BACKGROUND. Inflammation and perturbation of the hypothalamic‐pituitary‐adrenal (HPA) axis function appears to play a putative role in the etiology of depression. Patients with metastatic cancer demonstrate elevated prevalence rates for depression. The objective of the current study was to illustrate the efficacy of interleukin‐6 (IL‐6) and HPA axis function as adjuncts to support the diagnosis of depression in cancer patients. METHODS. Plasma concentrations of IL‐6 and cortisol were measured in 114 cancer patients with and without depression. The relative diurnal variation of cortisol (cortisol VAR), expressed as a percentage, was calculated. Receiver operating characteristics analysis was performed. RESULTS. Depression was associated with increased plasma concentrations of IL‐6 (18.7 pg/mL vs. 2.7 pg/mL; P < .001) and higher cortisol concentrations at 8 AM and 8 PM. The relative cortisol VAR (11.7% vs. 60.6%, respectively; P < .001) was found to be decreased in cancer patients with depression, indicating a disturbed circadian function of the HPA axis. As a biomarker of depression, IL‐6 yielded at a cutoff value of 10.6 pg/mL, a sensitivity of 79%, and a specificity of 87% (area under the curve [AUC] = 0.86; 95% confidence interval [95% CI], 0.78–0.94), whereas cortisol VAR demonstrated a sensitivity of 81% and a specificity of 88% (AUC = 0.85; 95% CI, 0.74–0.97) at a cutoff value of 33.5%. CONCLUSIONS. Depression is associated with increased plasma IL‐6 concentrations in patients with cancer. These patients demonstrate a dysfunction of the HPA‐axis, characterized by a decreased diurnal variation of cortisol. The high sensitivity and specificity of these parameters biomarkers of depression make IL‐6 and cortisol VAR helpful tools in the diagnosis of depression in patients with cancer. Cancer 2006. © 2006 American Cancer Society.
Depression in cancer is associated with increased plasma IL-6 concentrations and dysfunction of the HPA axis.
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