2.10 THE EFFECT OF GRIN2B AND DRD4 POLYMORPHISMS ON LOCAL FUNCTIONAL CONNECTIVITY IN ATTENTION-DEFICIT/HYPERACTIVITY DISORDER

• Published in: Journal of the American Academy of Child and Adolescent Psychiatry Vol. 55; no. 10; p. S124
• Main Authors: Kim, Johanna I., Yoo, Jaehyun, Jeong, Bumseok, Kim, Bung-Nyun
• Format: Journal Article
• Language: English
• Published: Baltimore Elsevier Inc 01.10.2016; Elsevier BV
• Subjects: Alleles; Attention deficit hyperactivity disorder; Brain; Brain mapping; Child & adolescent psychiatry; Children; Diagnosis; Dopamine; Dopamine D4 receptors; Effects; Functional connectivity; Functional magnetic resonance imaging; Genes; Genetic analysis; Genotype & phenotype; Glutamic acid receptors; Glutamic acid receptors (ionotropic); Hyperactivity; Medical diagnosis; N-Methyl-D-aspartic acid receptors; Neural networks; Neurotransmission; Pediatrics; Polymorphism; Psychiatry; Resting; Test scores
• ISSN: 0890-8567; 1527-5418
• DOI: 10.1016/j.jaac.2016.09.076

Objectives: Genetics studies have identified significant relationships between ADHD and N-methyl-D-aspartate (NMDA) receptor genes. However, phenotypical correlates of brain functions associated with these genes have yet to be investigated. We examined the association of GRIN2B, an NMDA receptor-related gene, and the dopamine receptor D4 (DRD4) gene exon III variable number tandem repeats 2-repeat allele with local functional connectivity in subjects with ADHD and control subjects. Methods: A total of 67 ADHD subjects and 44 control subjects (aged 6-17 years) were recruited from a child and adolescent psychiatric clinic and completed genetic analyses and resting-state fMRI scans. The effects of diagnosis, genotype, and the diagnosis-genotype interaction of the two genetic polymorphisms on the local resting-state functional connectivity using static regional homogeneity (ReHo) and its temporal characteristics, such as dynamic mean and SD, were examined by surface-based analysis. The correlation between the variables of the ReHo analyses showing significant diagnosis-genotype interaction and neuropsychological test scores were examined. Results: There were significant diagnosis (P < 0.001) and interaction (P = 0.02) effects of GRIN2B on static ReHo in the left superior parietal cluster, and the ReHo value was correlated positively with the Children's Color Trails Test interference scores in the ADHD with T allele subgroup (P = 0.012). There also were significant diagnosis (P < 0.001) and interaction (P = 0.03) effects of the DRD4 gene on the dynamic ReHo SD in the right superior parietal cluster. Conclusions: These results suggest that alterations in neurotransmission mediated by glutamate-dopamine interaction in ADHD may contribute to abnormalities in local functional connectivity and its dynamic repertoire.