Chronic fatigue syndrome: new evidence for a central fatigue disorder.

Clin Sci (Lond) 2003 Apr 23; [epub ahead of print]

Authors: Georgiades E, Behan WM, Kilduff LP, Hadjicharalambous M, Mackie
EE, Wilson J, Ward SA, Pitsiladis YP.

Affiliation: Centre for Exercise Science and Medicine, Institute of
biomedical and life sciences, University of Glasgow, GLASGOW G12 8QQ,
United Kingdom.

Received 11 December 2002/19 March 2003; Accepted 23 April 2003
Published as Immediate Publication 23 April 2003

NLM Citation: PMID: 12708966

Considerable evidence points towards a prominent role for central neural
(CNS) mechanisms in the pathogenesis of chronic fatigue syndrome (CFS), a
disorder characterised chiefly by persistent, often debilitating, fatigue. We wished to characterise circulating profiles of putative amino acid modulators of CNS serotoninergic and dopaminergic function in CFS patients at rest, during symptom-limited exercise and subsequent recovery.

Twelve CFS patients and eleven age- and sex-matched sedentary controls, with similar physical activity histories, underwent ramp-incremental exercise to the limit of tolerance. Plasma amino acid concentrations, oxygen uptake (Vo 2) and ratings of perceived exertion (RPE) were measured at rest, during exercise and recovery.

Peak oxygen uptake (Vo 2peak) was significantly lower in the CFS patients, compared to controls. RPE in the patients was higher at all measured time points, including rest, relative to controls. Levels of free tryptophan [free Trp], the rate-limiting serotoninergic precursor, were significantly higher in CFS patients at exhaustion and recovery,
whereas concentrations of branched-chain and large-neutral amino acids (BCAA and LNAA, respectively) were lower in patients at exhaustion and, for [LNAA], also during recovery.

Consequently, the [free Trp] : [BCAA] and [free Trp] : [LNAA] ratios were significantly higher in CFS patients, except at rest. On the other hand, levels of tyrosine, the rate-limiting dopaminergic precursor, were significantly lower at all time points in the patients.

The significant differences observed in a number of key putative CNS serotoninergic and dopaminergic modulators, coupled with the exacerbated effort perception, provide further evidence for a potentially significant role of CNS mechanisms in CFS pathogenesis.