Effects Of DRD4 Rs1800955 Polymorphisms On Resting-state Brain Function And Working Memory In Children With ADHD

Objective: The present study aimed to investigate the effects of the Dopamine Receptor D4 gene(DRD4)rs1800955 single nucleotide polymorphism(SNP)on resting-state brain function in children with attention deficit hyperactivity disorder(ADHD),and further explore the correlation between brain function and working memory,providing a new research direction and theoretical basis for the study of ADHD etiology.Methods: 71 ADHD children who met the inclusion criteria were collected.The polymorphism of DRD4 rs1800955 was detected by polymerase chain reaction(PCR).According to genotyping,it was divided into TT homozygous group and C allele carrying group.The working memory index in Wechsler Intelligence Scale for children-Fourth Edition(WISC-IV)in Chinese version was used to evaluate the working memory ability.Rs-fMRI scanning was performed on ADHD children.The collected brain imaging data were preprocessed,and the brain function indexes of regional homogeneity(Re Ho),fractional amplitude of low-frequency fluctuations(f ALFF)and functional connectivity(FC)were calculated.SPSS 23 software was used to compare the general clinical characteristics and working memory indexes among samples.The statistical analysis module in DPABI was used to compare and analyze brain function indexes,and Gaussian random field(GRF)theory was used for multiple comparison correction(voxel P < 0.001,cluster P < 0.05,bilateral test).Finally,under the control of age and intelligence,the correlation between brain function and working memory was further calculated.Results: There was no significant difference in age,head movement,FSIQ,working memory index,inattention score and hyperactivity impulse score between the two groups(P > 0.05).Compared with C-carriers,TT homozygous ADHD children had reduced Re Ho in the right middle occipital gyrus and increased Re Ho in the right superior frontal gyrus(GRF corrected P <0.05).The right middle occipital gyrus and the right superior frontal gyrus were used as seeds for functional connection.And then compared and analyzed between groups.After comparative analysis between groups,it was found that FC in the right middle occipital gyrus and cerebellum decreased,and FC in the right superior frontal gyrus and angular gyrus decreased in TT homozygous ADHD children(GRF corrected P <0.05).For f ALFF no brain regions with significant differences between the two groups were found after GRF correction.There was no significant correlation between Re Ho value and working memory index in right middle occipital gyrus(TT homozygous: r =-0.066,P = 0.740;C-carriers: r =0.202,P= 0.268),right superior frontal gyrus(TT homozygous: r =-0.122,P = 0.535;C-carriers: r = 0.055,P = 0.763);There was no significant correlation between FC values of right middle occipital gyrus and cerebellum(TT homozygous: r = 0.037,P = 0.851;C-carriers:-0.312,P = 0.082),right superior frontal gyrus and angular gyrus(TT homozygous: r =-0.122,P = 0.535;C-carriers: r =-0.049,P = 0.790)and work memory index;After further calculating the correlation between each group of f ALFF/Re Ho and their working memory,it was found that there was a significant correlation between f ALFF and working memory index in the right precentral gyrus of TT homozygous ADHD children(r= 0.762,P < 0.001),but there was no correlation in the C allele carrier.There was no correlation between Re Ho and working memory index in both groups.Conclusion: DRD4 rs1800955 polymorphism has different effects on regional brain functional activity and functional connectivity in ADHD children.The brain dysfunction of TT homozygous ADHD children is more significant.There is a correlation between f ALFF in the right precentral gyrus and working memory ability of TT homozygous ADHD children.