The Role Of MRNA Expression Level Of MTOR Pathway Related Genes In The Pathogenesis Of Schizophrenia

Objective:To study the changes of MTOR(mechanistic target of rapamycin kinase),DEPTOR(DEP domain containing MTOR interacting protein),RPTOR(regulatory associated protein of MTOR complex 1),RICTOR(RPTOR independent companion of MTOR complex2)gene expression levels before and after treatment in patients with acute schizophrenia,and to analyze their changes in schizophrenia.To explore the role of antipsychotic drugs in the pathogenesis of mTOR pathway-related genes.Methods:Forty-five schizophrenic patients in acute stage who were not taking medication were selected as case group according to DSM-Ⅳ(4th edition of American Mental Disorder Diagnosis and Statistics Manual).Forty-six healthy volunteers were selected as normal control group.The patients in the case group were treated with olanzapine,and the dosage of olanzapine was added to the dosage of olanzapine within a week(5-20 mg/d,the average dosage was 14.24+4.35 mg/d).The dosage of olanzapine remained unchanged after treatment.PANSS scale was used to assess the symptoms of patients during baseline period and four weekends of drug treatment.Fasting venous blood was collected at 6:30 a.m.and frozen at-80 C.After all samples were collected,the expression levels of MTOR,DEPTOR,RPTOR and RICTOR genes were quantitatively detected by qPCR fluorescence.The test data were analyzed by SPSS 19.0 software.Kruskal Wallis nonparametric test was used to compare the target gene expression level of the samples.P value less than 0.05 was defined as having statistical significance.Results:Forty-five patients with schizophrenia in acute phase were enrolled in this study.Among them,32 patients completed olanzapine treatment and follow-up for 4 weeks on time,and 13 patients dropped out.46 cases were enrolled into the control group.There was no significant difference in the ratio of male to female and demographic data between the case group and the control group(P>0.05).1.The comparison of target gene expression levels before and after treatment between the case group and the control group showed that the expression levels of MTOR(χ2=67.624,P<0.001),RPTOR(χ2=6.553,P=0.038),RICTOR(χ2=80.788,P<0.001)gene expression levels decreased significantly before and after treatment.The expression level of DEPTOR(Χ2=63.753,P<0.001)gene mRNA increased,and the difference was statistically significant.The results showed that MTOR(MD=1.556,P<0.001)gene expression level in the case group was lower than that in the control group before treatment,and there was no significant difference in DEPTOR(MD=0.971,P>0.05),RPTOR(MD=0.046,P>0.05),RICTOR(MD=2.476,P>0.05).The expression levels of MTOR(MD=0.568,P<0.001),RICTOR(MD=0.564,P=0.038)gene and DEPTOR(MD=3.506,P<0.001)gene were decreased,and the expression levels of DEPTOR(MD=0.702,P>0.05)gene were increased in the case group before and after treatment.There was no significant difference in the expression levels of RPTOR(MD=0.702,P>0.05).Compared with the control group,the expression levels of MTOR(MD=2.123,P<0.001),RPTOR(MD=0.748,P=0.038),RICTOR(MD=3.040,P<0.001)and DEPTOR(MD=4.477,P<0.001)decreased significantly after treatment,and the expression levels of DEPTOR(MD=4.477,P<0.001)increased significantly.2.The expression of MTOR gene was positively correlated with that of DEPTOR(r=0.771,P<0.05),RPTOR(r=0.430,P<0.05),RICTOR(r=0.987,P<0.05),and DEPTOR gene was positively correlated with that of RPTOR(r=0.441,P<0.05),RICTOR(r=0.754,P<0.05)before treatment.It was positively correlated with RICTOR(r=0.393,P<0.05)gene expression level.After treatment,MTOR gene expression level was positively correlated with RPTOR(r=0.482,P<0.05),RICTOR(r=1.000,P<0.05),DEPTOR gene expression level was positively correlated with RPTOR(r=0.435,P<0.05),and RPTOR gene expression level was positively correlated with RICTOR(r=0.483,P<0.05).There was no significant difference in the correlation between the expression level of MTOR(r=0.282,P>0.05)and RICTOR(r=0.281,P>0.05).In the control group,MTOR gene expression level was positively correlated with DEPTOR(r=0.622,P<0.05),RPTOR(r=0.60,P<0.05),RICTOR(r=0.997,P<0.05)gene expression level,DEPTOR gene expression level was positively correlated with RPTOR(r=0.476,P<0.05),RICTOR(r=0.626,P<0.05)gene expression level,and RPTOR gene expression level was positively correlated with RICTOR(r=0.601,P<0.05)gene expression level.The expression of NA was positively correlated.3.There was no correlation between the above four target genes before and after treatment in the case group and the normal control group and the PANSS score of age,gender,marital status,course of disease,educational level,first episode or recurrent course of disease.Conclusion:Findings of this study:(1).The mTOR pathway-related genes may be involved in the pathogenesis of schizophrenia.(2).The mTOR pathway related genes may play a synergistic role in the pathogenesis of schizophrenia and interact with each other.(3).Antipsychotic treatment can affect the mRNA expression level of genes related to the mTOR pathway,and DEPTOR gene may be one of the drug targets of olanzapine.(4).There was no correlation between mRNA expression level of mTOR pathway related genes and clinical features of schizophrenia.