The pain, depression, and fatigue symptom cluster in advanced breast cancer: covariation with the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system

Abstract

Objective: Neuroendocrine-immune models have been proposed to account for the frequent co-occurrence of pain, depression, and fatigue (PDF) among cancer patients.

Design: In a cross-sectional observational study of advanced cancer patients (N = 104), we tested the hypothesis that the PDF cluster covaries with proposed biological mediators: hormones of the sympathetic nervous system (SNS) and the hypothalamic-pituitary-adrenal (HPA) axis.

Main outcome measures: PDF symptoms were measured using the Brief Pain Inventory, Fatigue Symptom Inventory, and the Center for Epidemiological Studies Depression scales. HPA activation was indicated by plasma levels of cortisol and adrenocorticotropic hormone, and SNS activation was indicated by plasma epinephrine and norepinephrine.

Results: Preliminary analyses supported the use of covariance structure modeling to test whether shared variance among hormone levels predicted shared variance among PDF symptoms. Latent variable analysis indicated that neuroendocrine levels predicted PDF (standardized beta = .23, p = .039), while controlling for important disease and demographic variables.

Conclusion: Previous studies have linked individual symptoms to individual biomarkers. The observed significant paring of the 4 hormones to the PDF cluster provides the first evidence suggestive of stress hormones as a common mechanism for the co-occurrence of pain, depression, and fatigue symptoms.

Figure 1

Structural equation model testing the relationship between the SNS and HPA axes and the pain, depression, and fatigue (PDF) symptom cluster. Note: ACTH=adrenocorticotropic hormone, HPA=hypothalamic-pituitary-adrenal axis, PDF=pain, depression, and fatigue, CES-D=Center for Epidemiological Studies – Depression Scale, KPS=Karnofsky Performance Status scale. * p < .05 ** p < .001