Elsevier

Biological Psychiatry

Volume 57, Issue 3, 1 February 2005, Pages 239-246
Biological Psychiatry

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

https://doi.org/10.1016/j.biopsych.2004.10.031Get rights and content

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.

Section snippets

Subjects

Ten patients (eight men and two women) with chronic fatigue syndrome were recruited from an established CFS referral clinic at King-s College Hospital, London (Table 1). All clinic attenders were assessed using a thorough semistructured examination (Sharpe et al 1997a) at initial consultation to evaluate CFS and the presence of additional psychiatric disorder. Patients were included if they fulfilled both international consensus criteria for CFS (i.e., the Oxford criteria; Sharpe et al 1991)

Binding potential

To explore the effects of subject group and region on BP measures, we entered all 41 ROI measurements (left and right values for 20 brain areas and the raphe nuclei) into a repeated-measures ANOVA with region as the within-subject factor and group as the between-subjects factor. To explore the effects of laterality, we entered only the 40 ROI measures that were bilateral (i.e., the raphe measure was excluded) and added laterality as an additional, binary, within subject factor; because this

Discussion

The main finding from this study is of a widespread reduction in BP values for [11C]WAY-100635 in a carefully selected group of medication-free patients with CFS and no current comorbid psychiatric disorder, including depression. This reduction was particularly marked in the hippocampus bilaterally. This is the first study to our knowledge that has used neuroimaging to measure 5-HT receptors in CFS.

The reduced BP observed with [11C]WAY 100635 suggests either a reduction in the number of 5-HT1A

References (44)

  • E.A. Rabiner et al.

    A Database of [11C]WAY-100635 binding to 5-HT1A receptors in normal male volunteersNormative data and relationship to methodological, demographic, physiological, and behavioral variables

    Neuroimage

    (2002)
  • M. Sharpe et al.

    Chronic fatigue syndrome. A practical guide to assessment and management

    Gen Hosp Psychiatry

    (1997)
  • M. Sharpe et al.

    Increased prolactin response to buspirone in chronic fatigue syndrome

    J Affect Disord

    (1996)
  • M. Slifstein et al.

    Derivation of [(11)C]WAY-100635 binding parameters with reference tissue modelsEffect of violations of model assumptions

    Nucl Med Biol

    (2000)
  • J.H. Vercoulen et al.

    Physical activity in chronic fatigue syndromeassessment and its role in fatigue

    J Psychiatr Res

    (1997)
  • S. Wessely et al.

    Post infectious fatigueA prospective study in primary care

    Lancet

    (1995)
  • F. Yasuno et al.

    Decreased 5-HT1A receptor binding in amygdala of schizophrenia

    Biol Psychiatry

    (2004)
  • A. Bakheit et al.

    Possible upregulation of hypothalamic 5-hydroxytryptamine receptors in patients with postviral fatigue syndrome

    BMJ

    (1992)
  • Z. Bhagwagar et al.

    Persistent reduction in brain serotonin(1A) receptor binding in recovered depressed men measured by positron emission tomography with [(11)C]WAY-100635

    Mol Psychiatry

    (2004)
  • E. Blomstrand et al.

    Changes in plasma concentrations of aromatic and branched-chain amino acids during sustained exercise in man and their possible role in fatigue

    Acta Physiol Scand

    (1988)
  • J. Brooks et al.

    Proton magnetic resonance spectroscopy and morphometry of the hippocampus in chronic fatigue syndrome

    Br J Radiol

    (2000)
  • S. Campbell et al.

    Lower hippocampal volume in patients suffering from depressionA meta-analysis

    Am J Psychiatry

    (2004)
  • Cited by (100)

    • Association of HTR2A-1438G/A Genetic Polymorphism With Smoking and Chronic Obstructive Pulmonary Disease

      2019, Archivos de Bronconeumologia
      Citation Excerpt :

      The A allele of rs6311 increases promotor activity, mRNA expression and protein levels and increases receptor binding.29,30 This promoter polymorphism supports an hyperactive serotonergic system.31 In addition, Falkerlber et al. suggested that the promoter polymorphism (rs6311) can affect both transcription factor binding and promoter methylation, and this along with an individual's stress response can impact the rate of HTR2A transcription in a genotype and methylation-dependent manner.32

    View all citing articles on Scopus
    View full text