Association Between Schizophrenia Risk Gene Polymorphism And Brain Imaging Characteristics

Schizophrenia is a severe mental disease with a lifetime prevalence of about 1%,in generally,clinical manifestations are syndromes with complex and variable symptoms.At present,the pathogenesis of schizophrenia is still unknown,research manifested that genetic factor plays a pivotal role in pathogenesis of schizophrenia.Magnetic resonance imaging(MRI),as a non-invasive and high-resolution detection method,has been widely used in the study of mental disease,which can detect brain abnormalities in patients.Based on MRI images,genetic information,and clinical scales of 55 first episode schizophrenia(FES)patients and 53 healthy controls(HC)from the Shanghai Mental Health Center,using the method of medical image processing,statistical analysis and machine learning,this paper explored the modulation effect of schizophrenia risk gene on brain structural and functional characteristics,as well as classified schizophrenia patients and HC based on brain imaging characteristics.This article mainly includes the following three works:Firstly,baesd on structural and functional MRI images,rs6994992 genotype information and cognition scales from 53 healthy subjects,seven structural features were obtained using Free Surfer software,and functional connectivity was obtained using the data processing assistant for resting-state functional magnetic resonance imaging(DPARSF)software.A general linear model was used to determine the effects of risk allele dosage of rs6994992,and Spearman correlation analysis was employed to calculate the correlation between altered brain characteristics and cognition scales.The results demonstrated that regions with significant differences in structural characteristics between genotype groups with different dosages were mainly located in the frontal lobes,temporal lobes,hippocampus and angular gyrus.Significant regions of functional connectivity mostly overlapped with the structural results.The brain regions and functional connectivities with significant differences were significantly correlated with the cognition scales.These results reveal the modulation effect of schizophrenia risk variant rs6994992 on structural and functional characteristics of brain.Secondly,based on structural and functional MRI images,as well as genetic information of 55 FES patients and 53 HC,Free Surfer software was applied to obtain characteristics of whole brain volume,thickness and surface area,DPARSF software and MATLAB script were used to obtain local FCD and global FCD.Using the analysis of covariance to evaluate the main effect of disease and interaction effect,we analysed the main effect of disease and the interaction effect between disease and genotype of 5-hydroxytryptamine 2A receptor(5-HT2A)and dopamine D3 receptor(DRD3)gene on cortical morphology and FCD.The results of disease main effect suggested that brain regions with significant differences in local FCD and global FCD were mainly located in functional hub regions.The significant interaction effects of disease and the polymorphism of 5-HT2A and DRD3 genes on brain structural and functional characteristics were mainly located in the temporal cortex.These important findings reveal intrinsic relationship between 5-HT2A and DRD3 gene and schizophrenia pathogenesis.Thirdly,based on structural and functional MRI images from 55 FES patients and 53 HC,voxel-based morphometry analysis was applied to acquire grey matter volume,DPARSF software and MATLAB script were used to obtain global FCD.Univariate analysis(two-sample t-test)was employed to detect the differences between groups for the preliminary feature screening.Support vector machine was used to classify schizophrenia patients and HC.The results show that using the abnormal gray matter volume and global FCD characteristics as the input of classifier can obtain good classification outcomes,with the accuracy of 84.47% and 82.52%,respectively.The weight maps show that the voxels with high weight values in the gray matter volume are mainly located in the frontal lobe cortex,and the voxels with high weight values in the global FCD are mainly located in the temporal lobe cortex.The accuracy of classifier obtained in this study is basically the same as the accuracy reported in MRI studies of schizophrenia.The modulation effects of schizophrenic candidate genes on brain structure and function obtained in this paper provide supporting evidence for the genetic role of these candidate genes in schizophrenia and help to understand the etiology and pathological mechanisms of schizophrenia.The results of classification study offer a referred imaging characteristics for clinical diagnosis of schizophrenia.These important findings are helpful for subsequent research.