High-resolution PET imaging reveals subtle impairment of the serotonin transporter in an early non-depressed Parkinson's disease cohort

Purpose The serotonin transporter (SERT) is a biochemical marker for monoaminergic signaling in brain and has been suggested to be involved inthe pathophysiology of Parkinson's disease (PD). The aim of this PET study was to examine SERT availability in relevant brain regions in early stages ofnon-depressed PD patients. Methods In a cross-sectional study, 18 PD patients (13 M/5F, 64 +/- 7 years, range 46-74 years, disease duration 2.9 +/- 2.6 years; UPDRS motor 21.9 +/- 5.2) and 20 age- and gender-matched healthy control (HC) subjects (15 M/5F, 61 +/- 7 years, range 50-72 years) were included. In a subsequent longitudinal phase, ten of the PD patients (7 M/3F, UPDRS motor 20.6 +/- 6.9) underwent a second PET measurement after 18-24 months. After a 3-T MRI acquisition, baseline PET measurements were performed with [C-11]MADAM using a high-resolution research tomograph. The non-displaceablebinding potential (BPND) was chosen as the outcome measure and was estimated at voxel level on wavelet-aided parametric images, by using the Logan graphical analysis and the cerebellum as reference region. A molecular template was generated to visualize and define different subdivisions of the raphe nuclei in the brainstem. Subortical and cortical regions of interest were segmented using FreeSurfer. Univariate analyses and multivariate network analyses were performed on the PET data. Results The univariate region-based analysis showed no differences in SERT levels when the PD patients were compared with the HC neither at baseline or after 2 years of follow-up. The multivariate network analysis also showed no differences at baseline. However, prominent changes in integration and segregation measures were observed at follow-up, indicating a disconnection of the cortical and subcortical regions from the three nuclei of the raphe. Conclusion We conclude that the serotoninergic system in PD patients seems to become involved with a network dysregulation as the disease progresses, suggesting a disturbed serotonergic signaling from raphe nuclei to target subcortical and cortical regions.