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 antipsychotics suffer a reduced life expectancy due to metabolic disarrangements that co-exist with their mental illness and predispose them to develop metabolic syndrome, 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-naive, 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; 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 to its antipsychotic treatment, represent an urgent request for scientifics and clinicians. Leptin, carnitines, adiponectin, insulin or interleukin-6 represent some examples of candidate biomarkers. Cutting-edge technologies like metabolomics have the power of strengthen research for achieving preventive, diagnostic and therapeutical solutions for schizophrenia.