Impulse Control Disorders in Parkinson's Disease: Epidemiology, Pathogenesis and Therapeutic Strategies.
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ABSTRACT:
SUBMITTER: Zhang JF
PROVIDER: S-EPMC7900512 | biostudies-literature | 2021
REPOSITORIES: biostudies-literature
Publications
Impulse Control Disorders in Parkinson's Disease: Epidemiology, Pathogenesis and Therapeutic Strategies.
Zhang Jun-Fang JF Wang Xi-Xi XX Feng Ya Y Fekete Robert R Jankovic Joseph J Wu Yun-Cheng YC
Frontiers in psychiatry 20210209
Impulse control disorders (ICDs) in Parkinson's disease (PD) are aberrant behavior such as pathological gambling, hypersexuality, binge eating, and compulsive buying, which typically occur as a result of dopaminergic therapy. Numerous studies have focused on the broad spectrum of ICDs-related behaviors and their tremendous impact on patients and their family members. Recent advances have improved our understanding of ICDs. In this review, we discuss the epidemiology, pathogenesis and treatment o ...[more]
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Project description:Impulse control and related disorders (ICDs-RD) encompasses a heterogeneous group of disorders that involve pleasurable behaviors performed repetitively, excessively, and compulsively. The key common symptom in all these disorders is the failure to resist an impulse or temptation to control an act or specific behavior, which is ultimately harmful to oneself or others and interferes in major areas of life. The major symptoms of ICDs include pathological gambling (PG), hypersexualtiy (HS), compulsive buying/shopping (CB) and binge eating (BE) functioning. ICDs and ICDs-RD have been included in the behavioral spectrum of non-motor symptoms in Parkinson's disease (PD) leading, in some cases, to serious financial, legal and psychosocial devastating consequences. Herein we present the prevalence of ICDs, the risk factors, its pathophysiological mechanisms, the link with agonist dopaminergic therapies and therapeutic managements.
| S-EPMC6481351 | biostudies-literature
Project description:Impulse control disorders (ICD) are commonly associated with dopamine replacement therapy (DRT) in patients with Parkinson's disease (PD). Our aims were to estimate ICD heritability and to predict ICD by a candidate genetic multivariable panel in patients with PD.Data from de novo patients with PD, drug-naïve and free of ICD behaviour at baseline, were obtained from the Parkinson's Progression Markers Initiative cohort. Incident ICD behaviour was defined as positive score on the Questionnaire for Impulsive-Compulsive Disorders in PD. ICD heritability was estimated by restricted maximum likelihood analysis on whole exome sequencing data. 13 candidate variants were selected from the DRD2, DRD3, DAT1, COMT, DDC, GRIN2B, ADRA2C, SERT, TPH2, HTR2A, OPRK1 and OPRM1 genes. ICD prediction was evaluated by the area under the curve (AUC) of receiver operating characteristic (ROC) curves.Among 276 patients with PD included in the analysis, 86% started DRT, 40% were on dopamine agonists (DA), 19% reported incident ICD behaviour during follow-up. We found heritability of this symptom to be 57%. Adding genotypes from the 13 candidate variants significantly increased ICD predictability (AUC=76%, 95% CI (70% to 83%)) compared to prediction based on clinical variables only (AUC=65%, 95% CI (58% to 73%), p=0.002). The clinical-genetic prediction model reached highest accuracy in patients initiating DA therapy (AUC=87%, 95% CI (80% to 93%)). OPRK1, HTR2A and DDC genotypes were the strongest genetic predictive factors.Our results show that adding a candidate genetic panel increases ICD predictability, suggesting potential for developing clinical-genetic models to identify patients with PD at increased risk of ICD development and guide DRT management.
