Parkinson's disease under dopamine replacement therapy as a human framework for studying addiction‐relevant mechanisms
10 affiliations
- 1Department of Neurology Geneva University Hospital Geneva Switzerland
- 2Faculty of Medicine University of Geneva, Rue Michel‐Servet 1 Geneva Switzerland
- 3Rehabilitation Neural Engineering Laboratories University of Pittsburgh Pittsburgh Pennsylvania USA
- 4Physical Medicine and Rehabilitation University of Pittsburgh Pittsburgh Pennsylvania USA
- 5Bioengineering University of Pittsburgh Pittsburgh Pennsylvania USA
- 6Neuroscience of Emotion and Affective Lab University of Geneva Geneva Switzerland
- 7Addictology Division, Mental Health and Psychiatry Department Geneva University Hospital Geneva Switzerland
- 8Department of Basic Neurosciences, Faculty of Medicine University of Geneva Geneva Switzerland
- 9Synapsy Center for Mental Health Research University of Geneva Geneva Switzerland
- 10Department of Neurology Inselspital, University Hospital Bern, University of Bern Bern Switzerland
Abstract
Addiction is a chronic relapsing condition characterized by compulsive reward seeking and impaired behavioral control, associated with major individual and societal burden. Mechanistic investigation in humans remains constrained by ethical limitations, uncontrolled exposure histories, and ecological confounds. Parkinson's disease treated with dopamine replacement therapy provides a human framework for investigating addiction‐relevant mechanisms under controlled dopaminergic modulation. We performed a narrative synthesis of clinical, neuropsychological, pharmacological, neuroimaging, and electrophysiological evidence linking impulse control disorders and dopamine dysregulation syndrome in Parkinson's disease to dimensional and circuit‐based models of addiction. We examined phenotypic and neurobiological convergences, experimental opportunities, and translational relevance while outlining its boundary conditions. A subset of Parkinson's disease patients exposed to dopamine replacement treatment develops impulse control disorders and dopamine dysregulation syndrome. Impulse control disorders comprise heterogeneous behavioral phenotypes that share selected dimensions with behavioral addictions, whereas dopamine dysregulation syndrome most closely approximates pharmacological substance use disorders. These phenotypes share selected addiction‐related dimensions, including craving, impaired control, compulsive reward‐seeking, and persistence despite harm, while showing partial clinical and neurobiological convergence with behavioral addictions and substance use disorders. Parkinson's disease patients with neuropsychiatric fluctuations may represent a sensitized vulnerability state in which dopaminergic modulation dynamically influences reward processing, motivation, and compulsive behaviors. Parkinson's disease under dopamine replacement therapy enables within‐subject dopaminergic manipulation, longitudinal observation, prospective assessment of vulnerability traits, multimodal neurobiological investigation, and reduced environmental confounding. It therefore provides a unique human window for investigating addiction‐relevant mechanisms under controlled dopaminergic modulation, complementing animal models while remaining constrained by disease‐specific boundary conditions.
Related
- Dopamine replacement therapy modulates DDC, prolactin and AOC3 levels in Parkinson’s disease
- Psychiatric and Behavioral Adverse Event Reporting Patterns Among Dopamine Agonists in Parkinson’s Disease Using the Food and Drug Administration Adverse Event Reporting System
- Dopamine Metabolism as a Chemically Constrained Network: Structural Regulation, Redox Liability and Dopaminergic Vulnerability in Parkinson’s Disease
- Dopamine amplifies subthalamic long-latency responses to cortical stimulation in patients with Parkinson's disease.
- The effects of use of medications on striatal dopamine transporter binding assessed by [123I]I-FP-CIT SPECT in patients with Parkinson’s disease from the PPMI cohort
BibTeX
@article{fleury2026parkinsons,
title = {{Parkinson's disease under dopamine replacement therapy as a human framework for studying addiction‐relevant mechanisms}},
author = {Vanessa Fleury and Elvira Pirondini and Damien Benis and Tiffany Corbet and Gabriel Thorens and Christian Lüscher and Paul Krack},
journal = {Psychiatry and Clinical Neurosciences},
year = {2026},
month = aug,
doi = {10.1111/pcn.70118},
url = {https://doi.org/10.1111/pcn.70118},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Parkinson's disease under dopamine replacement therapy as a human framework for studying addiction‐relevant mechanisms
AU - Vanessa Fleury
AU - Elvira Pirondini
AU - Damien Benis
AU - Tiffany Corbet
AU - Gabriel Thorens
AU - Christian Lüscher
AU - Paul Krack
PY - 2026
DA - 2026/08/11
JO - Psychiatry and Clinical Neurosciences
DO - 10.1111/pcn.70118
UR - https://doi.org/10.1111/pcn.70118
AB - Addiction is a chronic relapsing condition characterized by compulsive reward seeking and impaired behavioral control, associated with major individual and societal burden. Mechanistic investigation in humans remains constrained by ethical limitations, uncontrolled exposure histories, and ecological confounds. Parkinson's disease treated with dopamine replacement therapy provides a human framework for investigating addiction‐relevant mechanisms under controlled dopaminergic modulation. We performed a narrative synthesis of clinical, neuropsychological, pharmacological, neuroimaging, and electrophysiological evidence linking impulse control disorders and dopamine dysregulation syndrome in Parkinson's disease to dimensional and circuit‐based models of addiction. We examined phenotypic and neurobiological convergences, experimental opportunities, and translational relevance while outlining its boundary conditions. A subset of Parkinson's disease patients exposed to dopamine replacement treatment develops impulse control disorders and dopamine dysregulation syndrome. Impulse control disorders comprise heterogeneous behavioral phenotypes that share selected dimensions with behavioral addictions, whereas dopamine dysregulation syndrome most closely approximates pharmacological substance use disorders. These phenotypes share selected addiction‐related dimensions, including craving, impaired control, compulsive reward‐seeking, and persistence despite harm, while showing partial clinical and neurobiological convergence with behavioral addictions and substance use disorders. Parkinson's disease patients with neuropsychiatric fluctuations may represent a sensitized vulnerability state in which dopaminergic modulation dynamically influences reward processing, motivation, and compulsive behaviors. Parkinson's disease under dopamine replacement therapy enables within‐subject dopaminergic manipulation, longitudinal observation, prospective assessment of vulnerability traits, multimodal neurobiological investigation, and reduced environmental confounding. It therefore provides a unique human window for investigating addiction‐relevant mechanisms under controlled dopaminergic modulation, complementing animal models while remaining constrained by disease‐specific boundary conditions.
SN - 1323-1316
SN - 1440-1819
ER -