Nonmotor Symptoms and Impulse Control Disorders in Parkinson's Disease Patients in India: A Cross-sectional Study.

INTRODUCTION: Parkinson's disease (PD) is a prevalent neurodegenerative disorder with significant nonmotor symptom (NMS) burden, including impulse control disorders. This study aimed to comprehensively evaluate NMS and impulse control disorders in PD patients under primary care. MATERIALS AND METHODS: A descriptive cross-sectional study was conducted on 32 PD patients and evaluated using standardized assessment tools. Demographics, comorbidities, and symptom burdens were recorded. Evaluation tools included the Hoehn and Yahr Scale, REM Sleep Behavior Disorder assessment, Geriatric Depression Scale, Montreal Cognitive Assessment scale for cognitive impairment, NMS scale, and identification of impulse control disorders. RESULTS: In PD, comorbidities were prevalent (84%), and most were at Hoehn and Yahr Stages 2 and 3. REM Sleep Behavior Disorder was present in 28.12%, with 5 receiving clonazepam treatment. Depression affected 28.12%, with 5 receiving pharmacological treatment. Cognitive impairment was notable in 9 patients. NMS burden was high, with varying severity. Impulse control disorders were limited, whereas one case of dopamine dysregulation syndrome was identified. DISCUSSION: This primary care-based study in India assessed NMS and impulse control disorders in PD patients, highlighting comorbidities and management opportunities. The study's strength lies in evaluating an unselected primary care population, whereas limitations include small sample size. CONCLUSION: This study emphasizes the importance of primary care physicians in monitoring and managing NMS in PD patients. Impulse control disorders and cognitive impairment are critical aspects that need attention. The findings support an integrated approach involving health-care professionals across various disciplines to provide holistic care for PD patients.

Résumé Introduction:La maladie de Parkinson (PD) est un trouble neurodégénératif prévalent avec un fardeau significatif de symptômes non moteurs (NMS), y compris les troubles du contrôle des impulsions. Cette étude visait à évaluer de manière exhaustive les NMS et les troubles du contrôle des impulsions chez les patients atteints de la maladie de Parkinson pris en charge en soins primaires.Matériaux et méthodes:Une étude transversale descriptive a été menée sur 32 patients atteints de la maladie de Parkinson et évaluée à l'aide d'outils d'évaluation standardisés. Les données démographiques, les comorbidités et le fardeau des symptômes ont été enregistrés. Les outils d'évaluation comprenaient l'échelle de Hoehn et Yahr, l'évaluation du trouble du comportement en sommeil paradoxal (RBD), l'échelle de dépression gériatrique, l'échelle d'évaluation cognitive de Montréal pour les troubles cognitifs, l'échelle NMS et l'identification des troubles du contrôle des impulsions.Résultats:Chez les patients atteints de la maladie de Parkinson, les comorbidités étaient prévalentes (84 %), et la plupart étaient aux stades 2 et 3 de l'échelle de Hoehn et Yahr. Le trouble du comportement en sommeil paradoxal était présent chez 28,12 % des patients, dont 5 recevaient un traitement au clonazépam. La dépression affectait 28,12 % des patients, dont 5 recevaient un traitement pharmacologique. Une altération cognitive était notable chez 9 patients. Le fardeau des NMS était élevé, avec une gravité variable. Les troubles du contrôle des impulsions étaient limités, tandis qu'un cas de syndrome de dysrégulation dopaminergique a été identifié.Discussion:Cette étude menée en soins primaires en Inde a évalué les NMS et les troubles du contrôle des impulsions chez les patients atteints de la maladie de Parkinson, mettant en évidence les comorbidités et les opportunités de prise en charge. La force de l'étude réside dans l'évaluation d'une population de soins primaires non sélectionnée, tandis que les limites comprennent une petite taille d'échantillon.Conclusion:Cette étude souligne l'importance des médecins de soins primaires dans la surveillance et la prise en charge des NMS chez les patients atteints de la maladie de Parkinson. Les troubles du contrôle des impulsions et l'altération cognitive sont des aspects critiques qui nécessitent une attention particulière. Les résultats soutiennent une approche intégrée impliquant des professionnels de la santé de différentes disciplines pour fournir des soins holistiques aux patients atteints de la maladie de Parkinson.

