Serotonergic System Impacts Levodopa Response in Early Parkinson's and Future Risk of Dyskinesia
Bibliographic record
Abstract
ABSTRACT Background The serotonergic system is known to contribute to levodopa‐derived dopamine release in advanced Parkinson's disease. Objective We investigated the role of the serotonergic system in determining response to treatment in early disease and risk for complications concurrently with dopaminergic alterations. Methods Eighteen patients with early and stable Parkinson's disease underwent multitracer positron emission tomography using [11C]dihydrotetrabenazine (vesicular monoamine transporter 2 marker), [11C]methylphenidate (dopamine transporter marker), [11C]‐3‐amino‐4‐(2‐dimethylaminomethylphenylsulfanyl)‐benzonitrile (DASB, serotonin transporter marker), and [11C]raclopride (D2 marker) to investigate relationships between striatal dopaminergic and serotonergic alterations and levodopa‐induced dopamine release, related to motor response to treatment and risk for dyskinesias, using a novel joint pattern analysis. Results The joint pattern analysis revealed correlated spatial patterns conceptually related to abnormal dopamine turnover in the putamen (higher dopamine release associated with dopaminergic and serotonergic denervation); response to treatment significantly inversely correlated with turnover‐related dopamine release (P < 10−5). Patterns identified without inclusion of the DASB data showed no correlation with clinical data, indicating an important contribution from the serotonergic system to a clinically relevant abnormal dopamine release in early disease. Subjects who experienced dyskinesia 3 years after baseline scans showed higher turnover‐related dopamine release compared with subjects who remained stable (P < 0.01). Conclusions Joint analysis of dopaminergic and serotonergic data identified a turnover‐related dopamine release component, strongly related to motor response to levodopa in early disease and contributing to higher risk for dyskinesia. These findings suggest that the contribution of the serotonergic system to dopamine release not only increases the risk for motor complications but also fails to provide sustained therapeutic advantage in early disease. © 2020 International Parkinson and Movement Disorder Society
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".