Tremor in Parkinson's disease and serotonergic dysfunction: an 11C-WAY 100635 PET study.
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-HT(1A) binding provides a functional measure of serotonergic system integrity. With PET, the aim of this study was to examine regional cerebral (11)C-WAY 100635 binding to 5-HT(1A) receptors in patients with PD and to correlate it with severity of tremor.


METHODS
(11)C-WAY 100635 PET was performed on 23 patients with PD and eight age-matched healthy volunteers. Brain 5-HT(1A) 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-HT(1A) 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-HT(1A) 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-HT(1A) binding represents receptor dysfunction or loss of cell bodies due to Lewy body degeneration in PD, or both. An association between 5-HT(1A) receptor availability in the raphe and severity of parkinsonian tremor was also found.
Doder
M
M
Division of Neuroscience and MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College, London, UK. m.doder@ic.ac.uk
Rabiner
E A
EA
Turjanski
N
N
Lees
A J
AJ
Brooks
D J
DJ
D002250:Carbon Radioisotopes; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000150:complications / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D010879:Piperazines; D011725:Pyridines; D011903:Raphe Nuclei / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D058829:Serotonin 5-HT1 Receptor Antagonists; D012702:Serotonin Antagonists; D014055:Tomography, Emission-Computed; D014202:Tremor / Q000175:diagnosis / Q000209:etiology / Q000503:physiopathology*
D002250:Carbon Radioisotopes; D010879:Piperazines; D011725:Pyridines; D058829:Serotonin 5-HT1 Receptor Antagonists; D012702:Serotonin Antagonists; D044282:Receptor, Serotonin, 5-HT1A; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide