Depression, evening salivary cortisol and inflammation in chronic fatigue syndrome: A psychoneuroendocrinological structural regression model

Introduction: Chronic Fatigue Syndrome (CFS) is a poorly understood illness that is characterized by diverse somatic symptoms, hypothalamic pituitary adrenal (HPA) axis dysfunction and heightened inflammatory indicators. These symptoms are often exacerbated and accompanied by psychological distress states and depression. Since depression is known to be associated with HPA axis dysfunction and greater inflammation, a psychoneuroendocrinological (PNE) model of inflammation was examined in persons diagnosed with CFS in order to uncover underlying biopsychosocial mechanisms in this poorly understood chronic illness. Methods: Baseline data were drawn from two randomized controlled trials testing the efficacy of different forms of psychosocial intervention, and included psychological questionnaires, di-urnal salivary cortisol, and blood samples. Data were analyzed with structural equation modeling (SEM). Results: The sample (N = 265) was mostly middle-aged (M-age = 49.36 +/- 10.9, range = 20-73 years), Caucasian (67.7%), female (81.7%), highly educated (85.5% completed some college, college, or graduate program), and depressed (CES-D M = 23.87 +/- 12.02, range 2-57). The SEM supporting a psychoneuroendocrinological model of immune dysregulation in CFS fit the data chi(2) (12) = 17.725, p = 0.1243, RMSEA = 0.043, CFI = 0.935, SRMR = 0.036. Depression was directly related to evening salivary cortisol and inflammation, such that higher evening cortisol predicted greater depressive symptoms (beta = 0.215, p < 0.01) and higher pro-inflammatory cytokines (interleukin-2 [IL-2], IL-6, and tumor necrosis factor-alpha [TNF-alpha] levels (beta = 0.185, p < 0.05), when controlling for covariates. Discussion: Results highlight the role of depression, cortisol and inflammation in possible biological mechanisms involved in the pathophysiology of CFS. Time-lagged, longitudinal analyses are needed to fully explore these relationships.