1.Graph Neural Networks and Multimodal DTI Features for Schizophrenia Classification: Insights from Brain Network Analysis and Gene Expression.
Jingjing GAO ; Heping TANG ; Zhengning WANG ; Yanling LI ; Na LUO ; Ming SONG ; Sangma XIE ; Weiyang SHI ; Hao YAN ; Lin LU ; Jun YAN ; Peng LI ; Yuqing SONG ; Jun CHEN ; Yunchun CHEN ; Huaning WANG ; Wenming LIU ; Zhigang LI ; Hua GUO ; Ping WAN ; Luxian LV ; Yongfeng YANG ; Huiling WANG ; Hongxing ZHANG ; Huawang WU ; Yuping NING ; Dai ZHANG ; Tianzi JIANG
Neuroscience Bulletin 2025;41(6):933-950
Schizophrenia (SZ) stands as a severe psychiatric disorder. This study applied diffusion tensor imaging (DTI) data in conjunction with graph neural networks to distinguish SZ patients from normal controls (NCs) and showcases the superior performance of a graph neural network integrating combined fractional anisotropy and fiber number brain network features, achieving an accuracy of 73.79% in distinguishing SZ patients from NCs. Beyond mere discrimination, our study delved deeper into the advantages of utilizing white matter brain network features for identifying SZ patients through interpretable model analysis and gene expression analysis. These analyses uncovered intricate interrelationships between brain imaging markers and genetic biomarkers, providing novel insights into the neuropathological basis of SZ. In summary, our findings underscore the potential of graph neural networks applied to multimodal DTI data for enhancing SZ detection through an integrated analysis of neuroimaging and genetic features.
Humans
;
Schizophrenia/pathology*
;
Diffusion Tensor Imaging/methods*
;
Male
;
Female
;
Adult
;
Brain/metabolism*
;
Young Adult
;
Middle Aged
;
White Matter/pathology*
;
Gene Expression
;
Nerve Net/diagnostic imaging*
;
Graph Neural Networks
2.Correlation between functional striatal abnormalities scores and symptoms and cognitive function in patients with schizophrenia
Zheng LI ; Qing LIU ; Xiaoge GUO ; Xiujuan WANG ; Xi SU ; Yongfeng YANG ; Wenqiang LI ; Luxian LYU
Journal of Xinxiang Medical College 2024;41(7):640-644
Objective To explore the correlation between functional striatal abnormalities(FSA)scores and symptoms and cognitive function in patients with schizophrenia.Methods A total of 92 patients with schizophrenia admitted to the Second Affiliated Hospital of Xinxiang Medical University from July 2021 to February 2022 were selected as the research subjects,15 patients were excluded due to excessive interference with head movement during image data analysis,and 77 patients were finally included in the statistical analysis.The cognitive function of the patients before treatment and after 8 weeks of treatment was evaluated through a set of cognitive function tests.The severity of symptoms before treatment and after 8 weeks of treatment was evaluated according to the positive and negative symptom scale(PANSS).The patients were divided into the ineffective group(PANSS<50%,n=33)and the effective group(PANSS ≥ 50%,n=44)according to the PANSS reduction rate.Before treatment and 8 weeks after treatment,the resting-state functional magnetic resonance imaging scans were performed,and FSA scores were calculated.Results There was no significant difference in FSA scores of patients between the effective group and the ineffective group before treatment(P>0.05).After 8 weeks of treatment,the FSA scores of patients in the two groups were significantly higher than those before treatment(P<0.05).After 8 weeks of treatment,there was no significant difference in FSA scores of patients between the effective group and the ineffective group(P>0.05).Before treatment and after 8 weeks of treatment,there was no significant correlation between the FSA scores and the total PANSS scores,positive factor scores,negative factor scores and pathological factor scores in the two groups(P>0.05).There was no significant corre-lation between the pre-treatment FSA scores and the differences in positive factor scores,negative factor scores and pathological factor scores before and after treatment in both groups(P>0.05).In the effective group,the FSA score was significantly nega-tively correlated with the spatial span score(P<0.05)and significantly positively correlated with the category fluency score(P<0.05)before treatment;however,there was no significant correlation between the pre-treatment FSA score and the scores of trail making,symbol coding,word learning,maze solving,visuospatial memory,2-digit continuous performance,3-digit continuous performance and 4-digit continuous performance(P>0.05).In the ineffective group,there was a significant negative correlation between the pre-treatment FSA score and the spatial span and 4-digit continuous performance scores(P<0.05),while there was no significant correlation between the pre-treatment FSA score and the scores of trail making,symbol coding,word learning,maze solving,visuospatial memory,category fluency,2-digit continuous performance and 3-digit continuous performance(P>0.05).There was no significant correlation between the FSA score and cognitive function scores after treat-ment in the effective group(P>0.05).There was a significant positive correlation between the FSA score and the trail making score after treatment in the ineffective group(P<0.05),but there was no significant correlation between the FSA score and the scores of symbol coding,word learning,spatial span,maze solving,visuospatial memory,category fluency,2-digit continuous performance,3-digit continuous performance and 4-digit continuous performance(P>0.05).Conclusion FSA scores in patients with schizophrenia increase significantly after treatment.FSA scores may not be related to the severity of symptoms or treatment response,but are correlated with the cognitive function of information processing speed.
