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.

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.

Objective:To investigate the efficacy, safety and possible mechanisms of celecoxib as an adjunctive treatment for schizophrenia.Methods:90 schizophrenic inpatients at the second affiliated hospital of Xinxiang Medical College from April 2019 to October 2020 were recruited and randomly assigned to a placebo group or the celecoxib adjunctive treatment group using a random number table. In the placebo group, 46 patients (29 males, 17 females; aged 21-34, mean age 27.46±6.50 years) completed a 6-week follow-up. In the celecoxib group, 44 patients (32 males, 12 females; aged 21-39, mean age 30.52±8.69 years) completed a 6-week follow-up. The Positive and Negative Syndrome Scale (PANSS) was used to assess psychiatric symptoms in both groups. Changes in PANSS score at the end of the treatment were compared to evaluate the efficacy of celecoxib. Metabolic indicators such as weight, body mass index, waist circumference and plasm glucolipid, as well as cardiovascular indicators like blood pressure, electrocardiogram and routine blood tests, and adverse events were collected for the safety evaluation. Serum tumor necrosis factor-α (TNF-α), Interleukin-4 (IL-4) and interferon-γ (IFN-γ) were also tested. Pearson correlation analysis was used to explore the relationship between cytokine levels, PANSS score, PANSS reduction rate [(pre-treatment score-post-treatment score)/pre-treatment score×100%], and the safety measurements in the two groups, analyzing the role of inflammation in celecoxib adjunctive therapy.Results:The change of PANSS positive score at the end of the 6th week was significantly higher in the celecoxib adjuvant treatment group than in the placebo group (-8.00±6.12 vs -4.78±5.19, H=-0.55, P=0.009). The weight changes, body mass index, total cholesterol, and triglycerides over 6 weeks were significantly lower in the celecoxib group compared to the placebo group ( F=-7.37, -7.30, 2.56, -2.54; all P<0.05). No serious adverse events were found in celecoxib adjuvant therapy. In the placebo group, baseline TNF-α levels were positively correlated with baseline negative symptoms and PANSS reduction rate ( r=0.260 and 0.330, both P<0.05), and negatively correlated with the 6-week weight ( r=-0.311, P<0.05); baseline IL-4 levels were positively correlated with the 6-week PANSS total score and the 6-week PANSS negative score ( r=0.320 and 0.397, both P<0.05), and negatively correlated with PANSS reduction rate and 6-week blood glucose ( r=-0.316 and -0.331, both P<0.05); Six-week IFN-γ levels were negatively correlated with low-density lipoprotein levels ( r=-0.306, P<0.05). And no such correlation was found in celecoxib adjuvant group. Conclusion:Celecoxib adjunctive therapy can improve positive symptoms of schizophrenia without causing adverse reactions. Inflammatory state is related to schizophrenia symptoms, treatment efficacy and metabolic abnormalities.

Objectives:To investigate the association between single nucleotide polymorphisms (SNP) of indoleamine 2,3-dioxygenase( IDO) genes and schizophrenia (SZ) in a Chinese Han population. Methods:Using a case-control study method, 3 700 in-patients with SZ were recruited from January 2010 to December 2021 at the Second Affiliated Hospital of Xinxiang Medical University, and 8 580 healthy controls were recruited from surrounding communities in Xinxiang City. The patient group and control group were matched in gender and age. After collecting peripheral blood from all subjects and extracting genomic DNA, the sample DNA was genotyped using methods such as gene chips and amplification refractory mutation system. The association analysis between IDO gene SNPs and SZ was conducted using the online analysis tool SHEsis. The differences in IDO gene SNP genotype and allele frequency between the two groups were compared using chi-square test. Linkage disequilibrium analysis, haplotype analysis, and Hardy Weinberg equilibrium test were performed using Haploview v4.2 software. A multifactor dimensionality reduction software was used to evaluate the interaction between SNPs and SNP frequencies. Results:In the four SNP loci of IDO gene, there was a significant difference in genotype and allele frequency between the SZ patient and the health control at rs9657182 locus (χ 2=11.81, P=0.003;χ 2=5.54, P=0.019). After Bonferroni correction, the genotype difference at rs9657182 locus still showed statistical significance ( P=0.011). There were no statistically significant differences in genotype and allele frequency among the three SNP locis (rs7820268, rs4503083, and rs10109853). Further stratified by gender, there was no significant difference in genotype frequency between the two groups at the rs9657182. Haplotype analysis revealed that the haplotype of CC and TC (rs9657182 and rs7820268) were significantly different between the two groups (χ 2=3.93,4.78, P=0.048, 0.029). Conclusion:The rs9657182 locus of IDO gene may be a susceptible locus for SZ. The haplotype of CC and TC may be associated with the onset of SZ.

