Metabolic Biomarkers In Patients With Bipolar Depression Based On ~1H NMR Metabolomics

Objective:1.Find differential metabolites and related metabolic pathways in plasma and urine of patients with bipolar depression;2.Analysis of differential metabolites and involvement of metabolic pathways to explore possible etiology and pathogenesis of bipolar depression.Methods:Thirty-seven patients with bipolar depression and 48 normal controls were recruited according to the DSM-V diagnostic criteria.General demographic data,clinical symptom data,and blood and urine biological samples were collected.The samples were centrifuged at 3000 r/min for 15 minutes and stored at-80�C refrigerator.After thawing the plasma and urine samples,they were separated by the compounds and then measured on a Bruker 600MHz AVANCE III NMR spectrometer to obtain typical ~1H NMR spectra.Material identification was performed on the maps,and Fourier transform,phase and baseline adjustments were performed on the maps using the MestReNova software.The integration data was imported into SIMCA-P 14.1 software for PLS-DA and OPLS-DA analysis,resulting in an OPLS-DA score plot.In order to find differential metabolites,a corresponding load map was established based on the score map.Differential metabolites were analyzed by ANOVA in SPSS 16.0 software to meet VIP>1 and P<0.05 as differential metabolites.To determine the relevant pathways for differential metabolites,MetPA was further introduced for metabolic pathway analysis.Results:1.General information:There was no statistically significant difference in gender and age between the bipolar depression group and the normal control group,and there were significant depression and anxiety symptoms in the bipolar depression group.2.Results of plasma samples:There are seven differential metabolites in plasma:lactate,trimethylamine oxide,N-acetyl glycoprotein,choline,?-glucose,glycine,and?-glucose,which can effectively distinguish between the patient group and the control group.The group,involved metabolic pathways are glycolysis or gluconeogenesis,methane metabolism,galactose metabolism,glycerophospholipid metabolism,glycine,serine and threonine metabolism,starch and sucrose metabolism,pyruvate metabolism;3.Urine sample results:There are 7 different metabolites in the urine:betaine,glycerine,hippuric acid,inosine sulfate,trimethylamine oxide,urea,inositol,which can effectively distinguish between the patient group and the control group.The metabolic pathways involved are galactose metabolism,vitamin C metabolism,pyrimidine metabolism,glycine,serine and threonine metabolism,phenylalanine metabolism,arginine and valine metabolism,glycerol lipid metabolism,inositol phosphate metabolism,purine metabolism.Conclusion:In this study,seven metabolites such as lactic acid,trimethylamine oxide,N-acetyl glycoprotein,choline,?-glucose,glycine,and?-glucose were found in plasma through ~1H NMR metabolomics methods,involving seven metabolic pathways.Seven metabolites of betaine,glycerol,hippuric acid,indoxyl sulfate,inositol,trimethylamine oxide,and urea were found in the urine,involving 9 metabolic pathways:1.Glycolysisandgluconeogenesis,galactosemetabolism,starchandsucrose metabolism and pyruvate metabolism is related to energy metabolism;2.Glycerol phospholipid metabolism is related to lipid metabolism;3.Phenylalanine metabolism,glycine,serine and threonine metabolism,arginine and valine metabolism is related to amino acid metabolism;4.Purine pyrimidine metabolism,vitamin metabolism,inositol phosphate metabolism and methane metabolism is related to other metabolism.It is suggested that patients with bipolar depression have metabolic abnormalities such as energy,lipids,and amino acids,providing research ideas for the etiology and pathogenesis of the disease.