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Review
. 2012 Nov;26(8):1202-10.
doi: 10.1016/j.bbi.2012.06.006. Epub 2012 Jun 23.

Biomarkers for chronic fatigue

Nancy G Klimas  1 , Gordon Broderick, Mary Ann Fletcher
Affiliations
Review

Biomarkers for chronic fatigue

Nancy G Klimas et al. Brain Behav Immun. 2012 Nov.

Abstract

Fatigue that persists for 6 months or more is termed chronic fatigue. Chronic fatigue (CF) in combination with a minimum of 4 of 8 symptoms and the absence of diseases that could explain these symptoms, constitute the case definition for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). Inflammation, immune system activation, autonomic dysfunction, impaired functioning in the hypothalamic-pituitary-adrenal axis, and neuroendocrine dysregulation have all been suggested as root causes of fatigue. The identification of objective markers consistently associated with CFS/ME is an important goal in relation to diagnosis and treatment, as the current case definitions are based entirely on physical signs and symptoms. This review is focused on the recent literature related to biomarkers for fatigue associated with CFS/ME and, for comparison, those associated with other diseases. These markers are distributed across several of the body's core regulatory systems. A complex construct of symptoms emerges from alterations and/or dysfunctions in the nervous, endocrine and immune systems. We propose that new insight will depend on our ability to develop and deploy an integrative profiling of CFS/ME pathogenesis at the molecular level. Until such a molecular signature is obtained efforts to develop effective treatments will continue to be severely limited.

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Figures

Figure 1
Figure 1. Networks of cytokine association show visibly different topologies
A weighted spring-electrical embedding structurally reveals the subject–subject (inset) and cytokine–cytokine associations based on measurements in 59 healthy control subjects (a) and 40 CFS/ME patients (b). All edge weights are significant at p ⩽ 0.01. Separation of subjects was consistent with their assignment to diagnostic groups supporting the use of within-group variation in the estimation of mutual information for cytokine–cytokine associations.
Figure 2
Figure 2
Diagrammatic representation of the hypothesis whereby two complex and very distinct illnesses CFS/ME and cancer-related fatigue occupy distinct energy-minimal equilibrium points characterized by alternative configurations of the neuroendocrine-immune biomarker and symptom association networks.
See this image and copyright information in PMC

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