Objective:To investigate the efficacy, safety and possible mechanisms of celecoxib as an adjunctive treatment for schizophrenia.Methods:90 schizophrenic inpatients at the second affiliated hospital of Xinxiang Medical College from April 2019 to October 2020 were recruited and randomly assigned to a placebo group or the celecoxib adjunctive treatment group using a random number table. In the placebo group, 46 patients (29 males, 17 females; aged 21-34, mean age 27.46±6.50 years) completed a 6-week follow-up. In the celecoxib group, 44 patients (32 males, 12 females; aged 21-39, mean age 30.52±8.69 years) completed a 6-week follow-up. The Positive and Negative Syndrome Scale (PANSS) was used to assess psychiatric symptoms in both groups. Changes in PANSS score at the end of the treatment were compared to evaluate the efficacy of celecoxib. Metabolic indicators such as weight, body mass index, waist circumference and plasm glucolipid, as well as cardiovascular indicators like blood pressure, electrocardiogram and routine blood tests, and adverse events were collected for the safety evaluation. Serum tumor necrosis factor-α (TNF-α), Interleukin-4 (IL-4) and interferon-γ (IFN-γ) were also tested. Pearson correlation analysis was used to explore the relationship between cytokine levels, PANSS score, PANSS reduction rate [(pre-treatment score-post-treatment score)/pre-treatment score×100%], and the safety measurements in the two groups, analyzing the role of inflammation in celecoxib adjunctive therapy.Results:The change of PANSS positive score at the end of the 6th week was significantly higher in the celecoxib adjuvant treatment group than in the placebo group (-8.00±6.12 vs -4.78±5.19, H=-0.55, P=0.009). The weight changes, body mass index, total cholesterol, and triglycerides over 6 weeks were significantly lower in the celecoxib group compared to the placebo group ( F=-7.37, -7.30, 2.56, -2.54; all P<0.05). No serious adverse events were found in celecoxib adjuvant therapy. In the placebo group, baseline TNF-α levels were positively correlated with baseline negative symptoms and PANSS reduction rate ( r=0.260 and 0.330, both P<0.05), and negatively correlated with the 6-week weight ( r=-0.311, P<0.05); baseline IL-4 levels were positively correlated with the 6-week PANSS total score and the 6-week PANSS negative score ( r=0.320 and 0.397, both P<0.05), and negatively correlated with PANSS reduction rate and 6-week blood glucose ( r=-0.316 and -0.331, both P<0.05); Six-week IFN-γ levels were negatively correlated with low-density lipoprotein levels ( r=-0.306, P<0.05). And no such correlation was found in celecoxib adjuvant group. Conclusion:Celecoxib adjunctive therapy can improve positive symptoms of schizophrenia without causing adverse reactions. Inflammatory state is related to schizophrenia symptoms, treatment efficacy and metabolic abnormalities.

Objectives:To investigate the association between single nucleotide polymorphisms (SNP) of indoleamine 2,3-dioxygenase( IDO) genes and schizophrenia (SZ) in a Chinese Han population. Methods:Using a case-control study method, 3 700 in-patients with SZ were recruited from January 2010 to December 2021 at the Second Affiliated Hospital of Xinxiang Medical University, and 8 580 healthy controls were recruited from surrounding communities in Xinxiang City. The patient group and control group were matched in gender and age. After collecting peripheral blood from all subjects and extracting genomic DNA, the sample DNA was genotyped using methods such as gene chips and amplification refractory mutation system. The association analysis between IDO gene SNPs and SZ was conducted using the online analysis tool SHEsis. The differences in IDO gene SNP genotype and allele frequency between the two groups were compared using chi-square test. Linkage disequilibrium analysis, haplotype analysis, and Hardy Weinberg equilibrium test were performed using Haploview v4.2 software. A multifactor dimensionality reduction software was used to evaluate the interaction between SNPs and SNP frequencies. Results:In the four SNP loci of IDO gene, there was a significant difference in genotype and allele frequency between the SZ patient and the health control at rs9657182 locus (χ 2=11.81, P=0.003;χ 2=5.54, P=0.019). After Bonferroni correction, the genotype difference at rs9657182 locus still showed statistical significance ( P=0.011). There were no statistically significant differences in genotype and allele frequency among the three SNP locis (rs7820268, rs4503083, and rs10109853). Further stratified by gender, there was no significant difference in genotype frequency between the two groups at the rs9657182. Haplotype analysis revealed that the haplotype of CC and TC (rs9657182 and rs7820268) were significantly different between the two groups (χ 2=3.93,4.78, P=0.048, 0.029). Conclusion:The rs9657182 locus of IDO gene may be a susceptible locus for SZ. The haplotype of CC and TC may be associated with the onset of SZ.

