Plasma Disturbance Of Phospholipid Metabolism In Major Depressive Disorder By Integration Of Proteomics And Metabolomics

Major depressive disorder(MDD)is a highly prevalent mental disorder with high morbidity and high mortality,affecting millions of human worldwide.It caused by a variety of factors that contribute to long-term depressing mood.A clear causative etiology of MDD remains unknown.In this study,we aim to identify critical protein alterations in plasma of MDD,and integrated our proteomics and previous metabolomics data to reveal significantly perturbed pathways in MDD.The iTRAQ based quantitative proteomics approach was conducted to compare plasma protein expression between depressed patients and healthy controls.For our integrative analysis,Ingenuity Pathway Analysis software was applied to analysis the proteomics and metabolomics data,and find the potential relationships among the differential proteins and metabolites.A total of 74 proteins were significantly changed in depressed patients compared with healthy controls.Bioinformatics analysis of differential proteins revealed significant alternation in lipid transport and metabolism function,including apolipoproteins(APOE,APOC4,APOA5)and serine protease inhibitor(SERPINA1).According to the canonical pathway analysis,the top 5 statistically significant pathways were related to lipid transport,inflammation and immunity.Causal network analysis by integrating the differential proteins and metabolites suggested that the disturbance of phospholipid metabolism might promote the inflammation in center nervous system(CNS).