Brain 5-HT1A receptor binding in chronic fatigue syndrome measured using positron emission tomography and [11C]WAY-100635

Biol Psychiatry. 2005 Feb 1;57(3):239-46. doi: 10.1016/j.biopsych.2004.10.031.


Background: Research from neuroendocrine challenge and other indirect studies has suggested increased central 5-HT function in chronic fatigue syndrome (CFS) and increased 5-HT1A receptor sensitivity. We assessed brain 5-HT1A receptor binding potential directly using the specific radioligand [11C]WAY-100635 and positron emission tomography (PET).

Methods: We selected 10 patients from a tertiary referral clinic who fulfilled the CDC consensus criteria for CFS. To assemble a homogenous group and avoid confounding effects, we enrolled only subjects who were completely medication-free and did not have current comorbid psychiatric illness. We also scanned 10 healthy control subjects.

Results: There was a widespread reduction in 5-HT1A receptor binding potential in CFS relative to control subjects. This was particularly marked in the hippocampus bilaterally, where a 23% reduction was observed.

Conclusions: There is evidence of decreased 5-HT1A receptor number or affinity in CFS. This may be a primary feature of CFS, related to the underlying pathophysiology, or a finding secondary to other processes, such as previous depression, other biological changes or the behavioral consequences of CFS.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Brain Chemistry
  • Brain Mapping
  • Brain* / diagnostic imaging
  • Brain* / drug effects
  • Brain* / metabolism
  • Carbon Isotopes
  • Case-Control Studies
  • Fatigue Syndrome, Chronic / metabolism*
  • Female
  • Humans
  • Image Processing, Computer-Assisted / methods
  • Male
  • Middle Aged
  • Piperazines* / metabolism
  • Positron-Emission Tomography / methods
  • Protein Binding / drug effects
  • Pyridines* / metabolism
  • Receptor, Serotonin, 5-HT1A / metabolism*
  • Serotonin Antagonists* / metabolism


  • Carbon Isotopes
  • Piperazines
  • Pyridines
  • Serotonin Antagonists
  • Receptor, Serotonin, 5-HT1A
  • N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide