Association Analysis Among SNAP25 MnlⅠ Polymorphisms And Resting-state Brain Function,Working Memory In Children With ADHD

Objective: This study aimed to explore the effect of synaptosomal-associated protein 25gene(SNAP25)Mnl1 single nucleotide polymorphism(SNP)on resting state functional magnetic resonance imaging(RS-f MRI)in male children with attention deficit hyperactivity disorder(ADHD).The correlation between functional integration and working memory was further explored.Methods: Fifty-six Children with ADHD who met the inclusion criteria were tested by the Chinese version of Wechsler Intelligence Scale for Child-Fourth Edition(WISC-IV),and the digital span test was used as an indicator of working memory ability.SNAP25Mnl1 SNP was detected by polymerase chain reaction(PCR).According to their genotyping,the subjects were divided into TT homozygous group and G-allele carrier group.RS-f MRI data of the subjects were collected,and DPARSF based on Matlab platform was used to process and analyze the data.The functional integration of brain spontaneous activity of the subjects was calculated based on sliding time window method,and the comparison between samples was made.The correlation between working memory scores and brain functional integration was further calculated.The Alpha Sim program in DPARSF was used for multiple comparison corrections(uncorrected P<0.001,Alpha Sim corrected P<0.01).Results: Among the 56 subjects,1 was excluded because of not meeting the requirements of head movement,and the remaining 55 subjects were grouped according to their genotype.There was no showed no statistical significance in the distribution range of age,full scale IQ,digit memory span scores and head movement(P>0.05).In ADHD patients,compared with the G-allele carriers,the TT homozygous showed significantly decreased voxel-wise concordance of spontaneous brain activity in the right middle frontal gyrus,anterior central gyrus,posterior central gyrus and parietal lobe(Alpha Sim corrected cluster>21),and there was no statistically significant difference between the TT homozygous and the G-allele carriers in volume-wise concordance(t=-0.891,P= 0.378).There were no significant correlations between the voxel-wise concordance of spontaneous brain activity in the right middle frontal gyrus(G-allele carriers: r = 0.556,P=0.254;TT homozygous: r = 0.248,P=0.754),the right posterior central gyrus-parietal lobe-precentral gyrus(G-allele carriers: r = 0.582,P=0.470;TT homozygous: r = 0.342,P=0.572)and working memory ability.There was a significant positive correlation between the voxel-wise concordance of RS-f MRI indicators and digital span scores of TT homozygous ADHD patients in the left superior frontal gyrus(Alpha Sim corrected cluster>23)(r = 0.410,P=0.002),and negative correlations in the left medial prefrontal cortex(r =-0.556,P <0.001),bilateral precuneus(r =-0.499,P <0.001),left occipital cortex(r =-0.440,P =0.001),right occipital cortex(r=-0.514,P<0.001).There was no significant correlation between the voxel-wise concordance of the whole brain and digital memory span score in G-allele carriers.There was no statistically significant difference between the volume-wise concordance of RS-f MRI indicators and digital memory span scores of ADHD patients(G-allele carriers: r=-0.273,P =0.459;TT homozygous: r=-0.148,P =0.286).Conclusion: SNAP25 Mnl1 SNP affects the functional integration of brain spontaneous activity in ADHD patients.The Mnl1 TT homozygous showed a lower ability of brain functional integration.Functional integration of brain spontaneous activity is correlated with working memory ability in Mnl1 TT homozygous ADHD patients.