling in haemodynamic responses between left IFG and the anterior cingulate cortex (ACC) during the IC and between cerebellar activation and brain regions that have high DRD4 density, including the IFG and the ACC during the TT. Our results indicate that the 7-repeat allele influences both regional brain activation patterns as well as connectivity patterns between neural networks of incompatibility and temporal processing.