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

Abstract

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-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; 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.

Exploring the Key Targets and Compounds That Manipulate Brain Neurocircuits Against Mental Disorders and Psychiatric

“…Prior studies have also found acylcarnitines levels with abnormalities in the plasma of patients with schizophrenia and familial Mediterranean fever (Kiykim et al, 2016;Cao et al, 2020). Moreover, the regulation of L-carnitine metabolites by antipsychotic drugs has been reported in clinical studies (Lheureux and Hantson, 2009;Molina et al, 2021;Yi et al, 2021), and in animal studies (Albaugh et al, 2012;, particularly in two early studies in patients with schizophrenia after treatment (Kriisa et al, 2017;Cao et al, 2019b). All these findings support our finding that the carnitine pathway can be regulated by OLA.…”

A Preliminary Comparison of Plasma Tryptophan Metabolites and Medium- and Long-Chain Fatty Acids in Adult Patients with Major Depressive Disorder and Schizophrenia

“…Because Trp and fatty acids metabolism is greatly affected by individuals, such as gender, age, eating habits, and smoking [ 7 , 68 ], the recruited cases are relatively small and the results still need a large sample to explore further. Meanwhile, considering that antidepressant and antipsychotic drugs could affect Trp and fatty acids metabolism [ 69 , 70 , 71 ], the influence of drugs on plasma Trp metabolites and the composition of fatty acids cannot be excluded. In addition, the detection methods based on mass spectrometry require expensive equipment and may lead to discrepancies in results.…”

Carnitine metabolites and cognitive improvement in patients with schizophrenia treated with olanzapine: a prospective longitudinal study

“…Prior studies have also found acylcarnitines levels with abnormalities in the plasma of patients with schizophrenia and familial Mediterranean fever ( Kiykim et al, 2016 ; Cao et al, 2020 ). Moreover, the regulation of L-carnitine metabolites by antipsychotic drugs has been reported in clinical studies ( Lheureux and Hantson, 2009 ; Molina et al, 2021 ; Yi et al, 2021 ), and in animal studies ( Albaugh et al, 2012 ; Jiang et al, 2019 ), particularly in two early studies in patients with schizophrenia after treatment ( Kriisa et al, 2017 ; Cao et al, 2019b ). All these findings support our finding that the carnitine pathway can be regulated by OLA.…”