Abstract
The hypothalamic-pituitary-adrenal (HPA) axis is a psychoneuroendocrine regulator of the stress response and immune system, and dysfunctions have been associated with outcomes in several physical health conditions. Its end product, cortisol, is relevant to fatigue due to its role in energy metabolism. The systematic review examined the relationship between different markers of unstimulated salivary cortisol activity in everyday life in chronic fatigue syndrome (CFS) and fatigue assessed in other clinical and general populations. Search terms for the review related to salivary cortisol assessments, everyday life contexts, and fatigue. All eligible studies (n=19) were reviewed narratively in terms of associations between fatigue and assessed cortisol markers, including the cortisol awakening response (CAR), circadian profile (CP) output, and diurnal cortisol slope (DCS). Subset meta-analyses were conducted of case-control CFS studies examining group differences in three cortisol outcomes: CAR output; CAR increase; and CP output. Meta-analyses revealed an attenuation of the CAR increase within CFS compared to controls (d=-.34) but no statistically significant differences between groups for other markers. In the narrative review, total cortisol output (CAR or CP) was rarely associated with fatigue in any population; CAR increase and DCS were most relevant. Outcomes reflecting within-day change in cortisol levels (CAR increase; DCS) may be the most relevant to fatigue experience, and future research in this area should report at least one such marker. Results should be considered with caution due to heterogeneity in one meta-analysis and the small number of studies.
Highlights
MethodsThe following data were extracted: (1) author; (2) year; (3) definition of fatigue, if given; (4) study design (case/control, etc.); (5) participant characteristics (population; number; age; gender; criteria for inclusion/exclusion); (6) number and timing of cortisol assessments; (7) number of sampling days; (8) method of maximizing compliance, if any; (9) saliva sampling procedure; (10) behavioral instructions around saliva sampling; (11) cortisol assay used; (12) chosen fatigue measure; (13) facets of fatigue experience measured (for example, physical or mental fatigue components); (14) variables controlled in the analyses; (15) mean/SD of cortisol assessments and/or computations; (16) mean/SD of fatigue measures; (17) statistical analysis used; (18) results and conclusions
The present review examined studies of different CSA markers operationalized by saliva sampling in everyday life and their respective relationships with fatigue in (1) chronic fatigue syndrome (CFS); (2) other clinical groups; and (3) nonclinical populations
We found an attenuation of cortisol diurnal variability to be important in relation to fatigue in most constituent studies
Summary
The following data were extracted: (1) author; (2) year; (3) definition of fatigue, if given; (4) study design (case/control, etc.); (5) participant characteristics (population; number; age; gender; criteria for inclusion/exclusion); (6) number and timing of cortisol assessments; (7) number of sampling days; (8) method of maximizing compliance, if any; (9) saliva sampling procedure; (10) behavioral instructions around saliva sampling; (11) cortisol assay used; (12) chosen fatigue measure; (13) facets of fatigue experience measured (for example, physical or mental fatigue components); (14) variables controlled in the analyses; (15) mean/SD of cortisol assessments and/or computations; (16) mean/SD of fatigue measures; (17) statistical analysis used; (18) results and conclusions.
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