Effects of SLC6A2 Gene on Brain Activations in Youths with Attention Deficit Hyperactivity Disorder
Poster No:
330
Submission Type:
Abstract Submission
Authors:
Chi-Yung Shang1, Li-Ying Fan2, Tai-Li Chou3, Susan Shur-Fen Gau4
Institutions:
1National Taiwan University Hospital, Taipei, Taiwan, 2Department of Education, National Taipei University of Education, Taipei, Taiwan, 3Department of Psychology, National Taiwan University, Taipei, Taiwan, 4National Taiwan University College of Medicine, Taipei, Taiwan
First Author:
Co-Author(s):
Introduction:
Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder with high heritability. A lot of molecular studies have explored the candidate genes for the pathogenesis of ADHD. Since the pathophysiology of ADHD involve the neurotransmitters of dopamine and norepinephrine (Xing et al., 2016), the norepinephrine transporter gene (SLC6A2) is a promising candidate gene for ADHD. For example, our previous work has shown associations of ADHD with the rs36011 (T)/rs1566652 (G) haplotype of the SLC6A2 gene (Shang et al., 2015). However, the specific neurobiological mechanism of the SLC6A2 rs36011 (T)/rs1566652 (G) haplotype for the pathogenesis ADHD still needs to be explored. Given that the neurotransmitter of norepinephrine has been found to involve in the performance on the counting Stroop task in patients with ADHD (Fan et al., 2017), the current study was to investigate the functional brain effects of the rs36011 (T)/rs1566652 (G) haplotype of the SLC6A2 gene during a counting Stroop task in ADHD children.
Methods:
The present study recruited 109 drug-naïve children aged 7–16, with a clinical diagnosis of ADHD. Besides, we recruited 121 typically developing children (TDC) from similar school districts as those participants with ADHD. We employed matrix-assisted laser desorption/ionization time of flight mass spectrometry to conduct genotyping of rs36011 and rs1566652 of SLC6A2 in the blood samples of all the 230 participants. The participants were divided into four groups according to the presence of the ADHD diagnosis and the rs36011 (T)/rs1566652 (G) haplotype, including ADHD-TG, ADHD-NonTG, TDC-TG, and TDC-NonTG. The counting Stroop task was used to explore the brain activations associated with rs36011 (T)/rs1566652 (G) haplotype of SLC6A2. The experimental stimuli of the counting Stroop task were divided into three distinct conditions, including congruent, incongruent and control conditions. To explore the effects of the SLC6A2 TG haplotype and ADHD, we perform a two-way ANOVA with sex, age, and FIQ as nuisance covariates. The significant functional activations are corrected at the voxel level of family-wise error of p < 0.05.
Results:
All the participants were classified into four groups, including ADHD-TG (n = 48), ADHD-NonTG (n = 61), TDC-TG (n = 64), and TDC-NonTG (n = 57). In group comparisons of the incongruent versus control condition, we found that the ADHD group had lower activation in the right postcentral gyrus and bilateral middle temporal gyri (MTG) than the TDC group. The rs36011 (T)/rs1566652 (G) haplotype carriers demonstrated lower activations in the left MTG, left inferior frontal gyrus (IFG), and the left anterior cingulate cortex (ACC) than those without the TG haplotype (Figure 1). Compared with the ADHD-NonTG group, the ADHD-TG group showed lower brain activations in the left paracentral lobule and bilateral precuneus. Compared with the TDC-TG group, the ADHD-TG group showed lower brain activations in the left precuneus. Besides, we found significant interactions of the rs36011 (T)/rs1566652 (G) haplotype with the diagnosis of ADHD in the left precuneus, the left MTG, and the left ACC (Figure 2).
Conclusions:
The present study was the first to explore the effects of the TG haplotype on the brain activations during the counting Stroop task in drug-naïve children with ADHD. The results demonstrated that the rs36011 (T)/rs1566652 (G) haplotype of SLC6A2 had interaction effects with the diagnosis of ADHD on functional activations in the left precuneus, the left MTG, and the left ACC. Our findings suggested that the rs36011 (T)/rs1566652 (G) haplotype of SLC6A2 could play a crucial role in the modulations of functional brain activations during the counting Stroop task in patients with ADHD. Our imaging genetic study would enhance the understanding of the gene-brain-behavior interactions associated with the pathogenesis of ADHD.
Disorders of the Nervous System:
Neurodevelopmental/ Early Life (eg. ADHD, autism) 1
Genetics:
Genetic Association Studies 2
Keywords:
Attention Deficit Disorder
Cognition
FUNCTIONAL MRI
Norpinephrine
1|2Indicates the priority used for review
·Figure 1. Main effects of the TG haplotype on brain activations for the incongruent versus control condition.
·Figure 2. Effects of interaction of ADHD × TG haplotype on brain activations for the incongruent versus control condition.
Provide references using author date format
Shang, C. Y. (2015). 'A haplotype of the norepinephrine transporter gene (SLC6A2) is associated with visual memory in attention-deficit/hyperactivity disorder.' Progress in Neuro-Psychopharmacology & Biological Psychiatry, vol 58, pp. 89-96.
Xing, B. (2016). 'Norepinephrine versus dopamine and their interaction in modulating synaptic function in the prefrontal cortex.' Brain Research, vol. 1641, pp. 217-233.