Study On The Correlation Between FOXO Pathway Related Gene Expression Level And The Onset,Clinical Symptoms And Clinical Efficacy Of Schizophrenia

Objective:To investigate the mRNA expression levels of FOXO pathway-related genes in peripheral blood of patients with acute schizophrenia before and after treatment with antipsychotic drugs,and to explore its role in the pathogenesis of schizophrenia and the effect of antipsychotie drugs on it.Methods:Forty-five patients who met the diagnostic criteria for acute schizophrenia in the American Diagnostic and Statistical Manual of Mental Disorders(DSM-?)were selected as the experimental group by random number table method.Forty-six patients from the health checkups in our hospital were selected as the normal control group.Patients enrolled in the unmedicated schizophrenia were treated with a new antipsychotic drug(olanzapine 5 mg-20 mg every day,average therapeutic dose 14.24±4.35)for 4 weeks,and the therapeutic amount was added within one week,and then the drug dose was kept stable.The PANSS scale was used to assess the patient's psychotic symptoms on the day of enrollment and 4 weeks after drug treatment.All subjects received venous blood on an empty stomach at 6 am,and total RNA extraction from whole blood must be completed within 3 hours,and directly subjected to reverse transcription and frozen at-80?.After the completion of all specimen collection,the expression levels of FOXO3,FOXO1,BCL2L11 and FASLG genes were quantitatively detected by two-step method and qPCR fluorescence.Data compilation and analysis were performed using SPSS 19.0 statistical software package.Results:A total of 45 patients with acute schizophrenia who met the inclusion criteria were enrolled in the study.Of these,33 were followed up,12 were shedding,and 46 were healthy controls.There were no significant differences in demographic data and male-female ratio between the two groups at baseline(P>0.05).1.Kolmogorov-Smirnov test showed that the expression level data of four target genes did not conform to normal distribution.Levene variance homogeneity test showed that the expression level data of four target genes were not uniform.Kruskal Wallis nonparametric test was used to compare the expression level of target genes between the study group and the control group before and after treatment.There were significant differences in the mRNA expression levels of FOXo1(?2=70.531,P=0.000),FOXO3A(?2=86.130,P=0.000),FASLG(?2=51.294,P=0.000),BCL2L11(?2=41.201,P=0.000)between three groups of samples.The Tamhane test was chosen for comparison between 2 groups.The results showed that FOXO1(MDc=2.765,P=0.000),FOXO3A(MDc=2.720,P=0.000),FASLG(MDc=1.330,P=0.000),BCL2L11(MDc=1.431,P=0.000)gene mRNA expression levels were significantly down-regulated in the acute schizophrenic patients before treatment compared with the normal control.Compared with the patients before treatment,the expression levels of FOXO1(MDa=0.573,P=0.000),FOXO3A(MDa=0.664,P=0.000),FASLG(MDa=0.467,P=0.000)were significantly down-regulated in schizophrenic patients after treatment,the difference was statistically significant,BCL2L11(MDa=0.690,P=0.928)was not statistically significant;After treatment,the gene mRNA expression levels of FOXO1 FOXO1(MDb=3.339,P=0.000),FOXO3A(MDb=M.384,p=0.000),FASLG(MDb=1.798,P=0.000),BCL2L11(MDb=1.500,P=0.000)were significantly down-regulated in schizophrenic patients compared with the normal control.2.In the patients with acute schizophrenia before treatment,the gene expression levels of FOXO1 was positively correlated with FOXO3A(r=0.602,P<0.05)and BCL2L11(r=0.584,P<0.05),FOXO3A gene expression level was positively correlated with FASLG(r=0.417,P<0.05)and BCL2L11(r=0.996,P<0.05),and FASLG gene expression level was positively correlated with BCL2L11(r=0.440,P<0.05),the correlation between FOXO1 gene expression level and FASLG(r=0.064,P>0.05)gene expression level did not reach a significant level.In the patients with acute schizophrenia after treatment,there was a significant positive correlation between FOXO1 gene expression level and FOXO3A(r=0.653,P<0.05),BCL2L11(r=0.654,P<0.05),FOXO3A gene expression level and BCL2L11(r=1.000,P<0.05),FASLG gene expression level and FOXO1(r=0.140,P>0.05),no significant correlation between FASLG gene expression and FOXO1(r=0.140,P>0.05),FOXO3A(r=0.134,P>0.05),BCL2L11(r=0.137,P>0.05).In the normal control,the expression level of FOXO1 gene was positively correlated with FOXO3A(r=0.54 7,P<0.05),FASLG(r=0.783,P<0.05)and BCL2L11(r=0.552,P<0.05).FOXO3A gene expression level was positively correlated with FASLG(r=0.514,P<0.05)and BCL2L11(r=0.999,P<0.05).The level of FASLG gene expression was positively correlated with BCL2L11(r=0.523,P<0.05)gene expression level.3.The post-treatment group of patients with acute schizophrenia showed that FASLG expression levels were associated with disease duration(r=0.367,P=0.039).The other 3 groups of 4 target genes were not associated with age,gender,marital status,first recurrence,first onset age,duration of disease,education level,total and factor scores of PANSS(P>0.05).Conclusion:1.Down-regulation of FOXO pathway-related gene expression is involved in the pathogenesis of schizophrenia.2.Antipsychotic treatment can alter the expression level of FOXO pathway-related genes in patients with acute schizophrenia.3.There are synergistic interactions between FOXO pathway related genes.4.The expression level of FOXO pathway related genes is possibly related to the course of schizophrenia.