Metabolomic profiling of schizophrenia patients at risk for metabolic syndrome
| Autor: | Celina Valdez, Marlon P. Quinones, Seema S. Ahuja, Consuelo Walss-Bass, R. Madelaine Paredes, Ketan K. Marballi, Xiaoli Gao, Dawn I. Velligan |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Olanzapine
Adult Male medicine.medical_specialty medicine.drug_class Malates Atypical antipsychotic Diglycerides Young Adult Internal medicine Medicine Humans Insulin Metabolomics Pharmacology (medical) Ziprasidone Clozapine Cholestenones Triglycerides Pharmacology Metabolic Syndrome Adiponectin business.industry Tumor Necrosis Factor-alpha medicine.disease Psychiatry and Mental health Endocrinology Case-Control Studies Schizophrenia Quetiapine Ketoglutaric Acids Aripiprazole Female Metabolic syndrome business medicine.drug Antipsychotic Agents |
| Zdroj: | The international journal of neuropsychopharmacology. 17(8) |
| ISSN: | 1469-5111 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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