Monoaminergic Function and Anxiety, Depression, RBD, and Cognitive Impairment in Parkinson’s Disease
Kalle Niemi1, Valtteri Kaasinen2, Juho Joutsa1
1Turku Brain and Mind Center, University of Turku, 2Neurocenter, Turku University Hospital
Objective:
To investigate the association between monoamine transporter binding and depression, anxiety, REM sleep behavior disorder (RBD) and cognition in early Parkinson’s disease (PD).
Background:
PD is associated with many neuropsychiatric symptoms but the neurobiological mechanisms of these symptoms are unclear. Some of the neuropsychiatric symptoms respond to serotonergic, noradrenergic or dopaminergic treatments, suggesting that monoamines have a role in these symptoms.
Design/Methods:
Data used in the preparation of this article were obtained from the Parkinson’s Progression Markers Initiative (PPMI) database (https://www.ppmi-info.org/access-data-specimens/download-data). For up-to-date information on the study, visit www.ppmi-info.org. The study included [123I]-FP-CIT SPECT imaging of healthy controls (n=166) and patients with PD at baseline (n=349), 2-year follow-up (n=240), 4-year follow-up (n=140). Depression, anxiety, RBD and cognition were evaluated using GDS-15, STAI, RBDSQ, and MoCA, respectively. The SPECT data were registered to MNI space, and the association between the neuropsychiatric symptoms and monoamine transporter binding was analyzed voxel-by-voxel across brain regions with specific binding.
Results:
In PD patients, there were no significant association between the symptoms and [123I]-FP-CIT specific binding at baseline. Depression was associated with reduced binding in the nucleus accumbens at 2- and 4-year follow-up, and dorsal raphe at 4-year follow-up. Trait anxiety was associated with reduced binding in the raphe nuclei at 4-year follow-up, and RBD in the nucleus accumbens at 2- and 4-year follow-up. These findings were replicated in region-of-interest-based analyses. In contrast, cognitive impairment was not associated with tracer binding. In controls, there were no significant associations between any of these symptoms and tracer binding.
Conclusions:
Our results show that depression, anxiety and RBD are associated with distinct monoaminergic abnormalities. These findings align with the known effects of serotonergic, noradrenergic and dopaminergic treatments and provide new information on the monoaminergic mechanisms underlying neuropsychiatric symptoms in PD.