Trait Impulsivity and Anhedonia: Two Gateways for the Development of Impulse Control Disorders in Parkinson’s Disease?

Abstract

Apathy and impulsivity are two major comorbid syndromes of Parkinson’s disease (PD) that may represent two extremes of a behavioral spectrum modulated by dopamine-dependent processes. PD is characterized by a progressive loss of dopaminergic neurons in the substantia nigra pars compacta to which are attributed the cardinal motor symptoms of the disorder. Dopamine replacement therapy (DRT), used widely to treat these motor symptoms, is often associated with deficits in hedonic processing and motivation, including apathy and depression, as well as impulse control disorders (ICDs). ICDs comprise pathological gambling, hypersexuality, compulsive shopping, binge eating, compulsive overuse of dopaminergic medication, and punding. More frequently observed in males with early onset PD, ICDs are associated not only with comorbid affective symptoms, such as depression and anxiety, but also with behavioral traits, such as novelty seeking and impulsivity, as well as with personal or familial history of alcohol use. This constellation of associated risk factors highlights the importance of inter-individual differences in the vulnerability to develop comorbid psychiatric disorders in PD patients. Additionally, withdrawal from DRT in patients with ICDs frequently unmasks a severe apathetic state, suggesting that apathy and ICDs may be caused by overlapping neurobiological mechanisms within the cortico-striato-thalamo-cortical networks. We suggest that altered hedonic and impulse control processes represent distinct prodromal substrates for the development of these psychiatric symptoms, the etiopathogenic mechanisms of which remain unknown. Specifically, we argue that deficits in hedonic and motivational states and impulse control are mediated by overlapping, yet dissociable, neural mechanisms that differentially interact with DRT to promote the emergence of ICDs in vulnerable individuals. Thus, we provide a novel heuristic framework for basic and clinical research to better define and treat comorbid ICDs in PD.

Genes associated with anhedonia: a new analysis in a large clinical trial (GENDEP)

“…Specifically, anhedonia in our study was positively correlated with PD (rg = 0.8). In fact, anhedonia independent of clinical diagnosis and PD are both dopamine-dependent processes and anhedonia is one of the most commonly observed non-motor symptoms in PD 82 , 83 . Moreover, anhedonia was negatively correlated with nucleus accumbens gray matter volume (rg = −0.6).…”

Dopamine and reward hypersensitivity in Parkinson’s disease with impulse control disorder

“…Indeed, healthy controls have been shown to have levels of ICB equivalent to newly diagnosed Parkinson’s disease patients ( Antonini et al , 2011 ; Weintraub et al , 2013 ). Rather, ICDs in Parkinson’s disease are considered to develop in response to dopamine agonist treatment and interact with underlying Parkinson’s disease pathophysiology and possibly personality traits to manifest as particular behavioural phenotypes ( Weintraub et al , 2013 ; Garcia-Ruiz et al , 2014 ; Sharma et al , 2015 ; Houeto et al , 2016 ; Dawson et al , 2018 ; Baig et al , 2019 ). In particular, ICDs have been associated with the use of non-ergolinic oral dopamine agonists, such as rasagiline, ropinirole and pramipexole ( Garcia-Ruiz et al , 2014 ; Weintraub et al , 2015 ), but also with the use of ergoline-derivatives such as cabergoline ( Weintraub et al , 2010 ), although no straightforward dose-dependent relationship, across individuals, has yet been demonstrated ( Ambermoon et al , 2011 ; Corvol et al , 2018 ; Dawson et al , 2018 ).…”

Impulse-Control Disorders in Parkinson’s Disease: A Meta-Analysis and Review of Case–Control Studies

“…Impulse control disorders (ICDs) are a collective term for non-motor symptoms that include pathological gambling, compulsive shopping, hypersexuality, and binge eating ( 1 ). In addition, behavioral disorders such as hobbyism (including pathological internet use), punding, and walkabout have been reported in patients with Parkinson’s disease (PD) ( 2 – 4 ).…”

“…Although several narrative reviews on ICDs related to PD have been published ( 1 , 35 , 36 ), a quantitative meta-analysis that summarizes the existing research could extend earlier reviews by providing overall prevalence estimates (precision estimates) as well as identifying significant moderator variables. Against this backdrop, we conducted a meta-analysis of ICDs in PD aiming to determine the overall prevalence of different ICDs in PD patients in comparison with healthy controls across case–control studies.…”