Correlation Between White Matter Integrity And Plasma Leptin Levels In Schizophrenia And Genetically High-Risk Individuals

Objective: Alterations of white matter(WM)integrity have been observed in both schizoprenia(SZ)and individuals at genetic high risk for SZ(GHR-SZ);however,the molecular mechanisms underlying WM disruption remain unclear.Plasma Leptin,as important molecular messengers in brain signaling,which are closely related to neurogenesis in the brain.Emerging evidence implicates that the abnormalities of WM integrity and plasma leptin levels are closely related to the pathogenesis and genetic susceptibility of SZ.In this study,diffusion tensor imaging(DTI)and a multiplex liquidchip assay based on the Luminex platform(Bioplex technology)were used to study SZ and GHR-SZ at the level of neuroimaging and molecular level,to identify abnormalities in WM integrity,plasma leptin levels,and their association in SZ and GHR-SZ individuals.To further improve the understanding of the neuropathophysiological mechanism of SZ and provide new ideas for the early diagnosis and accurate treatment of SZ.Methods: We recruited 126 SZ,99 GHR-SZ and 130 HC matched by gender,age and education years.This subject,aged between 13 and 30 years old.Their informed consent was obtained before the study began.The demographic and clinical information of all subjects were collected,and the clinical symptoms were measured with Brief Psychiatric Rating Scale(BPRS)was assessed,and all participants underwent DTI,in which 113 subjects(34 SZ patients,34 GHR-SZ and 45 HC)collected blood samples within 24 h of imaging.We used SPSS 22.0 and Matlab software packages for statistical analysis based on the collected demographic data,clinical scale data,image data,and blood samples data.The statistical analysis of the data has four parts:(1)Descriptive analysis,variance analysis,and chi square test were used to determine whether there were statistical differences in demographic data and clinical scale data among the three groups of SZ,GHR SZ and HC;(2)The image data obtained by MRI scanning were statistically analyzed by voxel-based analysis method.Three-group(SZ,GHR-SZ,and HC)analyses of FA values were performed in SPM8 using variance analysis(ANCOVA)with diagnostic group as an independent factor,and age and gender as covariates.Group differences were considered significant for P values less than 0.001(corrected,Gaussian random field [GRF] correction)and an extent threshold of 55 voxels.After that,regions of the brain with significant differences between the three groups were evaluated to obtain fractional anisotropy(FA)and Post hoc analysis was used to compare the two afterwards.Using Bonferroni correction,the correction test level is 0.05/3= 0.017,P<0.017 has statistical difference;(3)ANCOVAs were used to compare plasma leptin data between the SZ,GHR-SZ,and HC groups as an independent factor and age and gender as covariates.Post hoc analysis was performed on leptin with significant differences between the three groups(Bonferroni correction,P<0.017);(4)Partial correlation analyses(two-tailed)were performed in the SZ and GHRSZ individuals to explore the relationships between FA values and leptin levels.Results: 1.Results of WM integrity analysis: ANCOVA showed that there were significant differences in FA between the three groups the genu of the corpus callosum(GCC),the body of the corpus callosum(BCC),the splenium of the corpus callosum(SCC),left/right anterior corona radiata(ACR-L/R),left/right posterior corona radiata(PCR-L/R),left/right anterior limb of the internal capsule(ALIC-L/R),left/right posterior thalamic radiation(PTR-L/R),left/right external capsule(EC-L/R),right posterior limb of the internal capsule(PLIC-R),left superior fronto-occipital fasciculus(SFO-L),and fornix(FX)(P<0.001,GRF correction);Post Hoc analysis showed that compared to GHR-SZ and HCs,the SZ group exhibited significantly decreased FA in the GCC,BCC,ACR-L/R,ALIC-L/R,PLIC-R,EC-L/R,SFO,and FX(P < 0.017,Bonferroni corrected).Compared with HCs,the SZ and GHR-SZ individuals had significantly decreased FA in the SCC,PCR-L/R,and PTR-L/R(P<0.017,Bonferroni corrected);2.Results of plasma leptin level analysis: ANCOVA showed that there were significant differences in plasma leptin levels among SZ,GHR-SZ and HC groups,and Post Hoc analysis showed that compared with HC group,the plasma leptin levels of SZ and GHR-SZ groups were increased significantly(P<0.017,Bonferroni correction);3.Results of correlation analysis showed: in SZ group and GHR-SZ group,the FA values of SCC,PCR-L/R,and PTR-L/R were negatively correlated with the plasma leptin level(r=-0.296,P= 0.016)(r=-0.265,P=0.032).Conclusion: 1.Only in the SZ group,the abnormalities of WM fibers such as the GCC,BCC,indicating that the changes of these areas are related to the occurrence and state of SZ,that is,the state brain alterations;2.In SZ group and GHR-SZ group,the abnormalities of WM fibers such as the ACC,indicating that the changes of these areas are related to the heredity of SZ,that is,the quality brain alterations;3.In SZ and GHR-SZ group,the level of plasma leptin was increased,and the change of plasma leptin level was related to the integrity change of WM,and played an important role in the mechanism of pathophysiology of SZ.