The Level Of Gene Expression Of The DRD2-PI3k-AKT Signaling Pathway In The Pathogenesis Of Schizophrenia And Glycolipid Metabolism

Objective: to investigate the mRNA expression levels of both dopamine D2(DRD2)receptors and PI3K/AKT downstream signal transduction pathway in the white bloodcells (also spelled “leukocyte”) of peripheral blood for acute schizophrenia patients, toanalyze the relationship between the mRNA expression level, the symptoms ofpsychosis, and the sugar and lipid metabolism, and to investigate its benefit on thediagnosis and treatment of schizophrenia.Methods: From Jul.2011to Sep.2012, experimental studies were carried out on24acute phase schizophrenia inpatients,19long-term hospitalized patients and21normalcontrol subjects from Wuxi Mental Health Center. A real-time PR PCR method wasused for measuring the mRNA levels of DRD2and PI3K/AKT in the leukocytes ofperipheral blood. Relevant biochemical markers for sugar and lipid metabolism weremeasured as well. Furthermore, PANSS was used to assess the psychotic symptoms ofschizophrenia patients. Finally, we studied the relationship between the mRNA levels(DRD2and PI3K/AKT) in the leukocytes of peripheral blood, the psychotic symptoms,and the sugar and lipid metabolism for acute schizophrenia patients.Results:In the compare of the mRNA in the leukocytes of peripheral blood, the DRD2（F=102.73，P=0.00) and PI3K (F=2.30，P=0.11) are significant differently betweenthe acute stage with the normal control, while there is no difference between the chronicstage and the normal control. In AKT group, there is no diffference between the acutestage and the normal control, and there is significant difference between the chronic stage and the normal control（F=16.71，P=0.00). In glucose metabolism, the acute stagediffer from the normal control in fasting insulin（t=4.25，P=0.00）and insulin2hoursafter meal （t=3.10，P=0.01). And there is no difference in the aspects of fastingblood-glucose(FBG), glucose2hours after meal, fasting c-peptide, c-peptide2hoursafter meal. The HOMA-IR of acute patients has no relevant with PI3K, AKT, DRD2.And the HOMA-IR of acute patients compare with the HOMA-IR of the normal control,it’s a little high but still in the range of the normal value. Compare the lipid metabolismbetween the acute stage and the normal control, it can be found that total cholesterol（t=4.00，P=0.00）, HDL（t=7.77，P=0.00）, LDL （t=2.62，P=0.01）all significantlydifferent between the two groups, while triglyceride are similar in the two groups. ThePANSS scale scores are not relevant with the mRNA levels in the leukocytes ofperipheral blood.Conclusions:Compared with normal population, The PI3K/AKT and DRD2inperipheral blood are significantly different in these acute phase schizophrenia inpatients,but its amount of gene expression cannot find clear correlation with the clincalsymptoms. At the same time, schizophrenia patients have some problem in glycolipidmetabolism, suggesting that the DRD2-PI3K-AKT signaling pathway play an importantrole in the pathogenesis of schizophrenia and glycolipid metabolism.