Alteration mRNA Expression Profile of Autophagy Related mTOR Pathway in Schizophrenic Patients with Olanzapine Treatment.

Abstract Background: mTOR signaling pathway involves in the pathogenesis of schizophrenia and the mechanism of extrapyramidal adverse reactions of antipsychotic drugs, which might mediate by mTOR-dependent autophagy impairment. This study aimed to examine the mRNA expression levels of Mammalian rapamycin target protein (mTOR) pathway genes in schizophrenia patients with olanzapine treatment, which is considered to be an mTOR inhibitor and autophagy inducer. Methods: Thirty-two acute schizophrenia patients had been treated with olanzapine for four weeks (average dose 14.24 ± 4.35 mg/d), along with 32 healthy volunteers. Before and after olanzapine treatment, the Positive and Negative Syndrome Scale (PANSS) was used to evaluate the symptoms of schizophrenia patients, and the mRNA expression levels of mTOR pathway-related genes, including MTOR, RICTOR, RPTOR, and DEPTOR, were detected by real-time quantitative PCR with the fasting venous blood of all the samples. Results: The MTOR and RICTOR mRNA expression levels of acute schizophrenia patients significantly decreased than them of healthy controls, and furtherly significantly decreased after four weeks of olanzapine treatment. While DEPTOR mRNA expression levels of acute schizophrenia patients had no significant difference with them of healthy controls, but significantly increased after treatment. And the mRNA expression levels of RPTOR had no significant difference in the three groups. The pairwise correlation of MTOR, DEPTOR, RPTOR, and RICTOR mRNA expression levels in acute schizophrenia patients and healthy controls showed significant correlationships. After olanzapine treatment, the correlationships of mRNA expression levels disappeared between DEPTOR and MTOR, and also between DEPTOR and RICTOR. Conclusions: The results inferred the abnormalities of mTOR pathway, especially DEPTOR, might play important roles in autophagy mechanism of the pathophysiology in schizophrenia and olanzapine treatment.