A1 Refereed original research article in a scientific journal
Monoaminergic Networks of Cognitive and Behavioral Symptoms in Early Parkinson's Disease
Authors: Niemi, Kalle J.; Kaasinen, Valtteri; Weil, Rimona S.; Joutsa, Juho
Publisher: John Wiley & Sons
Publication year: 2026
Journal: Movement Disorders
ISSN: 0885-3185
eISSN: 1531-8257
DOI: https://doi.org/10.1002/mds.70199
Publication's open availability at the time of reporting: Open Access
Publication channel's open availability : Partially Open Access publication channel
Web address : https://doi.org/10.1002/mds.70199
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/509034171
Self-archived copy's licence: CC BY NC ND
Self-archived copy's version: Publisher`s PDF
Background
Parkinson's disease (PD) is associated with several behavioral and cognitive symptoms, the neurobiological background of which is not yet fully understood.
The aim was to investigate the association between monoamine function and four specific nonmotor symptoms in early PD using the Parkinson's Progression Markers Initiative data.
Methods[123I]FP-CIT SPECT imaging data of healthy controls (n = 166) and patients with PD at baseline (n = 349), 2-year (n = 240), and 4-year follow-up (n = 140) were included. Depression, anxiety, rapid eye movement (REM) sleep behavior disorder (RBD) and cognition were evaluated using validated questionnaires. The associations between symptoms and subcortical monoamine transporter binding were analyzed voxel by voxel. Whole brain networks of symptom-specific monoaminergic abnormalities were characterized using a functional connectome (n = 1000) and normative neurotransmitter receptor maps.
ResultsCross-sectionally, depression was associated with reduced ventral striatum (VS) binding at 2- and 4-year and dorsal raphe (DRN) at 4-year follow-up (PFWE < 0.05); trait anxiety was associated with reduced DRN binding at 4-year follow-up (PFWE < 0.05). Longitudinally, lower baseline binding in these regions at baseline predicted more severe future depression and anxiety (PFWE < 0.05). RBD was most strongly linked to reduced VS binding at 2- and 4-year follow-up (nonsignificant after correction, PFWE < 0.1). Each of the symptom-specific clusters was connected to distinct brain networks, corresponding to specific monoamine receptors: serotonin (5HT1F, 5HT2A, 5HT5A) and histamine (H3) for depression; histamine (H1), serotonin (5HT1E, 5HT1F, 5HT2A, 5HT3B), and adrenergic (α1D) for anxiety; and adrenergic (β2) and serotonin (5HT1F, 5HT2C, 5HT5A) receptors for RBD.
ConclusionsThe findings provide novel information about the monoaminergic networks underlying depression, anxiety, and RBD in PD. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society
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Funding information in the publication:
This research was supported by the Finnish Parkinson Foundation, the Finnish Cultural Foundation, the Finnish Society of Nuclear Medicine, Turku University Hospital, TYKS Foundation, and the University of Turku Foundation.
