Psychological Medicine

Original Article

Decreased tryptophan availability but normal post-synaptic 5-HT2c receptor sensitivity in chronic fatigue syndrome

C. M.  VASSALLO  a1, E.  FELDMAN  a1, T.  PETO  a1, L.  CASTELL  a1, A. L.  SHARPLEY  a1 and P. J.  COWEN  a1 c1
a1 From the University Department of Psychiatry, Warneford Hospital: Department of Biochemistry, University of Oxford, Department of Psychological Medicine and Nuffield Department of Medicine, John Radcliffe Hospital, Oxford


Background. Chronic fatigue syndrome (CFS) has been associated with increased prolactin (PRL) responses to the serotonin (5-HT) releasing agent fenfluramine. It is not known whether this abnormality is due to increased 5-HT release or heightened sensitivity of post-synaptic 5-HT receptors.

Methods. We measured the increase in plasma PRL produced by the directly acting 5-HT receptor agonist, m-chlorophenylpiperazine (mCPP), in patients with CFS and healthy controls. We also compared the ability of mCPP to lower slow wave sleep (SWS) in the sleep polysomnogram of both subject groups. Finally, we measured plasma amino-acid levels to determine whether tryptophan availability differed between CFS subjects and controls.

Results. mCPP elevated plasma PRL equivalently in patients with CFS and controls. Similarly, the decrease in SWS produced by mCPP did not differ between the two subject groups. Plasma-free tryptophan was significantly decreased in CFS.

Conclusions. The sensitivity of post-synaptic 5-HT2c receptors is not increased in patients with CFS. This suggests that the increased PRL response to fenfluramine in CFS is due to elevated activity of pre-synaptic 5-HT neurones. This change is unlikely to be due to increased peripheral availability of tryptophan.

c1 Address for correspondence: Professor P. J. Cowen, University Department of Psychiatry, Warneford Hospital, Oxford OX3 7JX.