ABSTRACT
Objective To explore the changes of whole brain white matter ( WM) structural net-work topological property in patients with schizophrenia (SP) and the associations between WM networks to-pological efficiency and clinical variables in patients. Methods Deterministic tractography was used to con-struct the WM networks of 59 patients with SP ( patients group) and 41 age-, handedness-, and gender-matched healthy controls (HCs),and graph theoretical methods were applied to investigate abnormalities in the global and nodal properties of the WM network in these patients. Partial correlation analysis was used to analyze the relationship between global and nodal properties of the WM network and clinical variables in pa-tients with SP. Results Both the patients with SP and HCs showed small-world organization of the WM net-works. However,compared with HCs,the patients with SP exhibited significant abnormal global topology,in-cluding increased shortest path length ( t=7. 95, P=0. 0001) and decreased global efficiency ( 30. 83 ± 16. 08,8. 25±6. 13,t=-9. 81,P=0. 002),clustering coefficiency (0. 03±0. 01,0. 02±0. 01,t=-4. 48,P=0. 0003),the average clustering coefficiency (t=-8. 28,P=0. 002),the small-worldness (3. 92±0. 79,2. 79 ±0. 56,t=-7. 82,P=0. 001) of their WM structural networks(all P<0. 005,FDR corrected). Further,the patients with SP showed a reduction in nodal efficiency predominately in the cingulate gyrus ( t=-4. 11, P=0. 000),superior occipital gyrus ( t=-6. 05, P=0. 002), superior temporal gyrus ( t=-10. 46, P=0. 001),middle temporal gyrus (t=-10. 38,P=0. 000),thalamus (t=-6. 10,P=0. 000) and putamen ( t=-8. 38,P=0. 000) (P<0. 005,FDR corrected). Partial correlation results showed that there was no signifi-cant correlation between global topological properties,node efficiency and clinical symptoms in patients group (Eglob:r=-0. 14,P=0. 279;Eloc:r=-0. 06,P=0. 628;Lp:r=0. 28,P=0. 031;Cp:r=0. 27,P=0. 043;λ:r=-0. 18,P=0. 166;γ:r=-0. 29,P=0. 026;σ:r=0. 26,P=0. 048;nEglob:r=0. 36,P=0. 005;nEloc:r=0. 02,P=0. 901). Conclusions The patients with SP exhibit the abnormal of whole brain WM structural network topological property and the node efficiencies of cortico-striato-thalamo circuitry are significantly re-duced.
ABSTRACT
Objective To investigate the susceptibility related sites to schizophrenia through whole genome analysis combined with bioinformatics analysis method.Methods The research was carried out by two stages.In the first stage,300 cases of schizophrenia and 300 healthy controls were enrolled,and 5ml pe-ripheral venous blood was drawn to extract genome DNA.After quality control and concentration adjustment by ultraviolet spectrophotometer,equal mass of DNA was mixed into DNA pooling for case group and control group respectively.Genome-Wide Human SNP Array 6.0 chips were used to detect the polymorphism of the SNP.Plink software was used to locate the differential SNP to genes.GSEA was used to analyze the gene to pathway.Ten loci with the smallest P value of screened pathway were chosen as investigated subjects.In the second stage,240 schizophrenias and 200 healthy controls were collected to gain the genome DNA to verity the genotype of the 10 loci.Results Many single nucleotide polymorphism loci which P<9.2×10-8were found in GWAS.The GSEA pathway analysis showed that the axon guidance pathway was significantly related to the incidence of schizophrenia.The distribution of rs4632195 genotypes involved the distribution of among 10 loci(χ2=11.484,P=0.003)and alleles(χ2=8.824,P=0.009)were statistically significant,and T al-lele was susceptibility genes of schizophrenia(OR=1.537,95%CI:1.157-2.203).Conclusion rs4632195 of DCC gene in the axon guidance pathway is associated with schizophrenia,and the T allele is associated with susceptibility to schizophrenia.