Dopamine D4 Receptor Gene Associated with the Frontal-Striatal-Cerebellar Loop in Children with ADHD: A Resting-State fMRI Study

Abstract

Attention deficit hyperactivity disorder (ADHD) is a common childhood neuropsychiatric disorder that has been linked to the dopaminergic system. This study aimed to investigate the effects of regulation of the dopamine D4 receptor (DRD4) on functional brain activity during the resting state in ADHD children using the methods of regional homogeneity (ReHo) and functional connectivity (FC). Resting-state functional magnetic resonance imaging data were analyzed in 49 children with ADHD. All participants were classified as either carriers of the DRD4 4-repeat/4-repeat (4R/4R) allele (n = 30) or the DRD4 2-repeat (2R) allele (n = 19). The results showed that participants with the DRD4 2R allele had decreased ReHo bilaterally in the posterior lobes of the cerebellum, while ReHo was increased in the left angular gyrus. Compared with participants carrying the DRD4 4R/4R allele, those with the DRD4 2R allele showed decreased FC to the left angular gyrus in the left striatum, right inferior frontal gyrus, and bilateral lobes of the cerebellum. The increased FC regions included the left superior frontal gyrus, medial frontal gyrus, and rectus gyrus. These data suggest that the DRD4 polymorphisms are associated with localized brain activity and specific functional connections, including abnormality in the frontal-striatal-cerebellar loop. Our study not only enhances the understanding of the correlation between the cerebellar lobes and ADHD, but also provides an imaging basis for explaining the neural mechanisms underlying ADHD in children.

Temporal Variability–Based Functional Brain Lateralization Study in ADHD

“…In Wang, Hu, Yao, & Jackson’s work (2013), researchers found the right rectus gyrus showed increased amplitude of low frequency fluctuation (ALFF) in ADHD patients. In another study, researchers reported increased FC in rectus gyrus for ADHD patients with DRD2 2R allele (Qian et al, 2018). Taken together, these findings suggested that abnormal activities of the superior frontal gyrus (medial) and rectus gyrus may represent a promising biomarker of ADHD.…”

Positron Emission Tomography in the Inflamed Cerebellum: Addressing Novel Targets among G Protein-Coupled Receptors and Immune Receptors

“…Early radiological approaches with increasingly detailed analysis of inflammatory or degenerative processes of the cerebellum in more recent years included [ 18 F] FDG [ 2 , 17 , 147 , 148 , 149 ] and 15 O measurements or MRI methods [ 17 , 26 , 150 ].…”

Animal models of attention‐deficit hyperactivity disorder (ADHD)

“…Several molecular/genetic studies are performed focusing on a dopaminergic gene, which supports the evident role of dopamine in the pathophysiology of ADHD (Qian et al., 2018; van der Voet et al., 2016). Apart from all studies published in association with genetic factors, no DNA variants have been indisputably demonstrated as contributing to ADHD vulnerability.…”