Changes Of Metabonomics In Plasma From The Patients With Schizophrenia Before And After Treatment With Modified Electroconvulsive Therapy

BackgroundModified electroconvulsive therapy(MECT)is a definite physical treatment for schizophrenia(SCZ),but its mechanism is still unclear.It can be affirmed that there are something changes(increase or decrease)during the treatment.And this is helpful to the recovery of symptoms.Metabonomics is one of the feasible methods to detect the changes of metabolites after disturbance or stimulation.In this study,metabolomic techniques were used to study the changes of plasma metabolites in schizophrenic patients before and after MECT,which may provide clues to explore the therapeutic mechanism of ECT,and may also provide reference information for the study of the pathological mechanism of schizophrenia.ObjectivesTo understand the changes of plasma metabonomics in schizophrenic patients before and after MECT treatment and to obtain differential metabolites information.To provide information for exploring the therapeutic mechanism of MECT,and to provide reference for exploring the pathological mechanism of schizophrenia.Methods1.Seventy-two cases of schizophrenia met the diagnostic criteria of Diagnostic and Statistical Manual of Mental Disorders,Fourth Edition,DSM-IV,of which 38 were scheduled to receive modified electroconvulsive therapy(MECT group)and 34 were treated with antipsychotic drugs(Drug group).30 healthy controls(control group).The Drug group and the control group matched the MECT group in terms of age,sex,educational years,and drug use in the Drug group matched that in the MECT group..MECT group was included within 12 hours before MECT,followed up within 24 hours after the 8th MECT(about 19-20 days),and the Drug group was followed up from 19 to 20 days after admission.2.Positive and Negative Syndrome Scale(PANSS)was used to assess the severity of psychiatric symptoms in patients with schizophrenia at the time of enrollment and follow-up in MECT group and Drug group,and fasting plasma samples were collected in the morning for metabolomics test;fasting plasma samples were collected in the control group for metabolomics test.3.Using liquid chromatography-mass spectrometry(LC-MS)method to detect the metabolomics information of plasma,and using the metabolomics data processing software Progenesis QI v2.3 to analyze.Using SIMCA software package,differential metabolites were screened and enrichment analysis and KEGG pathway enrichment analysis were carried out.Results1.The total score of PANSS and each factor score of schizophrenia patients in MECT group and Drug group decreased significantly before and after treatment.The total score reduction rate of PANSS in MECT group was(44.54±12.12)%,and that in Drug group was(22.77±10.10)%.2.In MECT group,there were 13 differential metabolic pathways before and after treatment(P < 0.05): sphingolipid metabolic pathway,linoleic acid metabolic pathway,phenylalanine,tyrosine and tryptophan biosynthesis metabolic pathway,phenylalanine metabolic pathway,glycerophospholipid metabolic pathway,glycosylphosphatidylinositol anchored metabolic pathway,alpha-linolenic acid metabolic pathway,PPAR signaling pathway,neurotrophic factor signaling pathway,autophagy regulation pathway,melanogenesis pathway,gonadotropin releasing hormone signal transduction pathway,adipocytokine signal transduction pathway were managed,and 12 differential metabolitesincluding sphingosine,arachidonic acid,L-tyrosine,L-phenylalanine and phenylpyruvate were involved in the differential metabolic pathway(P < 0.05).3.There were 7 differential metabolic pathways in schizophrenia patients before and after treatment in the Drug group(< 0.05): glycerol phosphoric acid metabolic pathway,sphingolipid metabolic pathway,glycosylphosphatidylinositol anchored synthetic metabolic pathway,neurotrophic factor signal transduction pathway,autophagy regulation pathway,adipocytokine signal pathway,sulfur metabolic pathway,and there were 6different metabolites such as sulfate in the differential metabolic pathway(P < 0.05).4.Compared with the control group,there were 10 differential metabolic pathways in the MECT group and the Drug group(P < 0.05): primary bile acid metabolic pathway,glycerophospholipid metabolic pathway,unsaturated fatty acid metabolic pathway,sphingolipid metabolic pathway,linoleic acid metabolic pathway,glycosylphosphatidylinositol anchored metabolic pathway,linolenic acid metabolic pathway,autophagic regulation pathway,segmental pathway,gonadotropin releasing hormone signaling pathway,steroid synthesis and metabolism pathway,and there are 15 abnormal metabolites in different metabolic pathways,including 24 hydroxy-cholesterol,palmitic acid,arachidonic acid,alpha-linolenic acid,sphingosine,arachidonic acid(P <0.05).5.There were 7 differential metabolic pathways in schizophrenia patients before and after MECT treatment(P < 0.05): linoleic acid metabolic pathway,phenylalanine,tyrosine and tryptophan biosynthetic metabolic pathway,phenylalanine metabolic pathway,alpha-linolenic acid metabolic pathway,PPAR signaling pathway,melanogenesis pathway,gonadotropin releasing hormone signaling pathway in the differential metabolic pathway.There were 7 different metabolites,including arachidonic acid,L-tyrosine,L-phenylalanine and phenylpyruvic acid(P < 0.05).ConclusionsMECT can improve the psychiatric symptoms of schizophrenia,but also change the metabolic pathways of schizophrenia patients,including lipid metabolism,amino acid metabolism,neurotransmitter metabolism,immune function-related metabolism and endocrine function-related metabolism.