Neuropsychological performance and noradrenaline function in chronic fatigue syndrome under conditions of high arousal

Rationale: Subjective and objective impairments in neuropsychological function have been reported in chronic fatigue syndrome (CFS) patients under conditions of high arousal. These impairments may reflect impaired central noradrenaline function such as impaired post-synaptic alpha-2 adrenoceptor function. Objectives: To determine whether high-dose clonidine has greater agonist effects at central post-synaptic alpha-2 receptors in CFS patients than controls under conditions of high arousal. As a result clonidine may reverse neuropsychological deficits underlying symptoms of poor concentration and memory. Methods: High-dose clonidine (2.5 mg/kg) and placebo challenge tests were given in random order to ten medication-free CFS patients without anxiety disorders, depressive disorders or migraine and ten matched healthy controls under the same stressors (timed neuropsychological testing, venous sampling, intravenous drug administration). Growth hormone, cortisol, blood pressure, pulse rate, visual analogue scales of subjective neuropsychological performance and the performance on several tests from a computerised neuropsychological battery were measured. Results: In CFS patients versus controls, clonidine enhanced both growth hormone (P=0.028) and cortisol release (P=0.021) and increased speed in the initial stage of a planning task (P=0.023). There were no other differences between CFS patients and controls on hormonal, physiological, symptomatic or neuropsychological measures. Conclusions: Under conditions of high arousal, CFS patients may display supersensitive central post-synaptic alpha-2 adrenoceptor function associated with the release of cortisol and growth hormone and initial thinking time in planning tasks.