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

【Author】

ANDan Qian;Xin Wang;Huiru Liu;Jiejie Tao;Jiejie Zhou;Qiong Ye;Jiance Li;Chuang Yang;Jingliang Cheng;Ke Zhao;Meihao Wang;Department of Radiology, First Affiliated Hospital of Wenzhou Medical University;Department of Radiology, Yancheng First People's Hospital;Department of Mental Health, First Affiliated Hospital of Wenzhou Medical University;Department of Radiology, First Affiliated Hospital of Zhengzhou University;Department of Psychiatry, Wenzhou Medical University;

【Institution】

Department of Radiology, First Affiliated Hospital of Wenzhou Medical University;Department of Radiology, Yancheng First People's Hospital;Department of Mental Health, First Affiliated Hospital of Wenzhou Medical University;Department of Radiology, First Affiliated Hospital of Zhengzhou University;Department of Psychiatry, Wenzhou Medical University;

【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(Re Ho) 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 DRD44-repeat/4-repeat(4 R/4 R) allele(n = 30) or the DRD42-repeat(2 R) allele(n = 19). The results showed that participants with the DRD4 2 R allele had decreased Re Ho bilaterally in the posterior lobes of the cerebellum, while Re Ho was increased in the left angular gyrus. Compared with participants carrying the DRD4 4 R/4 R allele, those with the DRD4 2 R 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.

【Keywords】

Attention deficit hyperactivity disorder;;Dopamine D4 receptor;;Frontal-striatal-cerebellar loop;;Resting-state functional magnetic resonance imaging;;Regional homogeneity;;Functional connectivity

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