Parkinson’s disease progression is associated with increased putaminal serotonin to dopamine transporter ratio: relevance for dyskinesias (S48.004)

OBJECTIVE: To assess the role of serotonin transporter (SERT) to dopamine transporter (DAT) binding ratios in the development of Levodopa-induced dyskinesias (LIDs) in Parkinson’s disease (PD) patients. BACKGROUND: Serotonergic mechanisms have shown to play a key role in the development of LIDs in patients with PD. Here we hypothesized that an unfavourable serotonin-to-dopamine terminal ratio would be most detrimental for advanced PD patients who develop LIDs, and we sought to investigate this in vivo using specific serotonin and dopamine terminal markers. DESIGN/METHODS: Twenty-eight patients with PD [17 with LIDs (PD duration: 11.4±4.6 years); 11 stable (PD duration:5.7±2.6 years)] and 12 age- and gender-matched healthy controls were studied with [ 11 C]DASB PET and [ 123 I]FP-CIT SPECT, which are respective specific markers of DAT and SERT availability in vivo . We have employed a simplified reference tissue model using cerebellum as the reference tissue for the quantification of [ 11 C]DASB, whereas a semi-quantification approach was used for [ 123 I]FP-CIT data. We have estimated uptake values in the putamen. RESULTS: PD patients showed decreases in [ 123 I]FP-CIT binding (p 11 C]DASB binding (p 11 C]DASB to [ 123 I]FP-CIT binding ratio, whereas in the PD stable group the ratio was increased by 76[percnt], relative to healthy controls. Higher [ 11 C]DASB to [ 123 I]FP-CIT binding ratio correlated with longer disease duration for the 28 PD patients (r=0.52; p<0.01). CONCLUSIONS: SERT to DAT ratio increases as PD progresses and patients experience LIDs. Our findings further support the role of serotonergic terminals within the dopaminergic denervated striatum for the development of LIDs. Study Supported by: The Michael J Fox Foundation for Parkinson9s disease Research Disclosure: Dr. Roussakis has nothing to disclose. Dr. Politis has nothing to disclose. Dr. Towey has nothing to disclose. Dr. Piccini has nothing to disclose.