title: Metabolomic profiling of schizophrenia patients at risk for metabolic syndrome.
abstract: Second-generation antipsychotics (SGAs) are commonly used to treat schizophrenia. However, SGAs cause metabolic disturbances that can manifest as metabolic syndrome (MetS) in a subset of patients. The causes for these metabolic disturbances remain unclear. We performed a comprehensive metabolomic profiling of 60 schizophrenia patients undergoing treatment with SGAs that puts them at high (clozapine, olanzapine), medium (quetiapine, risperidone), or low (ziprasidone, aripiprazole) risk for developing MetS, compared to a cohort of 20 healthy controls. Multiplex immunoassays were used to measure 13 metabolic hormones and adipokines in plasma. Mass spectrometry was used to determine levels of lipids and polar metabolites in 29 patients and 10 controls. We found that levels of insulin and tumor necrosis factor alpha (TNF-α) were significantly higher (p < 0.005) in patients at medium and high risk for MetS, compared to controls. These molecules are known to be increased in individuals with high body fat content and obesity. On the other hand, adiponectin, a molecule responsible for control of food intake and body weight, was significantly decreased in patients at medium and high risk for MetS (p < 0.005). Further, levels of dyacylglycerides (DG), tryacylglycerides (TG) and cholestenone were increased, whereas α-Ketoglutarate and malate, important mediators of the tricarboxylic acid (TCA) cycle, were significantly decreased in patients compared to controls. Our studies suggest that high- and medium-risk SGAs are associated with disruption of energy metabolism pathways. These findings may shed light on the molecular underpinnings of antipsychotic-induced MetS and aid in design of novel therapeutic approaches to reduce the side effects associated with these drugs.
authors.affiliation: Department of Psychiatry,University of Texas Health Science Center San Antonio,San Antonio, TX,USA.
authors.forename: R Madelaine
authors.initials: RM
authors.lastname: Paredes
authors.affiliation: Department of Psychiatry,University of Texas Health Science Center San Antonio,San Antonio, TX,USA.
authors.forename: Marlon
authors.initials: M
authors.lastname: Quinones
authors.affiliation: Department of Cellular and Structural Biology,University of Texas Health Science Center San Antonio,San Antonio, TX,USA.
authors.forename: Ketan
authors.initials: K
authors.lastname: Marballi
authors.affiliation: Department of Biochemistry,University of Texas Health Science Center San Antonio,San Antonio, TX,USA.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Gao
authors.affiliation: Department of Psychiatry,University of Texas Health Science Center San Antonio,San Antonio, TX,USA.
authors.forename: Celina
authors.initials: C
authors.lastname: Valdez
authors.affiliation: Department of Medicine,University of Texas Health Science Center San Antonio,San Antonio, TX,USA.
authors.forename: Seema S
authors.initials: SS
authors.lastname: Ahuja
authors.affiliation: Department of Psychiatry,University of Texas Health Science Center San Antonio,San Antonio, TX,USA.
authors.forename: Dawn
authors.initials: D
authors.lastname: Velligan
authors.affiliation: Department of Psychiatry,University of Texas Health Science Center San Antonio,San Antonio, TX,USA.
authors.forename: Consuelo
authors.initials: C
authors.lastname: Walss-Bass
mesh_terms: D052242:Adiponectin / Q000097:blood; D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects*; D016022:Case-Control Studies; D002783:Cholestenones / Q000097:blood; D004075:Diglycerides / Q000097:blood; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood; D007656:Ketoglutaric Acids / Q000097:blood; D008293:Malates / Q000097:blood; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000150:complications / Q000378:metabolism*; D055432:Metabolomics; D012559:Schizophrenia / Q000097:blood / Q000150:complications / Q000188:drug therapy / Q000378:metabolism*; D014280:Triglycerides / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D055815:Young Adult
chemical_list: D052242:Adiponectin; D014150:Antipsychotic Agents; D002783:Cholestenones; D004075:Diglycerides; D007328:Insulin; D007656:Ketoglutaric Acids; D008293:Malates; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; C030298:malic acid