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

Abstract

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.

Role of Mitochondria in the Chronification of Inflammation: Focus on Dysfunctional Mitophagy and Mitochondrial DNA Mutations

“…Patients with schizophrenia have a pronounced metabolic inflammatory imbalance, as evidenced by the presence of increased pro-inflammatory activity and obesity with changes in the metabolism of carbohydrates, lipids, and their metabolites. 96 This study showed that adipose tissue accumulation during the disease progression and treatment with antipsychotics affects a number of key homeostatic factors by disrupting the mechanisms responsible for lipid and carbohydrate metabolism and leading to undesirable changes in cytokine and adipokine profiles. The involvement of cytokines and inflammasomes in the process of development of metabolically associated fatty liver disease, which exhibits a robust immune-inflammatory dimension, was demonstrated.…”

“Severe Anemia: A Case Report of an Uncommon Precipitant of Schizophrenia Relapse”

“…[54][55][56][57][58][59] Moreover, the chronic use of antipsychotics and the patient's sedentary lifestyle could have led to metabolic derangements, potentially worsening the inflammatory condition. 60 Her HIV infection, although well controlled, can also exert subtle inflammatory disturbances that chronically deteriorate brain function and adds to the predisposition. 61 These factors are then precipitated into a syndromic relapse by the emergence of severe anemia.…”