Study Of Energy Metabolic And Immune Dysfunctions In Schizophrenia

Schizophrenia is a common mental disturbance with a global prevalence of about 0.5～1 %,characterized by low cure rate and high recurrence rate.The severe symptoms of schizophrenia including psychosis,apathy and social withdrawal,and cognitive impairment.The increasing prevalence of schizophrenia makes it become a serious public health problem and social economic burden.However,instead of centennial basic researches and clinical explorations,schizophrenia is still mysterious.Systematic studies combined with bioinformatics analysis are essential to explore the pathogenesis of schizophrenia.High-throughput genetic researches have provided reliable directions for etiological researches of schizophrenia including metabolism and immunity.Due to the close connections between periphery and CNS,blood samples,which are controllable in recruiting patients with different stages and medications,are superior for schizophrenia study.Proteomic techniques can be used as a non-biased screening approach and provided insights into the pathways affected in the disease.In this dissertation,we aimed to uncover the roles of energy metabolism and immunity in the pathogenesis of schizophrenia by a proteomic based systematic study in leukocyte and relevant metabolites and cf DNA detections in plasma.A total of 3152 proteins were identified using UPLC-MS/MS,in which475 were differentially expressed.GO enrichment and KEGG pathway analyses revealed that metabolism,immunity,and cell redox state were significantly altered.Deeper analysis revealved that many proteins involved in glycolysis,TCA cycle,and oxidative phosphorylation were increased,suggesting an upregulated energy metabolism in schizophrenia patients.In complement activation pathway,upstream complement component and related regulatory proteins were significantly increased while complement molecule C8 which involved in membrane attack complex formation was significantly decreased,indicating impaired complement activation in schizophrenia.Numerous proteins involved in antioxidant and apoptosis also changed,which implied an increased oxidative stress and apoptosis in schizophrenia.Moreover,increased pyruvate level,lactate level,and dereased lactate-to-pyruvate ratio were observed in patients with schizophrenia.Significantly increased cf DNA levels and shortened cf DNA fragments which might be induced by apoptosis were also found in patients.These results further support the findings in proteomic study and provide candidate biomarkers for the clinical diagnoses of schizophrenia.This study systematically revealed the role of energy metabolism and complement system in the pathogenesis of schizophrenia,and further proposed that apoptosis was activated in schizophrenia.The findings could provide new evidences and direction for future schizophrenia research.