The neurobiology of impulse control disorders in Parkinson’s disease: from neurotransmitters to neural networks

Abstract

Impulse control disorders (ICD) are common neuropsychiatric disorders that can arise in Parkinson’s disease (PD) patients after commencing dopamine replacement therapy. Approximately 15% of all patients develop these disorders and many more exhibit subclinical symptoms of impulsivity. ICD is thought to develop due to an interaction between the use of dopaminergic medication and an as yet unknown neurobiological vulnerability that either pre-existed before PD onset (possibly genetic) or is associated with neural alterations due to the PD pathology. This review discusses genes, neurotransmitters and neural networks that have been implicated in the pathophysiology of ICD in PD. Although dopamine and the related reward system have been the main focus of research, recently, studies have started to look beyond those systems to find new clues to the neurobiological underpinnings of ICD and come up with possible new targets for treatment. Studies on the whole-brain connectome to investigate the global alterations due to ICD development are currently lacking. In addition, there is a dire need for longitudinal studies that are able to disentangle the contributions of individual (genetic) traits and secondary effects of the PD pathology and chronic dopamine replacement therapy to the development of ICD in PD.

Epidemiology and Management Challenges in Prolactinomas

“…Impulse control disorders seen with dopamine agonists include pathological gambling, compulsive shopping, hypersexuality, binge-eating, or the repetitive performance of purposeless mechanical activities (known as "punding") [72]. The etiology of this complex disorder is thought to be related to a hyperdopaminergic state in specific regions of the brain [73]. In Parkinson's disease patients these impulse control disorders occur in >13% of patients [74].…”

Pharmacological insights into impulsive‐compulsive spectrum disorders associated with dopaminergic therapy

“…Dopamine agonist therapy for neurological disorders provides excellent motor benefits, but it is associated with the emergence of disorders related to impulse control and compulsiveness in some treated patients (Grall-Bronnec et al, 2018). There is considerable debate regarding what features of dopamine transmission are responsible for the various behaviors, and what are the roles of therapy, pathology, or neuroplasticity in the behavioral manifestations (Lawrence et al, 2003;Napier et al, 2015;Brusa et al, 2016;Evens et al, 2016;Houeto et al, 2016;Morgante et al, 2016;Maloney et al, 2017;Vriend, 2018). Adding to the conundrum are reports of these disorders emerging during therapy with dopamine receptor partial agonists used to treat (e.g.)…”

Special issue “Parkinson’s disease”

“…In other words, some subsets of PD patients would never develop the ENS Lewy pathology in the ENS reported by previous researchers (Wakabayashi et al 1988;Beach et al 2010;Stokholm et al 2016). Vriend (2018) provides insights into the neurobiological aspects of impulse control disorders (ICD), e.g., compulsive shopping or internet use, binge eating, hypersexuality, pathological gambling, which some PD patients develop within the context of dopamine replacement therapy (Wu et al 2014;Weintraub et al 2010;Weintraub et al 2015). In the first part of his review, Vriend summarizes the contributions of dopamine to ICD together with the dopaminergic vulnerability to ICD development.…”