1.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.
		                        		
		                        		
		                        		
		                        	
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.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.
		                        		
		                        		
		                        		
		                        	
4.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.
		                        		
		                        		
		                        		
		                        	
5.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.
		                        		
		                        		
		                        		
		                        	
6.Resting-state functional magnetic resonance imaging of supramarginal gyrus-cerebellum circuit in obsessive-compulsive disorder
Qingjiang ZHAO ; Haisan ZHANG ; Bi WANG ; Nan YAO ; Yongfeng YANG ; Luxian LYU ; Hongxing ZHANG ; Xiaoyue WANG
Chinese Journal of Behavioral Medicine and Brain Science 2019;28(2):127-132
		                        		
		                        			
		                        			Objective Regional homogeneity (ReHo) and functional connectivity (FC) were used to study obsessive-compulsive disorder(OCD),and to explore the mechanism of OCD in resting state.Method Resting-state functional magnetic resonance imaging (RS-fMRI) was performed in 55 patients with OCD (OCD group) and 50 normal controls (control group) matched by sex,age,nationality and education.The data and screening abnormal brain areas were analyzed and compared by DPARSFA2.3 and Rest software in OCD group.Whole brain FC analysis was performed with abnormal brain areas as seed points.Result Compared with the control group,ReHo in right thalamus (MNI:x=9,y=-24,z=6,t=4.3217) and left superior marginal gyrus (MNI:x =-45,y =-30,z =27,t =3.6320) increased and ReHo in right caudate nucleus (MNI:x=3,y=15,z=9,t=-3.1687) decreased in obsessive-compulsive disorder group,and the difference was statistically significant(P<0.05).Using left superior marginal gyrus,fight thalamus and right caudate nucleus as seed voxels,the whole brain FC analysis showed that there were abnormal functional connections between bilateral cerebellar foot 1/2 area and left supramarginal gyrus,right thalamus and right caudate nucleus (P<0.05) and the left supramarginal gyrus-bilateral cerebellum feet 1 area-right thalamic circuit and left supramarginal gyrus-bilateral cerebellum feet 1,2-right caudate nucleus-right thalamic circuit existed in 0CD group.Conclusion The left supramarginal gyrus-bilateral cerebellum feet 1 area-right thalamic circuit and left supramarginal gyrus-bilateral cerebellum feet 1,2-right caudate nucleus-right thalamic circuit may play an important role in the mechanism of OCD.
		                        		
		                        		
		                        		
		                        	
7.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.
		                        		
		                        		
		                        		
		                        	
8.Clinical Observation of 4 Kinds of the Second-generation Antipsychotic Drugs in the Treatment of Acute Phase of Schizophrenia
Jingyuan ZHAO ; Guangbiao HUANG ; Xiaojing GU ; Xiaoqing AI ; Shuzhen YANG ; Tingting HUA ; Luxian LYU
China Pharmacy 2016;27(20):2790-2794
		                        		
		                        			
		                        			OBJECTIVE:To investigate clinical efficacy and adverse reactions(ADRs)of 4 kinds of the second-generation anti-psychotic drugs in the treatment of acute phase of schizophrenia. METHODS:159 patients with schizophrenia were randomly divid-ed into risperidone group(40 cases),olanzapine group(40 cases),aripiprazole group(39 cases)and ziprasidone group(40 cas-es). All groups were given routine dosage of relevant medicine by routine usage for 6 weeks. Mental status of patients were mea-sured by PANSS before treatment and after 2,4 and 6 weeks of treatment. At the same time,blood glucose,blood lipid,prolac-tion and other metabolic and biological indicators were all detected. RSESE,BARS and UKU were adopted to evaluate ADR. RE-SULTS:A total of 100 patients completed the study. Compared with aripiprazole group and ziprasidone group,risperidone and olan-zapine inhibited symptom more rapidly,with statistical significance (P<0.05). After treatment,body mass index and abdominal circumference of olanzapine group were significantly higher than those of other 3 groups,with statistical significance (P<0.05). Low density lipoprotein of olanzapine group was increased significantly,there was statistical significance compared to ziprasidone group and aripiprazole group(P<0.05). Prolactin level of risperidone group was significantly higher than those of other 3 groups, while that of aripiprazole group was significantly lower than those of other 3 groups,with statistical significance(P<0.05). ADRs of 4 drugs were mild or moderate,most of whom could be alleviated by symptomatic treatment. CONCLUSIONS:In the treatment of acute phase schizophrenia,4 drugs of the second-generation have similar curative effect in symptoms control,among which ris-peridone and olanzapine inhibit positive symptom more rapidly while more ADRs that related to lipid and glucose metabolism and prolactin also show. Aripiprazole and ziprasidone induce less ADRs relatively,and patients show better tolerability. Physicians should consider all kinds of factors in drugs selection,and make individualized treatment plan.
		                        		