3.Role of histone deacetylase in the sensory gating impairment of offspring during puberty caused by immune activation in pregnant rats
Guanyu WANG ; Senqi LIU ; Yongfeng YANG ; Wenqiang LI ; Luxian LYU ; Xi SU
Journal of Xinxiang Medical College 2024;41(2):101-108
Objective To investigate the expression of histone deacetylase(HDAC)isoforms in the frontal lobe,hippo-campus and liver of offspring rats delivered by rats with maternal immune activation and their correlation with the efficiency of prepulse inhibition(PPI%).Methods Ten pregnant Sprague-Dawley rats were randomly divided into the model group(n=5)and control group(n=5).The rats in the model group were injected with 10 mg·kg-1 polyinosinic-polycytidylic acid(Poly I:C)via the caudal vein on the 9th day of pregnancy,while rats in the control group were given the same volume of sterile physiological saline.After 3 h,blood was collected from the caudal vein,and the levels of interleukin(IL)-1 β,IL-6 and tumor necrosis factor-α(TNF-α)in the plasma of pregnant rats were detected by enzyme-linked immunosorbent assay to evaluate the immune activation status.The pregnant rats in the two groups were fed until natural delivery,the offspring rats were weaned on the 21st day after birth,and the male offspring rats were fed continuously.A prepulse inhibition test was performed at puberty(the 40th day after birth)to evaluate the spatial recognition memory and sensory gating function of the offspring rats.The expression levels of the HDAC gene family in the hippocampus,frontal lobe and liver of offspring rats were detected by real-time fluorescence quantitative polymerase chain reaction.Results The plasma IL-6,IL-1 β and TNF-α levels in the model group were significantly higher than those in the control group(P<0.05).When the prepulse stimulation was 75 dB,the PPI%of the offspring rats at puberty in the model group was significantly lower than that in the control group(P<0.05).When the prepulse stimulation was 80 and 85 dB,there was no significant difference in PPI%between the model group and the control group(P>0.05).In the frontal lobe,the expression levels of HDAC3,HDAC4,HDAC8,HDAC9,HDAC10 and Sirt mRNA in the offspring rats in the model group were significantly lower than those in the control group(P<0.05),while the expression level of HDAC5 mRNA was significantly higher than that in the control group(P<0.05);there were no significant differences in the expression levels of HDAC1,HDAC2,HDAC6,HDAC7 and HDAC11 mRNA between the model group and the control group(P>0.05).In the hippocampus,the offspring rats in the model group had significantly lower expression levels of HDAC1,HDAC8 and HDAC10 mRNA and significantly higher expression levels of HDAC2 and HDAC5 mRNA than those in the control group(P<0.05);there were no significant differences in the expression levels of HDAC3,HDAC4,HDAC6,HDAC7,HDAC9,HDAC11 and Sirt mRNA between the model group and control group(P>0.05).In the liver tissue,the expression levels of HDAC6 and HDAC10 mRNA of the offspring rats in the model group were significantly lower than those in the control group(P<0.05);there were no significant differences in the expression levels of HDAC1,HDAC2,HDAC3,HDAC4,HDAC5,HDAC7,HDAC8,HDAC9,HDAC11 and Sirt mRNA between the model group and the control group(P>0.05).The expression level of HDAC2 mRNA in the hippocampus of offspring rats in the two groups was negatively correlated with PPI%at 75 dB(r=-0.965,P<0.05),the expression levels of HDAC10 and Sirt mRNA in frontal lobe tissues were positively correlated with PPI%at 75dB(r=0.946,0.925;P<0.05).Conclusion Pregnancy Poly I:C infection has significant effects on the expression of HDAC family proteins in offspring rats,and which is related to the impairment of early sensory gating,this may provide new ideas for the research in pathogenesis and drug treatment of schizophrenia.
