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

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.

Exploring the underlying mechanisms of drug‐induced impulse control disorders: a pharmacovigilance‐pharmacodynamic study

“…Within the two populations (i.e. dopamine agonist reports and antipsychotic reports, see Supplementary Material-Table S2 and S3), ICD reports were characterized by a significantly higher proportion of men (50.58% vs 47.56% in antipsychotics; 59.90% vs 39.46% in dopamine agonists) and younger age (median[Q1-Q3] = 42 years vs 50 in antipsychotics; 56 [48][49][50][51][52][53][54][55][56][57][58][59][60][61][62][63][64][65] vs 66 in dopamine agonists). Lower proportions of deaths (2.05% vs 12.20% in antipsychotics; 2.42% vs 7.62% in dopamine agonists) and higher of disability (9.60% vs 1.95%; 4.42% vs 2.26%) were also reported.…”

“…The onset of ICDs was earlier for antipsychotics (median [Q1-Q3] = 31 [1-366] days, on 1871 available time to onset data) than for dopamine agonists (214 days, on 662 available time to onset data). Dopamine-agonist related ICDs, compared to antipsychotic-related ICDs, also had higher contribution by men (59.90% vs 50.58%) and older people (56 [48][49][50][51][52][53][54][55][56][57][58][59][60][61][62][63][64][65] vs 42 years old). Finally, the 254 ICD cases recording the use of both dopamine agonists and antipsychotics (Table S4) shared the characteristics of ICDs occurring with dopamine agonists (men 60.00%, age 56 ), but were more similar to ICDs occurring with antipsychotics in the lawyer contribution (15.29%) and the reported disability rate (8.27%), and the reported hospitalization rate (42.13%) was substantially higher than when developing ICDs with dopamine agonists (16.84%) or antipsychotics (32.50%).…”

“…Coherently, in patients with Parkinson, Positron Emission Tomography (PET) approaches have indicated decreased D2R binding and relatively unchanged D1R binding in the ventral striatum in those affected by ICD compared with patients without ICDs. 52 Furthermore, Erga et al identified an increased risk of ICDs in patients with gene polymorphisms in the 5 0 untranslated region (UTR) of the DRD1 gene, which encodes the dopamine receptor D1. 51 Other polymorphisms in DRD1 have been linked to ICDs, neuropsychiatric disease, problem gambling, addiction, and cognitive functioning in non-PD populations.…”

Computational reinforcement learning, reward (and punishment), and dopamine in psychiatric disorders

“…The repetitive engagement in behaviors detrimental to an individual is required for the diagnosis of all addictions—including substance use disorders and behavioral addiction. Also, a loss of control or inhibition often defines the pathology of addictive disorders ( 1 , 41 – 44 ). Work investigating the dopaminergic system and associated RL-models, in addiction, are largely focused on the behavioral reinforcing aspects of addictive stimuli, but what is largely lost in these depictions is the diminished influence of the punishing or aversive stimuli that are also experienced by the patient yet appear to have little influence on behavioral change.…”

Digital health technology for non-motor symptoms in people with Parkinson's disease: Futile or future?

“…Impulse control disorders (ICD) are characterised by the inability to assert self-control in emotions and behaviours, leading to compulsive and/or impulsive actions that harm oneself or others. The pathways involved in ICD have been implicated in rapid eye movement sleep behaviour disorder, constipation, and cognitive impairment [37]. Despite it being an important problem in PD [38], only one study has examined the role of wearables in ICD.…”