Somatic burden versus silent toxicity: Distinct longitudinal pathways linking gastric and hepatic diseases to...

We still don't know much about how diseases of specific digestive organs might lead to depression. We hypothesized that gastric and hepatic diseases contribute to depression through distinct longitudinal pathways due to their biological differences.

We analyzed five waves (2011-2020) of the China Health and Retirement Longitudinal Study (CHARLS), including 24,065 adults aged ≥ 45 years. Participants were classified into control, stomach disease, liver disease, and comorbid groups. We used linear mixed-effects models to examine longitudinal associations with depressive symptoms (CES-D) and causal mediation analyses to assess the roles of physical pain, sleep duration, and systemic inflammation (C-reactive protein).

Over the 9-year follow-up, both stomach disease (β = 2.27, 95% CI: 1.94-2.59) and liver disease (β = 1.39, 95% CI: 0.45-2.32) were associated with higher depressive symptoms. For stomach disease, physical pain and sleep disturbance jointly mediated > 50% of the association. In contrast, these somatic factors did not mediate the liver-depression link. C-reactive protein showed no clinically meaningful mediation for either condition.

Gastric and hepatic diseases showed differential longitudinal associations with depressive symptoms. Stomach disease-associated depression was largely attenuated by somatic burden, whereas the liver-depression association persisted after accounting for measured physical pain and sleep disturbance. These findings suggest potentially distinct pathways, though causality cannot be established and the association was not explained by measured pain and sleep duration in this study; unmeasured somatic symptoms may still contribute. Clinicians should consider proactive depression screening in patients with liver disease even when physical symptoms appear mild.