Work

Clinical and molecular implications of antipsychotics in MASLD

Year: 2025

Type: article

Abstract: Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), has emerged as a major comorbidity among patients with severe mental illness (SMI), particularly those treated with second-generation antipsychotics (SGAs). These agents induce systemic metabolic disturbances through mechanisms involving adipose tissue dysfunction, mitochondrial injury, and dysregulation of hepatic lipid metabolism. Increasing evidence identifies SGAs as significant contributors to hepatic dysfunction, acting through activation of sterol regulatory element-binding proteins (SREBPs), impairment of mitochondrial respiratory function, low-grade inflammation, alterations in the AMPK signaling pathway, and gut microbiota dysbiosis. Collectively, these processes promote hepatic lipid accumulation, insulin resistance, and progression toward non-alcoholic steatohepatitis (NASH). Furthermore, non-invasive biomarkers such as the Fatty Liver Index (FLI) and FIB-4 score have demonstrated potential utility for early screening and risk stratification in psychiatric populations. Overall, SGAs play a central role in the pathogenesis of MASLD by disrupting mitochondrial homeostasis, lipid metabolism, and gut-liver axis communication. Routine liver monitoring should be integrated into psychiatric care, and future research must focus on preventive and therapeutic strategies that protect hepatic function without compromising mental stability.

Source: Annals of Hepatology

DOI: 10.1016/j.aohep.2025.102158

Authors: Celina Gonzalez-Peña, Misael Uribe, Norberto C. Chavez-Tapia

Institutions: Mexican Social Security Institute, Hospital Médica Sur

Language: English

Topic: Liver Disease Diagnosis and Treatment

Subfield: Epidemiology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $1,500