| S-EPMC5098340 | biostudies-literature
Project description:Introduction:Impulse control disorders (ICDs) are frequent non-motor symptoms in Parkinson's disease (PD), with potential negative effects on the quality of life and social functioning. ICDs are closely associated with dopaminergic therapy, and genetic polymorphisms in several neurotransmitter pathways may increase the risk of addictive behaviors in PD. However, clinical differentiation between patients at risk and patients without risk of ICDs is still troublesome. The aim of this study was to investigate if genetic polymorphisms across several neurotransmitter pathways were associated with ICD status in patients with PD. Methods:Whole-exome sequencing data were available for 119 eligible PD patients from the Norwegian ParkWest study. All participants underwent comprehensive neurological, neuropsychiatric, and neuropsychological assessments. ICDs were assessed using the self-report short form version of the Questionnaire for Impulsive-Compulsive Disorders in PD. Single-nucleotide polymorphisms (SNPs) from 17 genes were subjected to regression with elastic net penalization to identify candidate variants associated with ICDs. The area under the curve of receiver-operating characteristic curves was used to evaluate the level of ICD prediction. Results:Among the 119 patients with PD included in the analysis, 29% met the criteria for ICD and 63% were using dopamine agonists (DAs). Eleven SNPs were associated with ICDs, and the four SNPs with the most robust performance significantly increased ICD predictability (AUC?=?0.81, 95% CI 0.73-0.90) compared to clinical data alone (DA use and age; AUC?=?0.65, 95% CI 0.59-0.78). The strongest predictive factors were rs5326 in DRD1, which was associated with increased odds of ICDs, and rs702764 in OPRK1, which was associated with decreased odds of ICDs. Conclusion:Using an advanced statistical approach, we identified SNPs in nine genes, including a novel polymorphism in DRD1, with potential application for the identification of PD patients at risk for ICDs.
| S-EPMC5835501 | biostudies-literature
Project description:Impulse control disorder is a prevalent side-effect of Parkinson's disease (PD) medication, with a strong negative impact on the quality of life of those affected. Although impulsivity has classically been associated with response inhibition deficits, previous evidence from PD patients with impulse control disorder (ICD) has not revealed behavioral dysfunction in response inhibition. In this study, 18 PD patients with ICD, 17 PD patients without this complication, and 15 healthy controls performed a version of the conditional Stop Signal Task during functional magnetic resonance imaging. Whole-brain contrasts, regions of interest, and functional connectivity analyses were conducted. Our aim was to investigate the neural underpinnings of two aspects of response inhibition: proactive inhibition, inhibition that has been prepared beforehand, and restrained inhibition, inhibition of an invalid inhibitory tendency. We observed that, in respect to the other two groups, PD patients with ICD exhibited hyperactivation of the stopping network bilaterally while performing proactive inhibition. When engaged in restrained inhibition, they showed hyperactivation of the left inferior frontal gyrus, an area linked to action monitoring. Restrained inhibition also resulted in changes to the functional co-activation between inhibitory regions and left inferior parietal cortex and right supramarginal gyrus. Our findings indicate that PD patients with ICD completed the inhibition task correctly, showing altered engagement of inhibitory and attentional areas. During proactive inhibition they showed bilateral hyperactivation of two inhibitory regions, while during restrained inhibition they showed additional involvement of attentional areas responsible for alerting and orienting.
| S-EPMC8449263 | biostudies-literature
Project description:Impulse control disorders (ICDs) in Parkinson's disease (PD) are considered dopaminergic treatment side effects. Cognitive and affective factors may increase the risk of ICD in PD. The aim is to investigate risky decision-making and associated cognitive processes in PD patients with ICDs within a four-stage conceptual framework. Relationship between ICDs and affective factors was explored. Thirteen PD patients with ICD (ICD+), 12 PD patients without ICD (ICD-), and 17 healthy controls were recruited. Overall risky decision-making and negative feedback effect were examined with the Balloon Analogue Risk Task (BART). A cognitive battery dissected decision-making processes according to the four-stage conceptual framework. Affective and motivational factors were measured. ANOVA showed no effect of group on overall risky decision-making. However, there was a group × feedback interaction [F (2, 39) = 3.31, p = 0.047]. ICD+, unlike ICD- and healthy controls, failed to reduce risky behaviour following negative feedback. A main effect of group was found for anxiety and depression [F(2, 38) = 8.31, p = 0.001], with higher symptoms in ICD+ vs. healthy controls. Groups did not differ in cognitive outcomes or affective and motivational metrics. ICD+ may show relatively preserved cognitive function, but reduced sensitivity to negative feedback during risky decision-making and higher symptoms of depression and anxiety.