4.Association of N-cadherin (CDH2) polymorphisms with schizophrenia susceptibility and clinical symptoms in Han Chinese population
Changle ZHAO ; Xi SU ; Yongfeng YANG ; Meng SONG ; Minglong SHAO ; Yan ZHANG ; Luxian LYU ; Wenqiang LI
Chinese Journal of Behavioral Medicine and Brain Science 2022;31(12):1080-1085
Objective:A case-control association analysis was performed to investigate if the single nucleotide polymorphisms (SNPs) of N-cadherin(CDH2) gene is implicated in schizophrenia in a Han Chinese population.Methods:A total of 528 patients with paranoid schizophrenia and 528 healthy controls were recruited from northern Henan province to analyze 25 SNPs located in CDH2 gene.The clinical symptoms of 267 first-episode schizophrenia patients were evaluated with positive and negative syndrome scale (PANSS), and the correlation between CDH2 gene and clinical symptoms was analyzed by SNPStats software online.Results:Allele frequencies of rs9951577 and rs1231268 were significantly correlated with schizophrenia( P<0.05), genotype frequency of rs1639387 was significantly correlated with schizophrenia( P=0.044). After gender classification, SNPs rs1789470 and rs28365328 were found to be significantly correlated with schizophrenia in female patients ( P=0.044, 0.019). In addition, the study found that CDH2 was correlated with the clinical characteristics of schizophrenia( P<0.05), and the negative factor score of patients between GG type rs1231268 and the other two genotypes (AG+ AA) ((21.12±8.41) vs (18.87±7.52)) was statistically significant ( P<0.05). Conclusion:CDH2 gene may be one of the susceptibility genes to SZ, and has definite correlation with clinical negative symptoms.
5.The characteristics of degree centrality and voxel-mirrored homotopic connectivity in patients with obsessive-compulsive disorder
Wenjing TONG ; Xianrui LI ; Haisan ZHANG ; Yongfeng YANG ; Kun LI ; Meng ZHANG ; Bi WANG ; Siyuan LI ; Luxian LYU ; Hongxing ZHANG
Chinese Journal of Behavioral Medicine and Brain Science 2020;29(5):442-447
Objective:To explore the functional connections of the whole brain and the two hemispheres in patients with obsessive-compulsive disorder (OCD).Methods:Twenty-six patients with obsessive-compulsive disorder(patients group) and thirty-seven healthy controls matched in gender, age and education(control group) were enrolled.All the participants accepted the resting-state functional magnetic resonance (rs-fMRI) scan.Based on DPABI and REST software, degree centrality (DC) and voxel - mirrored homotopic connectivity (VMHC) approaches were used to explore the pattern of functional connection in OCD.Results:Compared with the control group, the DC values in the right posterior cerebellar lobe(MNI: x, y, z=45, -87, -12), left precentral gyrus(MNI: x, y, z=-54, 9, 39), left inferior parietal lobule(MNI: x, y, z=-48, -51, 42), right anterior cingulate cortex(MNI: x, y, z=3, 18, 48) were significantly higher( t values were 5.75, 5.26, 5.28 and 5.16, respectively), and the DC values in the left inferior frontal gyrus(MNI: x, y, z=-36, 9, 30) were significantly lower( t value was -6.65) in patients group.The VMHC values in bilateral posterior cerebellar lobe(MNI: x, y, z=±51, -69, -33), bilateral inferior parietal lobule(MNI: x, y, z=±48, -51, 54), bilateral anterior cingulate cortex(MNI: x, y, z=±3, 21, 45)in patients group were significantly higher that those in control group( t values were 5.19, 5.19, 5.02, 5.02, 5.15 and 5.15, respectively). The DC and VMHC values in patients group were not significantly correlated with clinical symptoms(-0.23< r<0.19, P>0.05). Conclusion:OCD patients have abnormal connections between key brain network nodes and relevant brain regions, and functional connections have increased among multiple cerebral hemispheres.
