Effect Of NPSR Rs324981 On Regional Gray Matter Volumes In Healthy Young Adults

Objective: A single nucleotide polymorphism(SNP)rs324981,in the neuropeptide S receptor(NPSR)gene,has recently captured much interest due to the risk-increasing effect of T allele for panic disorder.Functional magnetic resonance imaging(f MRI)studies have found the brain functions of the NPSR rs324981 T allele healthy carriers exhibited opposite changing trends in the same brain regions compared to panic disorder NPSR T allele carriers,indicating a compensatory mechanism,which implies brain structural damage in the T allele healthy carriers.But there is hardly any study on the effect of the SNP on brain structure.The objective of the present study aimed at exploring the impact of NPSR rs324981 SNP on regional gray matter volume(GMV)in 1104 healthy young adults by using voxel-based morphometry(VBM)analysis.Subjects and Methods: A total of 1104 healthy right-handed subjects(508 males,596 females;mean age ± SD = 23.8 ± 2.4 years)participated in this study.They finished the Mood and anxiety measurements.After carefully checking the quality of the data,a total of 1094 subjects(502 males and 592 females,mean age ± SD = 23.82 ± 2.35 years)were included in the further analysis.1.Genotyping Subjects were genotyped for NPSR rs324981 A/T SNP.Genomic DNA was isolated from white blood cells with the EZgene TM Blood g DNA Miniprep Kit following standard protocols.NPSR rs324981 in each subject was genotyped using the i PLEX Gold Assay(Sequenom,San Diego,CA)following the manufacturer’s instructions.2.Data acquisition and data preprocessing Magnetic resonance imaging(MRI)scans were performed on two Discovery MR750 scanners(General Electric,Milwaukee,Wisconsin,USA)from two hospitals.Make sure subjects keep stable during scanning.The gray matter(GM)images were obtained by using VBM8 toolbox pipeline in SPM.3.Statistical analysis The subjects were divided into three groups based on the presence of NPSR rs324981 AA,AT or TT genotype.One-way ANCOVA design was performed to assess voxel-wise regional GMV differences among NPSR rs324981 genotypic groups.Age,gender,year of education and scanners were added as nuisance covariates to the design to control for possible impacts of them.Non-parametric approach based on permutation test theory was performed in DPABI to evaluate statistical significance.And the significant brain regions were extracted as regions of interest(ROIs).Then GMV of each ROI was extracted from each participant by DPABI.The post hoc analysis was performed using one-way ANOVA(P < 0.05,Bonferroni corrected)in SPSS for Windows.Result: 1.The results from One-way ANCOVA exhibited regional GMV differences in the right superior temporal gyrus(STG)and left medial prefrontal cortex(m PFC)among the NPSR rs324981 genotypic groups(P < 0.001 uncorrected,cluster size > 50 voxels,5000 permutations).2.Post hoc tests revealed that the more active NPSR rs324981 T allele carriers(AT heterozygotes and TT homozygotes)showed significantly decreased GMV in the right superior temporal gyrus(STG)and left medial prefrontal cortex(m PFC)compared to the AA homozygotes.Conclusion: The GMV of STG and m PFC in the more active NPSR rs324981 T allele carriers exhibit similar changing pattern,which implies these changes could be considered as the early brain structural damage.Neuroimaging studies have proposed that the STG and m PFC are implicated in the pathogenesis of panic disorder via regulating in the processing of interoception and top-down control of emotion,respectively.Our results imply the more active NPSR rs324981 T allele increases the risk for panic disorder might be the outcomes of biased interoceptive processing and insufficient top-down control,caused by the volume reductions in STG and m PFC.