Biomarkers of depression in cancer patients

Abstract

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.

Suppression of negative affect in cancer patients. Trauma and defensiveness of self-esteem as predictors of depression and anxiety

“…This "bodymind" discrepancy is probably due to the denial of the negative affect, as too difficult to adapt to (or accept). The physiological indications are consistent with therapists' observation of excessive, difficult to control responses of cancer sufferers to fearful events, as well as with data showing that 30-40% of patients suffering from cancer simultaneously suffer depression and anxiety disorders (Bucceri, 1998;Jehn et al, 2006;Stommel, Given, & Given, 2002). The concept of "cancer proneness," "cancerous personality" or "personality susceptible to immunosuppression" assumes the tendency to repress emotional reactions to difficult life events (Dattore et al, 1980;Eysenc, 1985;Watson, Pettingale, & Greer, 1984).…”

Neuroendocrine-Immune Mechanisms of Behavioral Comorbidities in Patients With Cancer

“…[49][50][51][52] Relevant to the role of the immune system in depression in cancer patients, increased plasma concentrations of IL-6, have been found in two separate studies in cancer patients diagnosed with major depression (Table 1). 53,54 Nevertheless, results have been inconsistent, especially in studies looking at correlations between inflammatory biomarkers and depressive symptoms (as measured by standardized depression rating scales). Of note, however, there is a surprising paucity of studies on depressed cancer patients compared to the rich literature examining patients with other medical illnesses, including cardiovascular disease, as well as healthy depressed subjects, where a large number of studies have revealed a clear relationship between inflammatory markers and both a diagnosis of major depression and depressive symptom severity.…”

138. Cortisol and inflammatory processes in ovarian cancer patients following primary treatment: Relationships with depression, fatigue, and disability

“…(Conti et al 2004;Terreni & De Simoni, 1998) and IL-6 has been linked to depressive spectrum behaviors characterized as "sickness behaviors" (Dantzer et al, 2002;Dantzer, 2006). Both IL-6 and hypercortisolemia have been linked to depression (Dowlati et al, 2010;Howren et al 2009;Liu et al 2011;Lopez-Duran et al 2009;Stetler & Miller, 2011) and disruption of cortisol rhythms has been linked to depression in breast and ovarian cancer populations (Abercrombie et al 2004;Jehn et al 2006);Lutgendorf et al 2008;Weinrib et al 2010) It is possible that the residual tumor mass may have affected both inflammatory pathways and self-reported functional outcomes. However, extent of surgical resection was not significantly associated with reduction of inflammation.…”