Metabolomic profiling of schizophrenia patients at risk for metabolic syndrome

R. Madelaine Paredes, Marlon Quinones, Ketan Marballi, Xiaoli Gao, Celina Valdez, Seema S. Ahuja, Dawn Velligan, Consuelo Walss-Bass

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1139-1148
Number of pages10
JournalInternational Journal of Neuropsychopharmacology
Volume17
Issue number8
DOIs
StatePublished - Aug 20 2014

Keywords

  • Adipokines
  • metabolic syndrome
  • metabolomics
  • schizophrenia
  • second-generation antipsychotics

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)

Fingerprint Dive into the research topics of 'Metabolomic profiling of schizophrenia patients at risk for metabolic syndrome'. Together they form a unique fingerprint.

Cite this