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.
Highlights
Specialty section: This article was submitted to Neurodegeneration, a section of the journal Frontiers in Psychiatry
We capitalize on the wealth of literature on the neurobiological mechanisms of impulsivity and anhedonia-related behaviors in Parkinson’s disease (PD) to suggest that impulse control and hedonic/ motivational deficits may represent distinct prodromic gates for the development of impulse control disorders (ICDs), through compulsive enhancement seeking and self-medication failure, respectively
In light of the recent evidence that a reduced striatal dopamine transporter availability predates the development of Dopamine replacement therapy (DRT)-related ICDs [163], this study suggests that the striatal neurobiological underpinnings of apathy/anhedonia may represent a risk factor for the development of DRT-related ICDs
Summary
Idiopathic Parkinson’s disease (PD) is a neurodegenerative disorder, resulting mainly from the loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc) and characterized by tremor, rigidity, and bradykinesia [1]. We capitalize on the wealth of literature on the neurobiological mechanisms of impulsivity and anhedonia-related behaviors in PD to suggest that impulse control and hedonic/ motivational deficits may represent distinct prodromic gates for the development of ICDs, through compulsive enhancement seeking and self-medication failure, respectively. Based on these hypotheses, we propose a novel heuristic framework to implement relevant preclinical studies and improve the management of comorbid psychiatric symptoms in PD
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