Association Between NRGN Gene Polymorphism And Restingstate Hippocampal Functional Connectivity In Schizophrenia

Objective: Schizophrenia is a group of severe mental disorders whose etiology is not completely clear.Currently,the diagnosis of SZ lacks specific biomarkers.A singlenucleotide polymorphism in the NRGN gene(rs12807809)has been believed to be related to schizophrenia(SZ)based on genome-wide association studies.Moreover,hippocampal dysfunction associated with rs12807809 has been reported.The hippocampus is an important part of the Papez circuit and plays an important role in processes such as learning and memory.In addition,converging evidence suggests hippocampal dysfunction is involved in the pathophysiology of SZ.However,the association between rs12807809 and dysfunction of hippocampus in SZ is unknown and understanding the association is helpful to further elucidate the pathophysiological mechanism of SZ.So,the current study investigates the association between rs12807809 and dysfunction of hippocampus in SZ in order to find the biomarker of SZ and provide new ideas for early detection and diagnosis of diseases.Methods: In this study,blood samples were collected from 52 SZ patients and 82 healthy controls(HC)who met the inclusion criteria,and the NRGN gene rs12807809 genotype was detected.Meanwhile,resting-state functional magnetic resonance imaging(fMRI)was performed.The image data was pre-processed to calculate the voxel-based whole-brain functional connectivity(FC)with the hippocampus as the region of interest.Using chisquare test,two-sample t test and analysis of variance to analysis demographic data of four groups of participants.Analysis of variance of factorial design was used to obtain the main effect of diagnosis and genotype and their interaction with diagnosis(SZ,HC)and genotype(CC/CT,TT)as factors and gender and age as covariates.GRF correction was used to correct the results(voxel P<0.001,P<0.05 after correction).Post hoc two-sample t-test and Bonferroni correction were performed on FC values extracted from the significant brain region,P<0.05.Results: 1.There were no significant differences in gender and age among the four groups,and no significant differences in disease course between the SZ-TT group and the SZCC/CT group.Significant differences in educational and BPRS scores was found among the four groups.The gene frequency of SZ group and HC group were in line with the Hardy-Weinberg equilibrium.2.Significant main effects of diagnosis were observed in FC between the hippocampus and the left lingual gyrus,left fusiform gyrus,left inferior temporal gyrus(corrected P<0.05),compared with HC group,the FC between the hippocampus and the left lingual gyrus,left fusiform gyrus,left inferior temporal gyrus were significantly increased in SZ group.3.No significant main effect of genotype was observed.4.A significant diagnosis by genotype interaction in functional connectivity between the hippocampus and the left anterior cingulate gyrus,as well as the bilateral middle cingulate gyri,was observed,with TT homozygous with SZ showing smaller FC than the connectivity in C-carriers with SZ and TT homozygotes in the healthy control group.Conclusions: 1.Abnormal increased FC between hippocampus and lingual gyrus,fusiform gyrus and inferior temporal gyrus in SZ may be involved in the pathophysiological changes of SZ.2.The NRGN rs12807809 TT genotype may be associated with Papez circuit dysfunction in SZ patients,TT genotype and Papez circuit dysfunction may be involved in the pathophysiology of SZ collectively.