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

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