Tremor in Parkinson's disease and serotonergic dysfunction: An 11C-WAY 100635 PET study

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  • M. Doder, Imperial College London, London, UK., Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, Hammersmith Hospital
  • ,
  • E. A. Rabiner, Imperial College London, London, UK.
  • ,
  • N. Turjanski, Imperial College London, London, UK.
  • ,
  • A. J. Lees, Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London
  • ,
  • D. J. Brooks

Background: The pathophysiologic mechanisms underlying parkinsonian tremor remain unclear. The response to dopaminergic treatment is variable and nondopaminergic mechanisms may play a role in tremor generation. Midbrain raphe 5-HT1A binding provides a functional measure of serotonergic system integrity. With PET, the aim of this study was to examine regional cerebral 11C-WAY 100635 binding to 5-HT1A receptors in patients with PD and to correlate it with severity of tremor. Methods: 11C-WAY 100635 PET was performed on 23 patients with PD and eight age-matched healthy volunteers. Brain 5-HT1A receptor binding was computed using compartmental modeling with a cerebellar reference tissue input function. Results: The authors found mean 27% reduction in the midbrain raphe 5-HT1A binding potential in patients with PD compared to healthy volunteers (p < 0.001). They also showed that Unified Parkinson's Disease Rating Scale composite tremor scores, but not rigidity or bradykinesia, correlate with 5-HT1A binding in the raphe (p < 0.01). Conclusions: These findings support previous indirect evidence that serotonergic neurotransmission is decreased in PD in vivo. The authors hypothesize that the reduction in raphe 5-HT1A binding represents receptor dysfunction or loss of cell bodies due to Lewy body degeneration in PD, or both. An association between 5-HT1A receptor availability in the raphe and severity of parkinsonian tremor was also found.

Original languageEnglish
JournalNeurology
Volume60
Issue4
Pages (from-to)601-605
Number of pages5
ISSN0028-3878
DOIs
Publication statusPublished - 25 Feb 2003
Externally publishedYes

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