A Marked Low-Grade Inflammation and a Significant Deterioration in Metabolic Status in First-Episode Schizophrenia: A Five-Year Follow-Up Study

The objective of this study was to evaluate how schizophrenia spectrum disorders and applied long-term (5.1 years) antipsychotic (AP) treatment affect the serum level of acylcarnitines (ACs), cytokines and metabolic biomarkers and to characterize the dynamics of inflammatory and metabolic changes in the early course of the disorder. A total of 112 adults participated in the study (54 patients with first-episode psychosis (FEP) and 58 control subjects). Biomolecule profiles were measured at the onset of first-episode psychosis and 0.6 years and 5.1 years after the initiation of APs. The results of the present study confirmed that specific metabolic–inflammatory imbalance characterizes AP-naïve patients. Short-term (0.6-years) AP treatment has a favourable effect on psychotic symptoms, as well as the recovery of metabolic flexibility and resolution of low-level inflammation. However, 5.1 years of AP treatment resulted in weight gain and increased serum levels of interleukin (IL)-2, IL-4, IL-6, IL-10, interferon-γ, hexoses, acetylcarnitine, short-chain ACs (C3, C4) and long-chain ACs (C16:2, C18:1, C18:2). In conclusion, despite the improvement in psychotic symptoms, 5.1 years of AP treatment was accompanied by a pronounced metabolic–inflammatory imbalance, which was confirmed by the presence of enhanced pro-inflammatory activity and increased obesity with changes in the metabolism of carbohydrates, lipids, and their metabolites

Metabolomics approach revealed robust changes in amino acid and biogenic amine signatures in patients with schizophrenia in the early course of the disease

Abstract The primary objective of this study was to evaluate how schizophrenia (SCH) spectrum disorders and applied antipsychotic (AP) treatment affect serum level of amino acids (AAs) and biogenic amines (BAs) in the early course of the disorder. We measured 21 different AAs and 10 BAs in a sample of antipsychotic (AP)-naïve first-episode psychosis (FEP) patients (n = 52) at baseline, after 0.6-year as well as after 5.1-year treatment compared to control subjects (CSs, n = 37). Serum levels of metabolites were determined with AbsoluteIDQ p180 kit using flow injection analysis tandem mass spectrometry and liquid chromatography technique. Elevated level of taurine and reduced level of proline and alpha-aminoadipic acid (alpha-AAA) were established as metabolites with significant change in AP-naïve FEP patients compared to CSs. The following 0.6-year treatment restored these alterations. However, further continuous 5.1-year AP treatment changed the metabolic profile substantially. Significantly elevated levels of asparagine, glutamine, methionine, ornithine and taurine, alongside with decreased levels of aspartate, glutamate and alpha-AAA were observed in the patient group compared to CSs. These biomolecule profile alterations provide further insights into the pathophysiology of SCH spectrum disorders and broaden our understanding of the impact of AP treatment in the early stages of the disease

The Expanded Endocannabinoid System Contributes to Metabolic and Body Mass Shifts in First-Episode Schizophrenia: A 5-Year Follow-Up Study

Alterations in the expanded endocannabinoid system (eECS) and cell membrane composition have been implicated in the pathophysiology of schizophrenia spectrum disorders. We enrolled 54 antipsychotic (AP)-naïve first-episode psychosis (FEP) patients and 58 controls and applied a targeted metabolomics approach followed by multivariate data analysis to investigate the profile changes in the serum levels of endocannabinoids: 2-arachidonoylglycerol (2-AG) and anandamide, endocannabinoids-like N-acylethanolamines (NAEs: linoleoylethanolamide, oleoylethanolamide, and palmitoylethanolamide), and their dominating lipid precursor’s phosphatidylcholines. Biomolecule profiles were measured at the onset of first-episode psychosis (FEP) and 0.6 years and 5.1 years after the initiation of AP treatment. The results indicated that FEP might be characterized by elevated concentrations of NAEs and by decreased 2-AG levels. At this stage of the disease, the NAE-mediated upregulation of peroxisome proliferator-activated receptors (PPARs) manifested themselves in energy expenditure. A 5-year disease progression and AP treatment adverse effects led to a robust increase in 2-AG levels, which contributed to strengthened cannabinoid (CB1) receptor-mediated effects, which manifested in obesity. Dynamic 2-AG, NAEs, and their precursors in terms of phosphatidylcholines are relevant to the description of the metabolic shifts resulting from the altered eECS function during and after FEP