6.The correlation between the volume of brain white matter and cognitive function in childhood and adolescence-onset schizophrenia
Jinghua GUO ; Zhishuang YI ; Luxian LYU ; Suqin GUO ; Yinghui LIANG ; Yanhong XIA ; Rongrong SHAO ; Yuling LI
Chinese Journal of Behavioral Medicine and Brain Science 2019;28(1):54-58
Objective To investigate the relationship between brain white matter volume (WMV) and cognitive function (CF) in childhood and adolescence-onset schizophrenia (CAOS).Methods Forty childhood and adolescence-onset first-episode schizophrenia patients (case group) and thirty-nine healthy volunteers (control group) were selected.All subjects underwent a 3.0 T magnetic resonance imaging(MRI) scans for data acquisition.The Chinese version of MATRICS consensus cognitive battery(MCCB) was used to assess the cognitive function.The psychiatric symptoms of schizophrenia were assessed with the positive and negative syndrome scale (PANSS).And t test was applied to compare whether there were differences in WMV,CF between the two groups.Pearson correlation analysis was used to analyze whether the differences were related with cognitive function and mental symptoms.Results Compared with healthy controls,the case group exhibited WMV deficits in the region of left frontal lobe (LFL) (MNI:x =-27,y =12,z =21),right side limbic lobe (RSLL) (MNI:x =18,y =-9,z =39) and left cingulate gyrus (LCG) (MNI:x =-21,y =-18,z=45) (P<0.05).The WMV of LFL was negatively related with the total score (r=-0.344,P<0.05) and the WMV of LCG was negatively related with the positive symptoms score (r=-0.326,P<0.05) and total score (r=-0.348,P<0.05) of the PANSS.Besides,compared with the controls,the patients showed significant increase in the scores of Trail Making Test (t =3.56,P< 0.01),while significant decrease in the scores of the HVLT-R and BVMT-R(t=-5.67,-8.66,P<0.05).The WMV of RSLL was positively correlated with verbal fluency test in the case group (r=0.40,P<0.05).Conclusion CAOS patients exist multiple reduced WMV and cognitive impairment,suggesting the importance of the WMV abnormalities in the pathophysiological mechanism of cognitive impairment.
7.Changes in the amplitude of low-frequency fluctuation and functional connectivity of resting fMRI in patients with obsessive-compulsive disorder.
Yanli SHI ; Kun LI ; Haisan ZHANG ; Yongfeng YANG ; Yanna KOU ; Meng ZHANG ; Luxian LV ; Hongxing. ZHANG
Chinese Journal of Nervous and Mental Diseases 2019;45(4):217-222
Objective To investigate the spontaneous activity of brain neurons in patients with obsessive-compulsive disorder (OCD) under resting state. Methods Forty-eight OCD patients and 50 age-, gender- and year of education-matched normal controls were enrolled. All the subjects underwent 3.0 T fMRI to acquire resting state brain image. The brain regions with significant differences in amplitude of low-frequency fluctuation (ALFF) between patients and controls were analyzed. Whole-brain functional connectivity (FC) were analyzed using the brain regions with significant differences as seed points, and the correlation between brain regions with significant differences in ALFF and FC analysis and obsessive-compulsive symptoms was analyzed. Results Compared to the control group, the ALFF of left dorsolateral prefrontal cortex increased in patients with OCD (t=4.305, P<0.001). Compared to the controls, the analysis of whole-brain FC (based on MNI template) with the left dorsolateral prefrontal cortex as the regions of interest showed that the FC strength between the left dorsolateral prefrontal cortex and right orbital inferior frontal cortex (t=3.897, P<0.001), left anterior cingulate cortex (t=3.370, P<0.001), right anterior cingulate cortex (t=4.299, P<0.001), left middle cingulate cortex (t=3.220, P<0.001), right middle cingulate cortex (t=4.607, P<0.001) enhanced; the FC strength between the left dorsolateral prefrontal cortex and the left opercular part of inferior frontal gyrus (t=-4.630, P<0.001) weakened in patients with OCD. The FC between the left dorsolateral prefrontal cortex and the left opercular part of inferior frontal gyrus was negatively correlated with obsessions score(r=-0.369, P=0.014), compulsions score (r=-0.392, P=0.009) and total score (r=-0.393, P=0.008) of the Yale-Brown obsessive compulsive scale (Y-BOCS). Conclusion In patients with OCD, spontaneous neural activity of the left dorsolateral prefrontal cortex is enhanced in resting state, and the FC with multiple brain regions is abnormal. The FC strength between the left dorsolateral prefrontal cortex and the left opercular part of inferior frontal gyrus is associated with obsessive-compulsive symptoms.
