The dopamine D4 receptor gene (DRD4) has been consistently reported to be associated with attention-deficit/hyperactivity disorder (ADHD). Recent studies have linked DRD4 to functional connectivity among specific brain regions. The current study aimed to compare the effects of the DRD4 genotype on functional integrity in drug-naïve ADHD children and healthy children. Resting-state functional MRI images were acquired from 49 children with ADHD and 37 healthy controls (HCs). We investigated the effects of the 2-repeat allele of DRD4 on brain network connectivity in both groups using a parameter called the degree of centrality (DC), which indexes local functional relationships across the entire brain connectome. A voxel-wise two-way ANCOVA was performed to examine the diagnosis-by-genotype interactions on DC maps. Significant diagnosis-by-genotype interactions with DC were found in the temporal lobe, including the left inferior temporal gyrus (ITG) and bilateral middle temporal gyrus (MTG) (GRF corrected at voxel level p < 0.001 and cluster level p < 0.05, two-tailed). With the further subdivision of the DC network according to anatomical distance, additional brain regions with significant interactions were found in the long-range DC network, including the left superior parietal gyrus (SPG) and right middle frontal gyrus (MFG). The post-hoc pairwise analysis found that altered network centrality related to DRD4 differed according to diagnostic status (p < 0.05). This genetic imaging study suggests that the DRD4 genotype regulates the functional integration of brain networks in children with ADHD and HCs differently. This may have important implications for our understanding of the role of DRD4 in altering functional connectivity in ADHD subjects.

多巴胺 D4 受体基因 (DRD4) 一直被报道与注意力缺陷/多动障碍 (ADHD) 相关。最近的研究将 DRD4 与特定大脑区域之间的功能连接联系起来。目前的研究旨在比较 DRD4 基因型对未用药 ADHD 儿童和健康儿童功能完整性的影响。从 49 名患有多动症的儿童和 37 名健康对照 (HC) 中获取静息状态功能性 MRI 图像。我们使用称为中心度 (DC) 的参数研究了 DRD4 的 2 重复等位基因对两组大脑网络连接的影响，该参数对整个大脑连接组的局部功能关系进行了索引。进行体素双向 ANCOVA 以检查 DC 图上的基因型诊断相互作用。在颞叶发现了显着的基因型诊断与 DC，包括左侧颞下回 (ITG) 和双侧颞中回 (MTG)（在体素水平 p < 0.001 和簇水平 p < 0.05 校正的 GRF，两个尾）。随着根据解剖距离对 DC 网络的进一步细分，在远程 DC 网络中发现了具有显着相互作用的其他大脑区域，包括左顶叶上回 (SPG) 和右额中回 (MFG)。事后成对分析发现，与 DRD4 相关的网络中心性改变因诊断状态而异（p < 0.05）。这项基因成像研究表明，DRD4 基因型对 ADHD 和 HC 患儿大脑网络的功能整合有不同的调节作用。