Metabolomic Connections between Schizophrenia, Antipsychotic Drugs and Metabolic Syndrome: A Variety of Players

Abstract

Background: Diagnosis of schizophrenia lacks reliable medical diagnostic tests and robust biomarkers applied to clinical practice. Schizophrenic patients undergoing treatment with antipsychotics suffer reduced life expectancy due to metabolic disarrangements that co-exist with their mental illness and predispose them to develop metabolic syndrome, which is also exacerbated by medication. Metabolomics is an emerging and potent technology able to accelerate this biomedical research. Aim: This review focus on a detailed vision of the molecular mechanisms involved both in schizophrenia and antipsychotic-induced metabolic syndrome, based on innovative metabolites that consistently change in nascent metabolic syndrome, drug-naïve, first episode psychosis and/or schizophrenic patients compared to healthy subjects. Main Lines: Supported by metabolomic approaches, although not exclusively, noteworthy variations are reported mainly through serum samples of patients and controls in several scenes: 1) alterations in fatty acids, inflammatory response indicators, amino acids and biogenic amines, biometals, and gut microbiota metabolites (schizophrenia); 2) alterations in metabolites involved in carbohydrate and gut microbiota metabolism, inflammation and oxidative stress (metabolic syndrome), some of them shared with schizophrenia; 3) alterations of cytokines secreted by adipose tissue, phosphatidylcholines, acylcarnitines, Sirtuin 1, orexin-A, and changes in microbiota composition (antipsychotic-induced metabolic syndrome). Conclusion: Novel insights into the pathogenesis of schizophrenia and metabolic side-effects associated with its antipsychotic treatment represent an urgent request for scientists and clinicians. Leptin, carnitines, adiponectin, insulin, or interleukin-6 represent some examples of candidate biomarkers. Cutting-edge technologies like metabolomics have the power to strengthen research for achieving preventive, diagnostic, and therapeutical solutions for schizophrenia.