Mental Health and Behavioral Medicine Services for Clinical Departments, Seoul National University Bundang Hospital, 13620, 173 bun-gil 82, Goomi-ro, Bundang-gu, Seongnam, Republic of Korea.
Computational Affective Neuroscience and Development Laboratory, Graduate School of Medical Science and Engineering, KAIST, 291 Daehak-no, Yoosung-gu, Daejeon, 34141, Republic of Korea.
Brain Imaging Behav. 2018 Feb;12(1):247-257. doi: 10.1007/s11682-017-9690-2.
Based on the interplay between dopaminergic and glutamatergic systems, N-Methyl-D-Asparate (NMDA) receptor genes are thought to be involved in the pathophysiology of ADHD. However, the phenotypical correlates of brain functions associated with NMDA receptor genes and dopamine receptor genes in ADHD are yet to be investigated. We examined the diagnosis, genotype and the diagnosis-genotype interaction effects of GRIN2B and DRD4 variants on the local functional connectivity (by using the mean of static regional homogeneity (ReHo) and the mean and standard deviation (SD) of dynamic ReHo) in 67 ADHD subjects and 44 controls (aged 6-17 years). GRIN2B genotypes were divided into the C/C group and T allele carrier group; DRD4 genotypes were divided into the 2R group and non-2R group. The correlation between the ReHo values showing significant diagnosis-genotype interaction and Children's Color Trails Test (CCTT) scores were examined. CCTT measures processing speed, sustained and divided attention. There were significant diagnosis (p < 0.001) and interaction (p = 0.02) effects of the GRIN2B variant on the static ReHo mean in the left superior parietal cluster, and the ReHo value was positively correlated with the CCTT interference score in the ADHD with T allele carrier subgroup (p = 0.012). There were significant diagnosis (p < 0.001) and interaction (p = 0.03) effects of the DRD4 variant on the dynamic ReHo SD in the right superior parietal cluster. These results suggest that alterations in the glutamate and dopamine system in ADHD may contribute to abnormalities in local functional connectivity and its dynamic repertoire in the superior parietal area, and these abnormalities would be related to dysfunction in sustained and divided attention.
基于多巴胺能和谷氨酸能系统的相互作用，N-甲基-D-天冬氨酸（NMDA）受体基因被认为与 ADHD 的病理生理学有关。然而，ADHD 中与 NMDA 受体基因和多巴胺受体基因相关的脑功能的表型相关性尚未得到研究。我们检查了诊断、基因型以及 GRIN2B 和 DRD4 变体对 67 名 ADHD 患者和 44 名对照者（年龄 6-17 岁）局部功能连接（使用静态区域同质性（ReHo）的平均值和动态 ReHo 的平均值和标准差（SD））的诊断-基因型相互作用效应。GRIN2B 基因型分为 C/C 组和 T 等位基因携带者组；DRD4 基因型分为 2R 组和非 2R 组。检查了显示显著诊断-基因型相互作用的 ReHo 值与儿童颜色轨迹测试（CCTT）评分之间的相关性。CCTT 用于测量加工速度、持续性和分散注意力。GRIN2B 变体在左顶叶上簇的静态 ReHo 均值上存在显著的诊断（p<0.001）和相互作用（p=0.02）效应，而 ADHD 中携带 T 等位基因的亚组的 ReHo 值与 CCTT 干扰评分呈正相关（p=0.012）。DRD4 变体在右顶叶上簇的动态 ReHo SD 上存在显著的诊断（p<0.001）和相互作用（p=0.03）效应。这些结果表明，ADHD 中谷氨酸和多巴胺系统的改变可能导致顶叶局部功能连接及其动态变化的异常，而这些异常与持续性和分散注意力的功能障碍有关。
