title: The effects of GRIN2B and DRD4 gene variants on local functional connectivity in attention-deficit/hyperactivity disorder.
abstract: 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.
authors.affiliation: 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.
authors.forename: Johanna Inhyang
authors.initials: JI
authors.lastname: Kim
authors.affiliation: Computational Affective Neuroscience and Development Laboratory, Graduate School of Medical Science and Engineering, KAIST, 291 Daehak-no, Yoosung-gu, Daejeon, 34141, Republic of Korea.
authors.forename: Jae Hyun
authors.initials: JH
authors.lastname: Yoo
authors.affiliation: Computational Affective Neuroscience and Development Laboratory, Graduate School of Medical Science and Engineering, KAIST, 291 Daehak-no, Yoosung-gu, Daejeon, 34141, Republic of Korea.
authors.forename: Dohyun
authors.initials: D
authors.lastname: Kim
authors.affiliation: Computational Affective Neuroscience and Development Laboratory, Graduate School of Medical Science and Engineering, KAIST, 291 Daehak-no, Yoosung-gu, Daejeon, 34141, Republic of Korea. bs.jeong@kaist.ac.kr.|KI for Health Science and Technology, KAIST Institute, 291 Daehak-no, Yoosung-gu, Daejeon, 34141, Republic of Korea. bs.jeong@kaist.ac.kr.
authors.forename: Bumseok
authors.initials: B
authors.lastname: Jeong
authors.affiliation: Division of Child and Adolescent Psychiatry, Department of Psychiatry, Seoul National University College of Medicine, 101 Daehak-no, Chongno-gu, Seoul,, 03080, Republic of Korea. kbn1@snu.ac.kr.
authors.forename: Bung-Nyun
authors.initials: BN
authors.lastname: Kim
mesh_terms: D000293:Adolescent; D000956:Antigens, Viral; D001289:Attention Deficit Disorder with Hyperactivity / Q000000981:diagnostic imaging / Q000235:genetics* / Q000503:physiopathology*; D001921:Brain / Q000000981:diagnostic imaging / Q000503:physiopathology*; D001931:Brain Mapping; D002648:Child; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D009434:Neural Pathways / Q000000981:diagnostic imaging / Q000503:physiopathology; D011110:Polymorphism, Genetic; D050638:Receptors, Dopamine D4 / Q000235:genetics*; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics*; D012146:Rest
chemical_list: D000956:Antigens, Viral; C493599:DRD4 protein, human; C030663:FMR antigen; C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D050638:Receptors, Dopamine D4
keywords: Attention-deficit/hyperactivity disorder; Dopamine receptor; Genetics; Glutamate receptor; Resting state functional MRI