Ferroptosis as a potential connection between schizophrenia and metabolic dysfunction-associated steatotic liver disease – a narrative review

Purpose
Schizophrenia is a chronic condition that is associated with various comorbidities, including metabolic ones. Particular attention has been paid to the metabolic dysfunction-associated steatotic liver disease (MASLD), the liver equivalent of the metabolic syndrome. It is postulated that ferroptosis, a form of novel cell death connected with iron overload and lipid peroxidation, may be an interplaying factor in both of these conditions. This review aims to show the specific role of ferroptosis in the development and possible progression of MASLD among patients with schizophrenia. It will be accompanied by a consideration of the probable causes of the associations that occur.

Views
Scientific reports suggest that there may be a genetic predisposition, in terms of ferroptosis, to the development of both schizophrenia and MASLD. Moreover, the role of poor dietary habits, specifically a high-fat diet and insufficient antioxidant intake, in excessive lipid peroxidation and iron overload is emphasized. Additionally, intestinal permeability, caused by iron overload, may contribute to a state of inflammation within the liver tissue. Finally, we cannot forget about the impact of antipsychotic drugs on the ferroptosis process – some of them may initiate this process through carbohydrate-lipid metabolism dysregulation, or causing hepatocyte iron overload, as well as disturbing cellular redox balance.

Conclusions
The process of ferroptosis should be considered as one of the possible pathways which predispose a group of patients with schizophrenia to the development and progression of MASLD. Finding a possible marker of ferroptosis among the mentally ill population may be helpful in the identification of a subgroup of patients particularly vulnerable to steatotic liver disease.