| S-EPMC5775350 | biostudies-other
Project description:Although several case-control studies on the prevalence of Impulse-Control Disorders (ICDs) in Parkinson's Disease (PD) have been conducted, no meta-analytic study on this topic has previously been published. Thus, knowledge about the overall prevalence rate of ICD in PD and factors that might moderate this relationship is lacking.Prevalence studies of ICDs in PD were identified by computer searches in the MEDLINE, PsycINFO, and Web of Science databases, covering the period from January 2000 to February 2017. Data for N?=?4,539, consisting of 2,371 PD patients and 2,168 healthy controls, representing 14 case-control studies were included. Estimation of the odds ratio (OR) of ICDs in PD compared to healthy controls was conducted using random-effects models. Mixed-effects models were applied in the moderator analysis of heterogeneity. Publication bias was estimated using a contour-enhanced funnel plot, the Rüker's test, and fail-safe N test for estimating the number of potential missing studies.Overall, the results showed significantly higher ratios for several ICDs in PD compared to healthy controls with the estimated overall ORs ranging between 2.07, 95% CI [1.26, 3.48], for having any ICDs, and 4.26, 95% CI [2.17, 8.36], for hypersexuality. However, the random-effects results for shopping were non-significant, though the fixed-effects model was significant (OR?=?1.66, 95%CI [1.21, 2.27]). The testing of potential moderator variables of heterogeneity identified the following two variables that were both associated with increased risk: being medically treated for PD and disease duration. The results must be interpreted with some caution due to possible small-studies effect or publication bias.Individuals with PD seem to have a significantly greater risk of suffering from ICDs compared to healthy controls. Gambling, hypersexuality, eating, punding, and hobbying are all ICDs significantly associated with PDs being medically treated for PD.
| S-EPMC5972311 | biostudies-other
Project description:Given that impulse control disorders (ICDs) have been identified among a considerable minority of Parkinson's disease (PD) patients, these conditions have gained increased clinical and research attention in the past decade. Dopamine-replacement therapies, taken to ameliorate PD symptoms, have been associated with ICDs in PD. Unfortunately, there are relatively sparse empirical data regarding how best to address ICDs in PD patients. Conversely, progress has been made in understanding the clinical, neurobiological and cognitive correlates of ICDs in PD. Some of these findings may inform possible courses of action for care providers working with PD patients with ICDs. The literature on ICDs in non-PD populations may also be informative in this regard. The goals of the present article are to outline important clinical characteristics of ICDs in PD, briefly review relevant neurocognitive and neurobiological studies and discuss possible ways to prevent and manage ICDs in PD.
