Serotonin 2A Receptor Gene Polymorphism in Korean Children with Attention-Deficit/Hyperactivity Disorder

Abstract

ObjectiveThe purpose of this study was to investigate the association between the T102C polymorphism in the serotonin 2A receptor gene and attention-deficit/hyperactivity disorder (ADHD) in Korean patients.MethodsA total of 189 Korean children with ADHD as well as both parents of the ADHD children and 150 normal children participated in this study. DNA was extracted from blood samples from all of the subjects, and genotyping was conducted. Based on the allele and genotype information obtained, case-control analyses were performed to compare the ADHD and normal children, and Transmission disequilibrium tests (TDTs) were used for family-based association testing (number of trios=113). Finally, according to the significant finding which was showed in the case-control analyses, the results of behavioral characterastics and neuropsychological test were compared between ADHD children with and without the C allele.ResultsIn the case-control analyses, statistically significant differences were detected in the frequencies of genotypes containing the C allele (χ2=4.73, p=0.030). In the family-based association study, TDTs failed to detect linkage disequilibrium of the T102C polymorphism associated with ADHD children. In the ADHD children, both the mean reaction time and the standard deviation of the reaction time in the auditory continuous performance test were longer in the group with the C allele compared to the group without the C allele.ConclusionThe results of this study suggest that there is a significant genetic association between the T102C polymorphism in the serotonin 2A receptor gene and ADHD in Korean children.

Cortical gradient perturbation in attention deficit hyperactivity disorder correlates with neurotransmitter-, cell type-specific and chromosome- transcriptomic signatures

“…The decreased GABA densities across cortical areas in ADHD could result in interneuronal deficits disrupting brain structural or functional outcomes 46,47,48 , abnormal changes of cortical GABA receptors may shape the connectome gradient, triggering ADHD clinical symptoms. Serotonin is involved in several neurodevelopmental and regulatory functions critically associated with ADHD, and this the link between the gradient dysregulations and cortical 5-HT2A receptor may reflect that: 1) several etiologic risk factors (i.e., T102T/C, 1438A>G of HRT2A) for ADHD could directly determine synthesis of 5-HT2A receptor across cortical areas 49,50,51,52,53 , 2) variations of signaling pathways of 5-HT2A receptor moderate executive functions 54 critically impaired in ADHD, 3) variations in 5-HT signaling mediate the impact of early life stress on emotional regulation and brain architecture 55,56 . As such, enriched distributions of 5-HT2A receptor along with principle gradient changes may reflect molecular-neural dysfunctions for ADHD.…”