Impulse control disorders in advanced Parkinson's disease with dyskinesia: The ALTHEA study

Biundo, Roberta; Weis, Luca; Abbruzzese, Giovanni; Calandra-Buonaura, Giovanna; Cortelli, Pietro; Jori, Maria Cristina; Lopiano, Leonardo; Marconi, Roberto; Matinella, Angela; Morgante, Francesca; Nicoletti, Alessandra; Tamburini, Tiziano; Tinazzi, Michèle; Zappia, Mario; Vorovenci, Ruxandra Julia; Antonini, Angelo

doi:10.1002/mds.27181

Cited by 64 publications

(48 citation statements)

References 54 publications

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“…Interestingly, animals exposed to an LR schedule were found to be more dyskinetic than animals under an HR regimen. This effect is consistent with clinical observations that in patients with severe dyskinesia, a significantly higher frequency of impulse control disorders is observed . Chronic drug treatment may therefore be addressed for the increasing levels of chocolate intake in 6‐OHDA rats receiving chocolate.…”

Section: Discussionsupporting

confidence: 88%

Dopamine drives binge‐like consumption of a palatable food in experimental Parkinsonism

et al. 2019

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A BS TRACT: Background: Prolonged dopaminergic replacement therapy in PD results in pulsatile dopamine receptors stimulation in both dorsal and ventral striatum causing wearing off, motor fluctuations, and nonmotor side effects such as behavioral addictions. Among impulse control disorders, binge eating can be easily modeled in laboratory animals. Objectives: We hypothesize that manipulation of dopamine levels in a 6-hydroxydopamine-lesioned rats, as a model of PD characterized by a different extent of dopamine denervation between dorsal and ventral striatum, would influence both synaptic plasticity of the nucleus accumbens and binge-like eating behavior. Methods: Food preference, food intake, and weight gain were monitored in sham-operated and unilaterally lesioned rats, subjected to a modified version of Corwin's limited access protocol, modelling binge eating disorder. Electrophysiological properties and long-term potentiation of GABAergic spiny projection neurons of the nucleus accumbens core were studied through ex vivo intracellular and patch-clamp recordings from corticostriatal slices of naïve and L-dopa-treated rats. Results: Sham-operated animals with intact nucleus accumbens core plasticity reliably developed food-addiction-like behavior when exposed to intermittent access to a highly palatable food. In contrast, parkinsonian rats were unresponsive to such restriction regimens, and also plasticity was lost in ventral spiny neurons. Chronic L-dopa reestablished long-term potentiation and compulsive eating, but with a different temporal dynamic that follows that of drug administration. Conclusions: Our data indicate that endogenous and exogenous dopamine drive binge-like consumption of a palatable food in healthy and parkinsonian rats with distinct temporal dynamics, providing new insights into the complexity of L-dopa effects on the mesolimbic dopaminergic system.

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Section: Discussionsupporting

confidence: 88%

Dopamine drives binge‐like consumption of a palatable food in experimental Parkinsonism

et al. 2019

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“…Interestingly, patients with ICDs presented with a higher familial history of addictive behaviors (pathological gambling, alcohol abuse), suggesting an important genetic component in this population. In addition, PD patients with ICDs and related behaviors presented more severe nonmotor complications (UPDRS I) and motor complications (UPDRS IV), in accordance with recent studies showing an association of ICDs with dyskinesia and sleep disorders, suggesting common pathogenic mechanisms responsible for the development of severe versions of the disease and emergence of ICDs …”

Section: Discussionmentioning

confidence: 99%

Suggestive association between OPRM1 and impulse control disorders in Parkinson's disease

et al. 2018

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Background Impulse control disorders are frequently associated with dopaminergic therapy in Parkinson's disease. Genetic studies have suggested a high heritability of impulse control disorders in the general population and in PD. The aim of this study was to identify candidate gene variants associated with impulse control disorders and related behaviors in PD. Methods We performed a multicenter case‐control study in PD patients with (cases) or without impulse control disorders and related behaviors despite significant dopamine agonist exposure of >300 mg levodopa‐equivalent daily dose during 12 months (controls). Behavioral disorders were assessed using the Ardouin scale. We investigated 50 variants in 24 candidate genes by a multivariate logistic regression analysis adjusted for sex and age at PD onset. Results The analysis was performed on 172 cases and 132 controls. Cases were younger (60 ± 8 vs 63 ± 8 years; P < 0.001) and had a higher family history of pathological gambling (12% vs 5%, P = 0.03). No variant was significantly associated with impulse control disorders or related behaviors after correction for multiple testing, although the 2 top variants were close to significant (OPRM1 rs179991, OR, 0.49; 95%CI, 0.32‐0.76; P = 0.0013; Bonferroni adjusted P = 0.065; DAT1 40‐base pair variable number tandem repeat, OR, 1.82; 95%CI, 1.24‐2.68; P = 0.0021; Bonferroni adjusted P = 0.105). Conclusions Our results are suggestive of a novel association of the opioid receptor gene OPRM1 with impulse control disorders and related behaviors in PD and confirm a previous association with DAT1. Although replication in independent studies is needed, our results bring potential new insights to the understanding of molecular mechanisms of impulse control disorders. © 2018 International Parkinson and Movement Disorder Society

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“…In addition, considering the compulsive behavior of ICBs and the involuntary movements of LIDs, it could be postulated that these phenomena share common mechanisms and neural pathways . According to this theory, an increased frequency of clinically significant ICBs in patients with severe dyskinesia have been observed . Again, LIDs and ICBs could both be considered abnormal behaviors induced by excessive dopaminergic stimulation, in predisposed subjects in the motor or limbic areas of the striatum, leading to functional changes in different areas of the basal ganglia and cortex resembling the motor or associative/limbic circuits.…”

Section: Discussionmentioning

confidence: 99%

MRI of Motor and Nonmotor Therapy‐Induced Complications in Parkinson's Disease

2020

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Levodopa therapy remains the most effective drug for the treatment of Parkinson's disease, and it is associated with the greatest improvement in motor function as assessed by the Unified Parkinson's Disease Rating Scale. Dopamine agonists have also proven their efficacy as monotherapy in early Parkinson's disease but also as adjunct therapy. However, the chronic use of dopaminergic therapy is associated with disabling motor and nonmotor side effects and complications, among which levodopa‐induced dyskinesias and impulse control behaviors are the most common. The underlying mechanisms of these disorders are not fully understood. In the last decade, classic neuroimaging methods and more sophisticated techniques, such as analysis of gray‐matter structural imaging and functional magnetic resonance imaging, have given access to anatomical and functional abnormalities, respectively, in the brain. This review presents an overview of structural and functional brain changes associated with motor and nonmotor therapy‐induced complications in Parkinson's disease. Magnetic resonance imaging may offer structural and/or functional neuroimaging biomarkers that could be used as predictive signs of development, maintenance, and progression of these complications. Neurophysiological tools, such as theta burst stimulation and transcranial magnetic stimulation, might help us to integrate neuroimaging findings and clinical features and could be used as therapeutic options, translating neuroimaging data into clinical practice. © 2020 International Parkinson and Movement Disorder Society

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Impulse control disorders in advanced Parkinson's disease with dyskinesia: The ALTHEA study

Cited by 64 publications

References 54 publications

Dopamine drives binge‐like consumption of a palatable food in experimental Parkinsonism

Dopamine drives binge‐like consumption of a palatable food in experimental Parkinsonism

Suggestive association between OPRM1 and impulse control disorders in Parkinson's disease

MRI of Motor and Nonmotor Therapy‐Induced Complications in Parkinson's Disease

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