Neuroscience Bulletin

, Volume 34, Issue 3, pp 497–506 | Cite as

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

  • Andan Qian
  • Xin Wang
  • Huiru Liu
  • Jiejie Tao
  • Jiejie Zhou
  • Qiong Ye
  • Jiance Li
  • Chuang Yang
  • Jingliang Cheng
  • Ke Zhao
  • Meihao Wang
Original Article


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.


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



This work was supported by the Natural Science Foundation of Zhejiang Province, China (No. LY14H180006, LQ18H090009) and the Natural Science Foundation of Jiangsu Province (BK20160142). We thank all the volunteers for their participations.

Conflict of interest

All authors claim that there are no conflicts of interest.


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Copyright information

© Shanghai Institutes for Biological Sciences, CAS and Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  1. 1.Department of RadiologyFirst Affiliated Hospital of Wenzhou Medical UniversityWenzhouChina
  2. 2.Department of PsychiatryWenzhou Medical UniversityWenzhouChina
  3. 3.Department of Mental HealthFirst Affiliated Hospital of Wenzhou Medical UniversityWenzhouChina
  4. 4.Department of RadiologyYancheng First People’s HospitalYanchengChina
  5. 5.Department of RadiologyFirst Affiliated Hospital of Zhengzhou UniversityZhengzhouChina

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