Compromised hepatic bilirubin clearance drives depressive symptoms via regulating microglial engulfment of dendritic spines.

ABSTRACT:

Background

Major depressive disorder (MDD) remains a debilitating global health issue with limited treatment efficacy. Liver qi stagnation (or called liver depression) has been associated with MDD, but the underlying mechanisms are poorly understood. This study investigates whether impaired hepatic function contributes to depressive symptomatology.

Methods

Using retrospective clinical data, chronic unpredictable stress (CUMS) models, orthotopic liver transplantation, and microglia-specific genetic tools (including TRPM2 and SYK conditional knockouts), we combined behavioral assays, multi-omics, electrophysiology, and optogenetics to explore the liver-brain axis in depression.

Results

Compromised hepatic bilirubin clearance in depressive subjects drives depressive symp

SUBMITTER: Sun S 

PROVIDER: S-EPMC12829269 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature