Study On Expression And Drug Efficacy Of MiR-195?BDNF And GABA-related Genes In Schizophrenia

Objective:Schizophrenia(SZ)is a serious mental health illness of unknown etiology,with characteristics of high prevalence,high morbidity and heavy social burden.The pathogenesis of schizophrenia has not yet been confirmed.And the complex genetic contribution and multifaceted epigenetic aspects still couldn't fully explain the etiopathogenesis of schizophrenia.The regulation of gene expression is considered to involed in the etiology of schizophrenia.The dysregulation of post-transcriptional regulation of miRNA is closely related to the development of neuropsychiatric disorder.Compared with normal people,the differences of miRNA expression profiles in brain tissues of schizophrenia patients were significantly different,which suggest that miRNA may be involved in the pathogenesis of schizophrenia.microRNA(miRNA),a newly discovered non-protein coding RNA,is one of the important members of the family.miRNA can participate in immune regulation,neuronal plasticity and mRNA transcription in the process of signal transduction in post-processing,which plays an important role in the central nervous system.miR-195 is a rich expression miRNA in the central nervous system.According to the literatures,miR-195 in the brain tissue and peripheral blood of patients with schizophrenia has different expression.miR-195 was reported to be related to BNDF(Brain-Derived Neurotrophic Factor)and GABA-related genes expression regulation,including Parvalbumin(PVALB)and Somatostatin(SST).This study investigates the role of miR-195 in the pathogenesis of schizophrenia,and aims to find out the correlation among the miR-195,NTRK2,BDNF,PVALB and SST gene expression.Furthermore,the correlation of gene expression and clinical outcome is also illuminated.Methods:1.SYBR Green real-time quantitative PCR technique were used to detect 121 patients with schizophrenia(including antipsychotics 8 weeks before and after treatment)and 142 normal controls in peripheral blood mononuclear cells of miR-195,BDNF,NTRK2,PVALB and SST gene mRNA expression levels.2.Patients with schizophrenia were followed up for 8 weeks.PANSS,SDSS and CGI were evaluated at the baseline and the end of 8 weeks.The cognitive functions of schizophrenia patients and normal controls were measured by RBANS.3.According to the results of Kolmogorov-Smirnov normality test,we choose independent sample t test or the Mann-Whitney U test to compare each gene mRNA expression level in the schizophrenia group and healthy controls.We choose the paired sample t test or paired sample Wilcoxon rank test to compare each gene mRNA expression level change in before and after treatment of schizophrenia patients.According to the characteristics of data,Spearman or Pearson correlation analysis was selected to study the correlation between mir-195,BDNF,NTRK2,PVALB and SST genes.4.According to the PANSS subtraction rate,the patients were divided into effective groups(the subtraction rate ?50%)and ineffective group(the subtraction rate < 50%).And the differences in gene expression between the two therapeutic groups and the normal control group were compared.According to the characteristics of data,Spearman or Pearson correlation analysis was selected to analyze the correlation between mRNA expression of each gene and the clinical characteristics of patients.Results:1.Compared with the normal control group,mRNA expression levels of NTRK2 and BDNF genes in the baseline period of schizophrenia were significantly increased,and the difference was statistically significant(P=0.000,P=0.004).The mRNA expression levels of mir-195,PVALB and SST genes were not statistically significant compared with those in the control group.2.In patients with schizophrenia,the expression level of mir-195 was negatively correlated with the expression level of PVALB(r=-0.397,P=0.000).The expression level of PVALB was positively correlated with NTRK2,BDNF and SST expression levels(r=0.437,P=0.000;r= 0.327,P = 0.003;r=0.343,P =0.343).The expression level of BDNF was positively correlated with NTRK2 and SST expression levels(r=0.338,P=0.002;r=0.539,P=0.000,and the expression level of SST was positively correlated with NTRK2 expression level(r=0.257,P=0.257).3.The patients with schizophrenia after eight weeks of antipsychotic medication,PANSS,SDSS and CGI rating scale decreased significantly(P all < 0.01),RBANS scale besides delay memory score was not a significant rise in attention,verbal,visual breadth,immediate memory and total score were significantly higher(P all < 0.01).Compared with the normal control group,the total score and factor scores of RBANS in schizophrenic patients decreased significantly,and the difference was statistically significant(P all < 0.01).4.The expression levels of mir-195,BDNF,NTRK2,SST and PVALB were not statistically significant before and after the use of the drugs for patients with schizophrenia(P all > 0.05).5.Compared with the invalid group of patients with schizophrenia,the mRNA expression level of mir-195 in the effective group increased,and the mRNA expression level of NTRK2 and PVALB decreased,the difference was statistically significant(P=0.015,P=0.002,P=0.016).Compared with the normal control group,the expression level of NTRK2 was significantly reduced,and the expression level of BDNF was significantly increased(P=0.016,P=0.007).6.The mRNA expression changes of mir-195 and NTRK2 were not correlated with the score changes of the scales.The change of mRNA expression of BDNF and PVALB was correlated with the score change of the PANSS scale and RBANS scale(r=-0.452,P=0.012;r= 0.409,P = 0.025;r=-0.420,P = 0.021;r=0.393,P=0.393).The change of mRNA expression in SST was only positively correlated with the delayed memory score in RBANS scale(r=0.418,P=0.022).Conclusions:1.miR-195 may not directly participate in the pathogenesis of schizophrenia,while BDNF and NTRK2 may participate in the occurrence of schizophrenia.2.Patients may have better efficacy of antipsychotic drugs with higher expression level of mir-195 and lower expression level of NTRK2 and PVALB.3.The expression level of mir-195 and NTRK2 was not related to antipsychotic drug therapy and cognitive function,and BDNF and PVALB were all related to drug therapy and cognitive function,while SST was only related to cognitive function.