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.

Objective:This study evaluated the metabolic phenotype in offspring of maternal immune activation(MIA) rats, to determine whether it applies to the study of the mechanism of metabolic syndrome associated with schizophrenia, and to analyze its possible pathogenesis.Methods:Polyinosinic-polycytidylic acid (Poly I:C) or saline was injected via tail vein at 9.5 days of pregnancy, and the offspring were defined as MIA group and control group. Behavior, blood routine, blood glucose, blood lipid and liver function were detected. Besides, inflammatory cytokine levels were analyzed by quantitative PCR. The independent -sample t-test was used for the comparison between groups. Results:The results showed that the rats of the MIA group had an increased anxiety level, memory impairment, and sensory gating dysfunction in early adulthood. However, the rats of the MIA group already showed the risk of metabolic disorders in their adolescence, including the increased proportion of monocytes ( t=2.50, df=14, P=0.028), elevated LDL-C level ( t=3.34, df=14, P=0.005), and increased atherosclerosis index ( t=2.23, df=14, P=0.043). The rats of the MIA group showed abnormal liver morphology and decreased globulin ( t=3.61, df=14, P=0.003) and total protein levels ( t=3.40, df=14, P=0.004), suggesting possible impaired liver function. In addition, the rats of the MIA group showed systemic inflammation of the brain and liver. Conclusion:These results demonstrate that behavioral disorders and metabolic disorders coexist in the rats of the MIA group, and metabolic disorders appear earlier than significant behavioral abnormalities, suggesting the possible value of this model in the study of schizophrenia complicated by metabolic syndrome. In addition, systemic inflammation of the brain and liver may be a possible mechanism for behavioral disorders and metabolic disorders in the offspring of MIA.

Objective:This study evaluated the metabolic phenotype in offspring of maternal immune activation(MIA) rats, to determine whether it applies to the study of the mechanism of metabolic syndrome associated with schizophrenia, and to analyze its possible pathogenesis.Methods:Polyinosinic-polycytidylic acid (Poly I:C) or saline was injected via tail vein at 9.5 days of pregnancy, and the offspring were defined as MIA group and control group. Behavior, blood routine, blood glucose, blood lipid and liver function were detected. Besides, inflammatory cytokine levels were analyzed by quantitative PCR. The independent -sample t-test was used for the comparison between groups. Results:The results showed that the rats of the MIA group had an increased anxiety level, memory impairment, and sensory gating dysfunction in early adulthood. However, the rats of the MIA group already showed the risk of metabolic disorders in their adolescence, including the increased proportion of monocytes ( t=2.50, df=14, P=0.028), elevated LDL-C level ( t=3.34, df=14, P=0.005), and increased atherosclerosis index ( t=2.23, df=14, P=0.043). The rats of the MIA group showed abnormal liver morphology and decreased globulin ( t=3.61, df=14, P=0.003) and total protein levels ( t=3.40, df=14, P=0.004), suggesting possible impaired liver function. In addition, the rats of the MIA group showed systemic inflammation of the brain and liver. Conclusion:These results demonstrate that behavioral disorders and metabolic disorders coexist in the rats of the MIA group, and metabolic disorders appear earlier than significant behavioral abnormalities, suggesting the possible value of this model in the study of schizophrenia complicated by metabolic syndrome. In addition, systemic inflammation of the brain and liver may be a possible mechanism for behavioral disorders and metabolic disorders in the offspring of MIA.

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.