8.Interaction Between Variations in Dopamine D2 and Serotonin 2A Receptor is Associated with Short-Term Response to Antipsychotics in Schizophrenia.
Liansheng ZHAO ; Huijuan WANG ; Yamin ZHANG ; Jinxue WEI ; Peiyan NI ; Hongyan REN ; Gang LI ; Qiang WANG ; Gavin P REYNOLDS ; Weihua YUE ; Wei DENG ; Hao YAN ; Liwen TAN ; Qi CHEN ; Guigang YANG ; Tianlan LU ; Lifang WANG ; Fuquan ZHANG ; Jianli YANG ; Keqing LI ; Luxian LV ; Qingrong TAN ; Yinfei LI ; Hua YU ; Hongyan ZHANG ; Xin MA ; Fude YANG ; Lingjiang LI ; Chuanyue WANG ; Huiyao WANG ; Xiaojing LI ; Wanjun GUO ; Xun HU ; Yang TIAN ; Xiaohong MA ; Jeremy COID ; Dai ZHANG ; Chao CHEN ; Tao LI ; Chinese Antipsychotics Pharmacogenomics Consortium
Neuroscience Bulletin 2019;35(6):1102-1105
9.Abnormal Brain Structure and Function in First-Episode Childhood- and Adolescence-Onset Schizophrenia: Association with Clinical Symptoms.
Yanhong XIA ; Dan LV ; Yinghui LIANG ; Haisan ZHANG ; Keyang PEI ; Rongrong SHAO ; Yali LI ; Yan ZHANG ; Yuling LI ; Jinghua GUO ; Luxian LV ; Suqin GUO
Neuroscience Bulletin 2019;35(3):522-526
10.Investigation of orbitofrontal sulcogyral pattern in children and adolescents with schizophrenia
Haisan ZHANG ; Yan LI ; Yun LI ; Kun LI ; Bi WANG ; Suqin GUO ; Luxian LYU ; Hongxing ZHANG
Chinese Journal of Nervous and Mental Diseases 2018;44(3):161-165
Objective To explore the association between the structural patterns of orbitofrontal sulcogyral pattern (OSP)and the susceptibility to schizophrenia in children and adolescents patients with schizophrenia. Methods Seventy-two childhood and adolescence schizophrenia aged 6~18 years were enrolled as the case group and 78 sex-, age-, education-matched healthy children served as the control group. MR images were acquired with a 3.0 T Magnetom Symphony MRI system. Positive and Negative Syndrome Scale (PANSS) was used to evaluate the symptom severity of patients.The pattern type of OFC was classified based on continuity among medial (MOS),lateral (LOS)and transverse (TOS) orbital sulci according to the method of Chiavaras and Petrides'. The orbitofrontal cortex (OFC) sulcogyral pattern was classified into three types(TypeⅠ,TypeⅡ,TypeⅢ)in each hemisphere. Results There were significant differences in the distribution of OFC patterns between the control and the case group (Left hemisphere: Χ2=6.668,P=0.036; Right hemisphere: Χ2=7.501,P=0.024). The linear regression analysis showed that Type Ⅲ in either hemisphere was associated with more severe symptoms in schizophrenia patients (B=7.214, P=0.008). Conclusions Type Ⅲ sulcogyral pattern may be a morphological risk marker for schizophrenia. Compared to the other two types, the Type Ⅲ expression is associated with more severe clinical symptoms.

Result Analysis
Print
Save
E-mail