Inflammation-associated depression in cholangiocarcinoma: impacts of surgical resection and radiotherapy

Background: Cholangiocarcinoma (CCA) is an aggressive malignancy associated with systemic inflammation and a high psychological burden. However, the relationship between inflammation and depression in CCA remains poorly understood. This study aimed to investigate the association between systemic inflammatory markers and depression in patients with CCA. Methods: We conducted a prospective cohort study of patients aged ≥ 20 years with a diagnosis of cholangiocarcinoma treated at a single tertiary medical center between May 2021 and September 2024. Depression was evaluated using the Patient Health Questionnaire-9. Generalized linear mixed models were applied to examine the relationships between inflammatory markers and depression. Results: A total of 164 patients with CCA were included, comprising 97 intrahepatic cholangiocarcinoma (ICC) and 67 extrahepatic cholangiocarcinoma (ECC) cases. Depression prevalence was 19.9% at baseline and fluctuated over time, ultimately decreasing to 10.4% at 12 months. In multivariate analyses, not receiving surgical resection and higher C-reactive protein (CRP) levels were independently associated with depression in the overall CCA cohort and in the ICC subgroup. In the ECC subgroup, receipt of radiotherapy and lower albumin levels were independently associated with increased depression risk. Conclusions: Our study reveals a significant association between inflammatory markers and depression in CCA patients, with CRP emerging as a key marker. Notably, surgical intervention was associated with a reduced risk of depression, whereas radiotherapy in ECC patients was associated with an increased risk of depression.