AUTHOR=Garwood Mark , Vijayakumar Punithavathy , Bohnen Nicolaas I. , Koeppe Robert A. , Kotagal Vikas 

TITLE=Serotonin transporter density in isolated rapid eye movement sleep behavioral disorder

JOURNAL=Frontiers in Sleep

VOLUME=2

YEAR=2024

URL=https://www.frontiersin.org/journals/sleep/articles/10.3389/frsle.2023.1298854

DOI=10.3389/frsle.2023.1298854

ISSN=2813-2890

ABSTRACT=<sec><title>Background/objective</title><p>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).</p></sec><sec><title>Methods</title><p>We conducted a cross-sectional imaging study using serotonin transporter (SERT) <sup>11</sup>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.</p></sec><sec><title>Results</title><p>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); <italic>t</italic> = 2.33, <italic>p</italic> = 0.028)], putamen [2.07 (SD: 0.19) vs. 2.25 (SD: 0.18); <italic>t</italic> = 2.55, <italic>p</italic> = 0.017], and insula [1.26 (SD: 0.11) vs. 1.39 (SD: 0.09); <italic>t</italic> = 3.58, <italic>p</italic> = 0.001]. Paradoxical increases relative to controls were seen in cerebellar hemispheres [0.98 (SD: 0.04) vs. 0.95 (SD: 0.02); <italic>t</italic> = 2.93, <italic>p</italic> = 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); <italic>t</italic> = 2.00, <italic>p</italic> = 0.056] that showed a non-significant trend toward lower values in iRBD.</p></sec><sec><title>Conclusions</title><p>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.</p></sec>