Serotonin transporter density in isolated rapid eye movement sleep behavioral disorder.

Background/objective: The serotoninergic nervous system is known to play a role in the maintenance of rapid eye movement (REM) sleep. Serotoninergic projections are known to be vulnerable in synucleinopathies. To date, positron emission tomography (PET) studies using serotonin-specific tracers have not been reported in isolated REM sleep behavior disorder (iRBD).
Methods: We conducted a cross-sectional imaging study using serotonin transporter (SERT) ¹¹ C-3-amino-4-(2-dimethylaminomethyl-phenylsulfaryl)-benzonitrile (DASB) PET to identify differences in serotonin system integrity between 11 participants with iRBD and 16 older healthy controls.
Results: Participants with iRBD showed lower DASB distribution volume ratios (DVRs) in the total neocortical mantle [1.13 (SD: 0.07) vs. 1.19 (SD: 0.06); t = 2.33, p = 0.028)], putamen [2.07 (SD: 0.19) vs. 2.25 (SD: 0.18); t = 2.55, p = 0.017], and insula [1.26 (SD: 0.11) vs. 1.39 (SD: 0.09); t = 3.58, p = 0.001]. Paradoxical increases relative to controls were seen in cerebellar hemispheres [0.98 (SD: 0.04) vs. 0.95 (SD: 0.02); t = 2.93, p = 0.007)]. No intergroup differences were seen in caudate, substantia nigra, or other brainstem regions with the exception of the dorsal mesencephalic raphe [3.08 (SD: 0.53) vs. 3.47 (SD: 0.48); t = 2.00, p = 0.056] that showed a non-significant trend toward lower values in iRBD.
Conclusions: Insular, neocortical, and striatal serotoninergic terminal loss may be common in prodromal synucleinopathies before the onset of parkinsonism or dementia. Given our small sample size, these results should be interpreted as hypothesis-generating/exploratory in nature.
Competing Interests: MG serves as a coinvestigator with effort for the Parkinson Progression Markers Initiative 2.0 (PPMI 2.0) project. NB has received research funding from the National Institutes of Health (P50 NS123067, R01 AG073100, U01 AG061393), Department of Affairs (I01 RX001631), Parkinson’s Foundation, the Farmer Family Foundation Parkinson’s Research Initiative, and the Michael J. Fox Foundation. VK receives payment and a travel stipend from the Movement Disorders Society for his role as an Associate Editor on the journal Movement Disorders and receives research grant funding from the US National Institutes of Health (NIH) and the US Department of Veterans Affairs (VA). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.