Impulse Control Disorders in Parkinson's Disease: From Bench to Bedside.

Andrea Augustine,Catharine A Winstanley,Vaishnav Krishnan

doi:10.3389/fnins.2021.654238

Abstract

Parkinson’s disease (PD) is a neurodegenerative disorder that is characterized by symptoms that impact both motor and non-motor domains. Outside of motor impairments, PD patients are at risk for impulse control disorders (ICDs), which include excessively disabling impulsive and compulsive behaviors. ICD symptoms in PD (PD + ICD) can be broadly conceptualized as a synergistic interaction between dopamine agonist therapy and the many molecular and circuit-level changes intrinsic to PD. Aside from discontinuing dopamine agonist treatment, there remains a lack of consensus on how to best address ICD symptoms in PD. In this review, we explore recent advances in the molecular and neuroanatomical mechanisms underlying ICD symptoms in PD by summarizing a rapidly accumulating body of clinical and preclinical studies, with a special focus on the utility of rodent models in gaining new insights into the neurochemical basis of PD + ICD. We also discuss the relevance of these findings to the broader problem of impulsive and compulsive behaviors that impact a range of neuropsychiatric syndromes.

Highlights

Parkinson’s disease (PD) affects more than 10 million people worldwide (Dorsey et al, 2018; Rocca, 2018)
Positron emission tomography (PET) approaches have indicated decreased D2-like receptors (D2R) binding (Steeves et al, 2009; Stark et al, 2018) and relatively unchanged D1-like receptors (D1R) binding in the ventral striatum in PD + impulse control disorders (ICDs) (Payer et al, 2015) compared with PD patients without ICDs (PD-ICD). These findings suggest that ICD symptoms may reflect dopamine agonists (DAAs)-mediated D2R overstimulation preventing punishment learning wherein adverse consequences of actions are ignored when making decisions, while the effects of D1R-mediated direct pathway and positive reinforcement learning are intact
In rodents, decreased risk-taking and losschasing was reported following lesioning to the subthalamic nucleus (STN), possibly pinpointing this region as a target for deep brain stimulation (DBS) and other treatments for PD + ICD (Breysse et al, 2020)

Summary

Introduction

Parkinson’s disease (PD) affects more than 10 million people worldwide (Dorsey et al, 2018; Rocca, 2018). Recent research has suggested a difference in the nature of ICRBs among these populations, whereby delay discounting (with preference for smaller and more immediate rewards over larger but more delayed rewards) and deficits in reflection impulsivity (ability to collect sufficient information prior to decision-making) better predict ICDs in the PD and general populations, respectively (Izzo et al, 2020). FMRI studies in which medicated subjects performed tasks to measure impulsivity have observed lower activation in the prefrontal cortex (PFC) and striatum during these tasks in PD + ICD (Filip et al, 2018).

Results

Conclusion