Association of inflammation with depression in pancreatic ductal adenocarcinoma.

Abstract

e24059 Background: Pancreatic ductal adenocarcinoma (PDAC) exhibits the highest rates of depression, cachexia, and inflammation among cancers. Systemic inflammation has been proposed to be a mechanism of depression. We hypothesized that systemic inflammation, as measured by neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and monocyte-lymphocyte ratio (MLR) levels, contributes to higher depression levels in patients with PDAC. Methods: We conducted a retrospective chart review of biopsy-confirmed PDAC in patients from January 2014 to November 2024 at Memorial Sloan Kettering Cancer Center. Data collected included demographics, comorbidities, BMI, inflammatory markers (NLR, PLR, MLR), and prescription records for psychotropic medications within two years post-biopsy as a proxy for depression. Weight loss was calculated as the difference in BMI between the biopsy date and two months later. Logistic regression models were performed to examine the association between depression and explanatory variables in both univariate and multivariate analyses. Results: Of the N = 1,456 patients (mean age 67 years, 76.3% White, 47.6% female, 75.3% unresectable disease), 11.5% were prescribed psychotropic medications. Patients with depression were older and had a higher proportion of unresectable disease. The depression group had a lower BMI (25.5 vs. 26.2) and higher inflammatory markers (NLR: 5.61 vs. 5.32; MLR: 0.56 vs. 0.51; PLR: 200.5 vs. 199.3) pre-biopsy though these differences were not statistically significant. Post-biopsy, the depression group had significantly lower BMI and higher systemic inflammatory markers (Table). In univariate analysis, older age, unresectable disease, lower BMI, increased weight loss, and higher inflammatory markers were associated with depression (Table). In multivariate analysis, unresectable disease (OR: 1.860, 95% CI: 1.219-2.923), lower BMI (OR: 0.958, 95% CI: 0.921–0.994), and increased NLR (OR: 1.491, 95% CI: 1.061–2.104) were independent predictors of depression. Conclusions: This study highlights a potential association between systemic inflammation, cachexia, advanced disease, and depression in patients with PDAC. Further research is warranted to investigate the inflammatory mechanisms driving neuropsychiatric symptoms in cancer patients, as understanding these biological correlations may guide targeted interventions to improve mental health. OR (95% CI) p Depression vs Non-depression p Age 1.016 (1.001 - 1.033) 0.044 68.6 vs 66.8 0.043 Unresectable 1.658 (1.106 - 2.565) 0.018 82.7% vs 74.3% 0.022 BMI 0.957 (0.923 - 0.991) 0.015 24.21 vs 25.21 0.014 BMI loss >1.3 (vs ≤1.3) 1.445 (1.040 - 2.005) 0.028 1.32 vs 1.01 0.052 NLR >3.8 (vs ≤3.8) 1.557 (1.127 - 2.161) 0.008 5.67 vs 4.69 0.005 MLR >0.38 (vs ≤0.38) 1.775 (1.211 - 2.671) 0.004 0.70 vs 0.61 0.009 PLR >140 (vs ≤140) 1.438 (1.028 - 2.035) 0.037 234.5 vs 200.9 0.007