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

Background: Diagnosis of schizophrenia lacks of reliable medical diagnostic tests and robust biomarkers applied to clinical practice. Schizophrenic patients undergoing treatment with SGAs suffer a reduced life expectancy due to metabolic disarrangements that co-exist with their own mental illness and predispose them to develop metabolic syndrome, also exacerbated by antipsychotic treatment. 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 the schizophrenia scene (e.g., uric acid); 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 the metabolic side-effects associated to its antipsychotic-treatment, represent an urgent request for scientifics and clinicians. Considering the biological environment that covers mental illness is a challenge needy of cutting-edge technologies such as metabolomics to strengthen solid biomarkers and preventive, diagnostic and therapeutical solutions.pre-print232 K