| S-EPMC3627213 | biostudies-literature
Project description:Introduction: Impulse control disorders (ICDs) are a common complication of Parkinson's disease (PD) receiving dopamine agonist (DAA) Impulsivity is considered an underlying mechanism but evidence of this relationship is scarce. To explore the relationship between impulsivity and the presence and severity of ICD in PD. Methods: Prospective cross-sectional study of consecutive PD outpatients. Patients with dementia or previously known ICDs were excluded. Two measures of impulsivity were assessed: Barratt Impulsiveness Scale (BIS-11) for impulsiveness trait (main exposure) and commission errors in the Continuous Performance Test (CE) for motor inhibition. Main outcomes were diagnosis of ICD based on a comprehensive clinical interview and severity of ICD based on the Questionnaire for Impulsive-Compulsive Disorders. Results: Of 100 patients (mean [SD] age, 67.2 [8.8], 54 male), 31 had ICD. Patients with ICDs were 5.3 years younger (p = 0.01), used more frequently dopamine agonist (p = 0.02), alcohol (p = 0.009) and tobacco (p = 0.02). They were not more impulsive on BIS-11 (56 vs. 58, p = 0.23, adjusted p = 0.46) and CE (p = 0.96). No relationship was found between dopaminergic medications and impulsivity or ICD severity. Among patients with ICD, impulsivity was correlated with ICD severity (BIS-11 r = 0.33, p = 0.001, adjusted p = 0.002, CE r = 0.53, p = 0.006). Multivariate regression analysis confirmed the independent predictive role of both measures. Conclusions: Impulsivity is not associated with increased prevalence of ICD in PD but it is strongly linked to ICD severity. When considering dopamine replacement therapy, assessment of impulsivity may be a useful approach to detect those patients at risk of severe forms of ICD.
| S-EPMC6172299 | biostudies-literature
Project description:Introduction: Impulse control disorders (ICDs) frequently complicate dopamine agonist (DA) therapy in Parkinson's disease (PD). There is growing evidence of a high heritability for ICDs in the general population and in PD. Variants on genes belonging to the reward pathway have been shown to account for part of this heritability. We aimed to identify new pathways associated with ICDs in PD. Methods: Thirty-six Parkinsonian patients on DA therapy with (n = 18) and without ICDs (n = 18) matched on age at PD's onset, and gender was selected to represent the most extreme phenotypes of their category. Exome sequencing was performed, and variants with a strong functional impact in brain-expressed genes were selected. Allele frequencies and their distribution in genes and pathways were analyzed with single variant and SKAT-O tests. The 10 most associated variants, genes, and pathways were retained for replication in the Parkinson's progression markers initiative (PPMI) cohort. Results: None of markers tested passed the significance threshold adjusted for multiple comparisons. However, the "Adenylate cyclase activating" pathway, one of the top associated pathways in the discovery data set (p = 1.6 × 10-3) was replicated in the PPMI cohort and was significantly associated with ICDs in a post hoc pooled analysis (combined p-value 3.3 × 10-5). Two of the 10 most associated variants belonged to genes implicated in cAMP and ERK signaling (rs34193571 in RasGRF2, p = 5 × 10-4; rs1877652 in PDE2A, p = 8 × 10-4) although non-significant after Bonferroni correction. Conclusion: Our results suggest that genes implicated in the signaling pathways linked to G protein-coupled receptors participate to genetic susceptibility to ICDs in PD.
| S-EPMC7385236 | biostudies-literature
Project description:Impulse control disorders (ICDs) in Parkinson's disease (PD) have a high cumulative incidence and negatively impact quality of life. ICDs are influenced by a complex interaction of multiple factors. Although it is now well-recognized that dopaminergic treatments and especially dopamine agonists underpin many ICDs, medications alone are not the sole cause. Susceptibility to ICD is increased in the setting of PD. While causality can be challenging to ascertain, a wide range of modifiable and non-modifiable risk factors have been linked to ICDs. Common characteristics of PD patients with ICDs have been consistently identified across many studies; for example, males with an early age of PD onset and dopamine agonist use have a higher risk of ICD. However, not all cases of ICDs in PD can be directly attributable to dopamine, and studies have concluded that additional factors such as genetics, smoking, and/or depression may be more predictive. Beyond dopamine, other ICD associations have been described but remain difficult to explain, including deep brain stimulation surgery, especially in the setting of a reduction in dopaminergic medication use. In this review, we will summarize the demographic, genetic, behavioral, and clinical contributions potentially influencing ICD onset in PD. These associations may inspire future preventative or therapeutic strategies.
| S-EPMC6399407 | biostudies-literature