Neurobiology and clinical features of impulse control failure in Parkinson\u2019s disease

Matthieu Béreau,Thomas F Münte,Norbert Brüggemann,Paul Krack

doi:10.1186/s42466-019-0013-5

Abstract

Impulse control disorders (ICDs) and other impulsive-compulsive related behaviours are frequent and still under recognized non-motor complications of Parkinson’s disease (PD). They result from sensitization of the mesocorticolimbic pathway that arose in predisposed PD patients concomitantly with spreading of PD pathology, non-physiological dopaminergic and pulsatile administration of dopamine replacement therapy (DRT). Neuropsychiatric fluctuations (NPF) reflect the psychotropic effects of dopaminergic drugs and play a crucial role in the emergence of ICDs and behavioral addictions. Dopamine agonists (DA) which selectively target D2 and D3 receptors mostly expressed within the mesocorticolimbic pathway, are the main risk factor to develop ICDs. Neuroimaging studies suggest that dopamine agonists lead to a blunted response of the brain’s reward system both during reward delivery and anticipation. Genetic predispositions are crucial for the responsiveness of the mesolimbic system and the development of ICDs with several genes having been identified. Early screening for neuropsychiatric fluctuations, reduction of DA, fractionating levodopa dosage, education of patients and their relatives, are the key strategies for diagnosis and management of ICDs and related disorders.

Highlights

Motor signs namely bradykinesia, rigidity and tremor are still considered as the core feature of diagnostic criteria for Parkinson disease (PD) [71], increasing recognition has been given over time to non-motor manifestations of PD including cognitive, autonomic, and neuropsychiatric signs [99]
Neuropsychiatric signs encompass neuropsychiatric fluctuations (NPF), Impulse control disorders (ICDs) and related disorders, and psychosis that are frequently observed along the progression of PD pathology and the concurrent pulsatile administration
Behavioral addictions / ICDs present a major problem in the clinical management of PD

Summary

Introduction

Motor signs namely bradykinesia, rigidity and tremor are still considered as the core feature of diagnostic criteria for Parkinson disease (PD) [71], increasing recognition has been given over time to non-motor manifestations of PD including cognitive, autonomic, and neuropsychiatric signs [99]. Neuropsychiatric signs refer first of all to anxiety, apathy and depression that are frequently encountered in de novo drug-naïve PD patients [54] and reverted when dopamine replacement therapy (DRT) is introduced [66, 81]. Neuropsychiatric signs encompass neuropsychiatric fluctuations (NPF), Impulse control disorders (ICDs) and related disorders, and psychosis that are frequently observed along the progression of PD pathology and the concurrent pulsatile administration. Behavioural disorders in PD have been conceptualized as a hypodopaminergic behavioural syndrome where apathy predominates, hyperdopaminergic behavioural syndrome which includes ICDs and other behavioural addictions, and non-motor fluctuations [2, 75] that together, define two opposite sides of one behavioural spectrum [81]. ICDs and related disorders are underpinned by one common pathophysiological mechanism that consists in hypersensitization of reward circuits and heightened ventral striatal dopamine release in response to reward-related cues [52]. From a clinical perspective, pathological gambling has been removed from ICDs in DSM-IV

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Conclusion