The norepinephrine transporter gene modulates functional brain activations in drug-naïve children with attention-deficit/hyperactivity disorder
Journal
European Child and Adolescent Psychiatry
ISSN
1435-165X
Date Issued
2026-04-06
Author(s)
Abstract
The norepinephrine transporter gene (SLC6A2) is implicated in attention-deficit hyperactivity disorder (ADHD), but the neural mechanisms underlying this association remain poorly understood. This study explored whether a SLC6A2 haplotype affected functional brain activations in children with ADHD. We evaluated 109 drug-naïve children with ADHD, including 48 carriers of the SLC6A2 rs36011 (T)/rs1566652 (G) haplotype and 61 non-carriers, and 121 typically developing children (TDC), comprising 64 with and 57 without the TG haplotype. Functional brain activations were measured using the counting Stroop task during functional magnetic resonance imaging. Compared to TDC, children with ADHD exhibited reduced brain activations in the bilateral middle temporal gyri (MTG) and the right postcentral gyrus. Furthermore, the TG haplotype carriers exhibited reduced brain activations in the left anterior cingulate cortex (ACC), inferior frontal gyrus (IFG), and left MTG compared to non-carriers. Significant interactions between the presence of ADHD and the TG haplotype were found in the left ACC, left MTG, and left precuneus, underscoring the synergistic effects of ADHD and genetic factors on brain function. The present study identified significant alterations in brain activations linked to the SLC6A2 genotype in specific brain areas, such as the ACC, IFG, and MTG. The findings enhanced our understanding of the unique impact of the SLC6A2 rs36011 (T)/rs1566652 (G) haplotype on the neurophysiology of individuals with ADHD. Our results highlighted the SLC6A2 genotype’s functional consequences and further elucidated its role in the neurobiological mechanisms of ADHD.
Subjects
Attention-deficit hyperactivity disorder
Imaging genetics
Neuroimaging
Norepinephrine transporter gene
Type
journal article