The alpha-2A-adrenergic receptor gene polymorphism modulates gray matter structural networks, visual memory, and inhibitory cognitive control in children with attention deficit/hyperactivity disorder

The ADRA2A-1291 C > G polymorphism and deficits in visual memory and inhibitory control were associated with attention deficit hyperactivity disorder (ADHD). The present study aimed to examine whether the ADRA2A G/G genotype affected gray matter (GM) networks in ADHD and whether these gene-brain modulations were associated with cognitive function in ADHD. Seventy-five drug-naive ADHD children and 70 healthy controls were recruited. The GM networks were obtained based on areal similarities of GM, and network topological properties were analyzed using graph theory. Visual memory and inhibitory control were assessed by the visual memory test and the Stroop test, respectively. SNP genotyping of rs1800544 was performed. A significant interaction between ADHD diagnosis and gene polymorphism was observed in the nodal degree of the left inferior parietal lobule and left inferior (opercular) frontal gyrus. In the ADHD group, nodal efficiency in the left inferior (orbital) frontal gyrus in ADHD with G/G was lower than that in ADHD without G/G. Moreover, the ADRA2A-modulated alterations in nodal properties were associated with visual memory and inhibitory control. Our findings provide novel gene-brain behavior association evidence that GM network alterations, especially in the frontoparietal loop, were related to visual memory and inhibitory control in ADHD children with ADRA2A-G/G.