Serotonin-to-dopamine transporter ratios in Parkinson disease Relevance for dyskinesias

Objective: To investigate whether a serotonin-to-dopamine terminal ratio is related to the appearance of dyskinesias in patients with Parkinson disease (PD). Methods: Twenty-eight patients with idiopathic PD (17 with levodopa-induced dyskinesias [LIDs], 11 without dyskinesias) and 12 age-matched healthy controls were studied with PET and 5[C-11]-3-amino-4-(2-dimethylaminomethylphenyl-sulfanyl)-benzonitrile (C-11-DASB) and with SPECT and [I-123]N-w-fluoropropyl-2 beta-carbomethoxy-3 beta-(4-iodophenyl)nortropane (I-123-ioflupane), which are in vivo specific markers of the serotonin and dopamine transporters' availability, respectively. We have employed a simplified reference tissue model for the quantification of C-11-DASB, whereas a semiquantification approach was used for I-123-ioflupane data. We calculated C-11-DASB binding to I-123-ioflupane uptake ratios for the caudate and the putamen. Results: Patients with PD showed striatal decreases in C-11-DASB binding potential (p < 0.01) and in I-123-ioflupane mean uptake (p < 0.001) compared to controls. The mean C-11-DASB binding to I-123-ioflupane uptake ratio in the putamen was 0.779 (increased by 75.8% of the controls' mean) for the nondyskinetic group and 0.901 (increased by 103.4% of the controls' mean) for the patients with dyskinesias. There was a statistically significant difference (p < 0.001) in C-11-DASB binding to I-123-ioflupane uptake ratio in the putamen between the group of patients with and without dyskinesias. Higher C-11-DASB to I-123-ioflupane binding ratios correlated with longer disease duration for the 28 patients with PD (r = 0.52; p < 0.01). Conclusions: Serotonin-to-dopamine transporter binding ratio increases as PD progresses and patients experience LIDs. Our findings suggest that, when the dopaminergic innervation in the striatum is critically low, the serotonergic system plays an important role in development of LIDs.