Clinical and molecular implications of antipsychotics in MASLD

Area of Science:

• Hepatology
• Psychiatry
• Metabolic Disorders

Background:

• Metabolic dysfunction-associated steatotic liver disease (MASLD), previously NAFLD, is a growing concern in severe mental illness (SMI) populations.
• Second-generation antipsychotics (SGAs) are frequently used in SMI and are linked to metabolic disturbances.

Purpose of the Study:

• To investigate the role of SGAs in the pathogenesis of MASLD in patients with SMI.
• To highlight the mechanisms by which SGAs induce hepatic dysfunction and lipid accumulation.

Main Methods:

• Review of current evidence on SGA-induced metabolic dysfunction and liver injury.
• Analysis of molecular mechanisms including SREBP activation, mitochondrial dysfunction, and gut microbiota alterations.
• Discussion of non-invasive biomarkers for MASLD screening in psychiatric patients.

Main Results:

• SGAs contribute to MASLD through adipose tissue dysfunction, mitochondrial injury, and altered hepatic lipid metabolism.
• Key mechanisms include SREBP activation, impaired mitochondrial respiration, inflammation, AMPK pathway changes, and gut dysbiosis.
• Non-invasive markers like FLI and FIB-4 show promise for early detection and risk stratification.

Conclusions:

• SGAs are central to MASLD development in SMI by disrupting mitochondrial homeostasis, lipid metabolism, and the gut-liver axis.
• Integration of routine liver monitoring into psychiatric care is recommended.
• Future research should focus on preventive and therapeutic strategies for hepatic protection in SMI patients on SGAs.