Abstract
Objective: The present study aimed to investigate the effects of the dopamine receptor D4 (DRD4) −521 C/T single-nucleotide polymorphism on brain function among children with attention deficit hyperactivity disorder (ADHD) and to evaluate whether brain function is associated with behavioral performance among this demographic.Methods: Using regional homogeneity, fractional amplitude low-frequency fluctuation, and functional connectivity as measurement indices, we compared differences in resting-state brain function between 34 boys with ADHD in the TT homozygous group and 37 boys with ADHD in the C-allele carrier group. The Conners' Parent Rating Scale, the SNAP-IV Rating Scale, the Stroop Color Word Test, the go/no-go task, the n-back task, and the working memory index within the Wechsler Intelligence Scale for Children-Fourth Edition were selected as comparative indicators in order to test effects on behavioral performance.Results: We found that TT homozygotes had low behavioral performance as compared with C-allele carriers. The regional homogeneity for TT homozygotes decreased in the right middle occipital gyrus and increased in the right superior frontal gyrus as compared with C-allele carriers. In addition, the right middle occipital gyrus and the right superior frontal gyrus were used as the seeds of functional connectivity, and we found that the functional connectivity between the right middle occipital gyrus and the right cerebellum decreased, as did the functional connectivity between the right superior frontal gyrus and the angular gyrus. No statistically significant differences were observed in the respective brain regions when comparing the fractional amplitudes for low-frequency fluctuation between the two groups. Correlation analyses demonstrated that the fractional amplitude low-frequency fluctuation in the precentral gyrus for TT homozygotes were statistically significantly correlated with working memory.Conclusions: We found differing effects of DRD4 −521 C/T polymorphisms on brain function among boys with ADHD. These findings promote our understanding of the genetic basis for neurobiological differences observed among children with ADHD, but they must be confirmed in larger samples.
Highlights
Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder characterized by age-inappropriate inattention, hyperactivity, and impulsivity [1]
We investigated the effects of the dopamine receptor D4 (DRD4) −521 C/T single-nucleotide polymorphism (SNP) on brain function in boys with ADHD
Considering functional connectivity (FC) based on the right middle occipital gyrus (MOG) as a seed, TT homozygotes had reduced FC in the right MOG and the right cerebellum as compared with the C-allele carriers (Figure 1B; coordinates: 21, −75, −24) (GRF-corrected p < 0.05)
Summary
Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder characterized by age-inappropriate inattention, hyperactivity, and impulsivity [1]. Previous studies have shown that ADHD has high heritability [7]. DRD4 mediates the post-synaptic activity of dopamine and participates in cognitive functions and emotional responses, including attention, perception, planning, language, and memory [9,10,11]. Studies have shown that the DRD4 −521 C/T SNP is associated with specific personality traits [12], novelty seeking, schizophrenia risk [13], cognitive impairment (i.e., speech fluency and working memory) [14], and executive dysfunction [15]. A previous study reported that the transcriptional activity for the T allele in the DRD4 −521 C/T SNP was 40% lower than that of the C allele [16]. The DRD4 −521 C/T SNP has been confirmed to be a critical factor in the pathogenesis of ADHD [17, 21, 22]
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