title: 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.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Psychology & Comprehensive Cancer Center, Ohio State University, 1835 Neil Avenue, Columbus, OH 43210, USA. thornton.84@osu.edu
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Thornton
authors.forename: Barbara L
authors.initials: BL
authors.lastname: Andersen
authors.forename: Wendy P
authors.initials: WP
authors.lastname: Blakely
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000150:complications / Q000503:physiopathology / Q000523:psychology*; D003430:Cross-Sectional Studies; D003863:Depression / Q000150:complications / Q000523:psychology*; D004837:Epinephrine / Q000097:blood; D005221:Fatigue / Q000150:complications / Q000523:psychology*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology*; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood; D010146:Pain / Q000150:complications / Q000523:psychology*; D010913:Pituitary-Adrenal System / Q000503:physiopathology*; D011569:Psychiatric Status Rating Scales; D013564:Sympathetic Nervous System / Q000503:physiopathology*
chemical_list: D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone; D009638:Norepinephrine; D004837:Epinephrine