Chronic fatigue syndrome: Evidence supporting the hypothesis of a behaviorally-activated neuromodulator of fatigue

Barry E. Hurwitz, Kimberly A. Brownley, Mary Ann Fletcher, Nancy G. Klimas

Research output: Contribution to journalReview articlepeer-review

3 Scopus citations


Chronic Fatigue Syndrome (CFS) is a disorder characterized by a prolonged, debilitating fatigue of unknown etiology. In addition, patients with CFS frequently report enhanced fatigue symptoms following even mild physical exertion, and their tolerance for physical exercise is limited relative to healthy individuals. The physiological mechanisms underlying the excessive fatigue and weakness common to this disorder remain an issue of scientific debate. Collectively, the available data suggest that fatigue in CFS is not due to any neuromuscular dysfunction, per se, but possibly is caused or influenced by some centrally acting mediator that is released during behavioral activities that require physical or mental exertion. In addition to persistent fatigue, there is growing evidence that many CFS patients exhibit alterations in hypothalamic-pituitary-adrenal (HPA) axis and autonomic function, including the inability to maintain the blood pressure response to orthostatic challenge. When an individual engages in mental or physical behavioral activation, there is a release of numerous centrally acting neuromodulators, some of which have been postulated to influence fatigue. This paper examines the evidence supporting a common pathway through which these centrally-mediated psychological and autonomic abnormalities may be linked. It is hypothesized that as a consequence of behavioral activation there is an abnormality in neuromodulator release or action in individuals with CFS, and that this abnormal neuromodulator activity results in increased fatigue. Furthermore, it is postulated that the CNS initiates a counter-regulatory mechanism to reduce the activity of those systems responsible for the production of the neuromodulator; and that the consequence of this counter-regulatory maneuver is the prevailing dysregulation of the autonomic and HPA axes and other dysfunctional cardiovascular and immunological sequelae.

Original languageEnglish (US)
Pages (from-to)45-63
Number of pages19
JournalJournal Of Chronic Fatigue Syndrome
Issue number2
StatePublished - Jan 1 2000


  • Adrenal
  • Autonomic
  • Cardiovascular
  • Chronic fatigue syndrome
  • Cytokine
  • Immune
  • Neuromodulator

ASJC Scopus subject areas

  • Neuropsychology and Physiological Psychology


Dive into the research topics of 'Chronic fatigue syndrome: Evidence supporting the hypothesis of a behaviorally-activated neuromodulator of fatigue'. Together they form a unique fingerprint.

Cite this