Tremor in Parkinson’s disease and serotonergic dysfunction

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 ¹¹C-WAY 100635 binding to 5-HT_1A 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-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.