		                        		
		                        		
		                        	
9.The effect of amisulpride on prolactin level and clinical efficacy in first-episode schizophrenic patients
Chinese Journal of Behavioral Medicine and Brain Science 2015;24(1):38-41
		                        		
		                        			
		                        			Objective To discuss the effect of amisulpride on the prolactin level in serum of first-episode schizophrenic patients and its relationship with symptoms.Methods 45 patients who met the DSM-IV schizophrenia diagnostic criteria and 45 age-and gender-matched healthy controls were assessed the clinical symptoms using positive and negative syndrome scale(PANSS) and pmlactin level in serum was detected using enzymelinked immunosorbent assay.Student's t test was used to compare the prolactin level before and after amisulpride treatment and correlation analysis was used to investigate the relationship between prolactin level in serum and symptoms with P<0.05 were considered significantly different.Results There was significant increase in prolactin level in serum after amisulpride treatment in first-episode schizophrenic patients((12.52±8.85) ng/ml,(52.60±22.93 ng/ml,t=12.165,P<0.001).There was a positive correlation between prolactin level in serum and reduction rate of negative symptoms (r=0.24,P<0.05).Conclusion Amisulpride can increase prolactin level in serum;and the rise of serum prolactin is closely related to the improvement of negative symptoms.
		                        		
		                        		
		                        		
		                        	
10.Changes of glial cells and white matter in pubescent stage of schizophrenia rats
Shuang DING ; Yanli LU ; Fancui MENG ; Jin ZHAO ; Wenqiang LI ; Luxian LYU
Chinese Journal of Behavioral Medicine and Brain Science 2015;24(10):873-876
		                        		
		                        			
		                        			Objective To explore the changes of pubescent immune response in the schizophrenia offspring induced by poly(I:C) during pregnancy and the effects on white matter.Methods The obtained pregnant rats were randomly divided into model group(n=6) and control group (n=5), receiving either poly (I:C) at a dose of 10 mg/kg diluted in 0.9% NaC1 solution or vehicle solution alone (sterile pyrogen-free 0.9% NaC1) on gestation day 9 (GD9).Immunohistochemical technique(IHC) was applied to detect the changes of microglias and astrocytes in the prefrontal cortex(PFC) and hippocampus(HC) of partly offsprings in the two groups at the sixth week,as well as Luxol fast blue(LFB) for the changes of white matter.The other offsprings of each group were selected for behavioral assessment at the eighth week.Results The results of prepulse inhibition test showed that PP2, PP4 and PP8 of model groups were significantly lower than that of the control group at young adult(P<0.01).In passive avoidance test, and the T1 results of model group were significantly higher than those of the control group, the T results of model group were lower than those of control group (P< 0.01).Immunohistochemical results indicated that the number of microglias in the model group((264±33)/mm2, (271 ±38)/mm2) was significantly increased in PFC and HC than that in the control group((140±29)/mm2, (169±37)/mm2, P<0.05) ,which was accompanied with significant morphological changes, while the OD value of astrocyte protein expression in the frontal lobe and hippocampus had no obvious difference between the model group and control group(P>0.05).The OD value of LFB staining for myelin in the model group(0.29±0.02) was significantly decreased compared with that in the control group(0.33±0.03)(P<0.01).Conclusion The young adult offsprings with prenatal infection present obvious schizophrenia-like behavior, meanwhile, the microglias activation and demyelination changes in white matter are observed,which provides more evidence for the relationship between immune response and white matter in the pathogenesis of schizophrenia.
		                        		
		                        		
		                        		
		                        	
            
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