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Alterations in Diurnal Salivary Cortisol Rhythm in a Population-Based Sample of Cases With Chronic Fatigue Syndrome

Nater, Urs M. PhD; Youngblood, Laura Solomon MPH; Jones, James F. MD; Unger, Elizabeth R. MD, PhD; Miller, Andrew H. MD; Reeves, William C. MD, MSc; Heim, Christine PhD

doi: 10.1097/PSY.0b013e3181651025
Original Articles

Objective: To examine diurnal salivary cortisol rhythms and plasma IL-6 concentrations in persons with chronic fatigue syndrome (CFS), persons not fulfilling a diagnosis of CFS (we term them cases with insufficient symptoms or fatigue, ISF) and nonfatigued controls (NF). Previous studies of CFS patients have implicated the hypothalamic–pituitary–adrenal axis and the immune system in the pathophysiology of CFS, although results have been equivocal.

Methods: Twenty-eight people with CFS, 35 persons with ISF, and 39 NF identified from the general population of Wichita, Kansas, were admitted to a research ward for 2 days. Saliva was collected immediately on awakening (6:30 am), at 08:00 am, 12 noon, 4:00 pm, 8:00 pm and at bedtime (10:00 pm) and plasma was obtained at 7:30 am. Salivary cortisol concentrations were assessed using radioimmunoassay, and plasma IL-6 was measured using sandwich enzyme-linked immunosorbent assay.

Results: People with CFS demonstrated lower salivary cortisol concentrations in the morning and higher salivary cortisol concentrations in the evening compared with both ISF and NF groups indicating a flattening of the diurnal cortisol profile. Mean plasma IL-6 concentrations were highest in CFS compared with the other groups, although these differences were no longer significant after controlling for BMI. Attenuated decline of salivary cortisol concentrations across the day and IL-6 concentration were associated with fatigue symptoms in CFS.

Conclusions: These results suggest an altered diurnal cortisol rhythm and IL-6 concentrations in CFS cases identified from a population-based sample.

CFS = chronic fatigue syndrome; HPA = hypothalamic–pituitary–adrenal axis; IL-6 = interleukin 6; TNF-alpha = tumor necrosis factor alpha; SF-36 = Medical Outcomes Study 36-Item Short-Form Health Survey; MFI = Multidimensional Fatigue Inventory; CDC SI = Centers for Disease Control and Prevention Symptom Inventory; SDS = Self Rating Depression Scale; AUC = area under the curve; DIS = Diagnostic Interview Schedule.

From the Chronic Viral Diseases Branch, Coordinating Center for Infectious Diseases, Centers for Disease Control & Prevention (U.M.N., L.S.Y., J.F.J., E.R.U., W.C.R.), and Department of Psychiatry & Behavioral Sciences, Emory University School of Medicine (U.M.N., A.H.M., C.H.), Atlanta, Georgia.

Address correspondence and reprint requests to William C. Reeves, MD, Centers for Disease Control and Prevention, Mail Stop A-15, Atlanta, GA 30333. E-mail:

Received for publication April 7, 2007; revision received October 4, 2007.

The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the funding agency.

Copyright © 2008 by American Psychosomatic Society
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