Impulse control disorders in patients with dopamine agonist-treated pituitary adenomas: a cross-sectional multicenter study.

BACKGROUND: Impulse control disorders (ICDs) have been described as underrecognized side effects of dopamine agonists (DAs) in neurological disorders but are not sufficiently understood in endocrine conditions. OBJECTIVE: To identify the prevalence of DAs induced ICDs and determine potential risk factors related to these disorders in patients with prolactinoma and non-function pituitary adenomas (NFPAs). METHODS: This is a cross-sectional multicenter study involving 200 patients with prolactinoma and NFPAs, who received follow-ups in tertiary referral centers. DA-induced ICDs were assessed using ICD questionnaires modified from prior studies. RESULT: At least one ICD was reported by 52% of participants, among whom 28.5% mentioned compulsive shopping, 24.5% punding, and 24.5% hypersexuality. Furthermore, 33% of the patients reported the presence of one type of ICD behavior, while 12% specified two and 7% had three types of such behavior. The multivariable logistic regression showed that the significant risk factors of ICD were younger age (adjusted odds ratio [AOR]: 0.92, 95% confidence interval [CI]: 0.88-0.97, p 0.001), being single (AOR: 0.15, 95%CI: 0.03-0.84, p 0.03), and a positive history of psychiatric illness (AOR: 7.67, 95% CI: 1.37-42.97, p 0.021). CONCLUSION: ICDs with a broad range of psychiatric symptoms are common in individuals with DA-treated prolactinoma and NFPAs. Endocrinologists should be aware of this potential side effect, particularly in patients with a personal history of psychiatric disorder.

Impulse control behaviors and apathy commonly co-occur in de novo Parkinson's disease and predict the incidence of levodopa-induced dyskinesia.

OBJECTIVE: Impulse control behaviors (ICBs) and apathy are believed to represent opposite motivational expressions of the same behavioral spectrum involving hypo- and hyperdopaminergic status, but this has been recently debated. Our study aims to estimate the co-occurrence of ICBs and apathy in early Parkinson's disease (PD) and to determine whether this complex neuropsychiatric condition is an important marker of PD prognoses. METHODS: Neuropsychiatric symptoms, clinical data, neuroimaging results, and demographic data from de novo PD patients were obtained from the Parkinson's Progression Markers Initiative, a prospective, multicenter, observational cohort. The clinical characteristics of ICBs co-occurring with apathy and their prevalence were analyzed. We compared the prognoses of the different groups during the 8-year follow-up. Multivariate Cox regression analysis was conducted to predict the development of levodopa-induced dyskinesia (LID) using baseline neuropsychiatric symptoms. RESULTS: A total of 422 PD patients and 195 healthy controls (HCs) were included. In brief, 87 (20.6 %) de novo PD patients and 37 (19.0 %) HCs had ICBs at baseline. Among them, 23 (26.4 %) de novo PD patients and 3 (8.1 %) HCs had clinical symptoms of both ICBs and apathy. The ICBs and apathy group had more severe non-motor symptoms than the isolated ICBs group. Cox regression analysis demonstrated that the co-occurrence of ICBs and apathy was a risk factor for LID development (HR 2.229, 95 % CI 1.209 to 4.110, p = 0.010). CONCLUSIONS: Co-occurrence of ICBs and apathy is common in patients with early PD and may help to identify the risk of LID development.

The Association of Antidepressant Use and Impulse Control Disorder in Parkinson's Disease.

OBJECTIVES: To examine whether initiation of an antidepressant is associated with the development of impulse control disorder (ICD) in patients with Parkinson's disease (PD). DESIGN: We performed a retrospective analysis utilizing data from the Parkinson's Progression Markers Initiative (PPMI). Two-sample Mann-Whitney tests were used for comparison of continuous variables and Pearson χ2 tests were used for categorical variables. Kaplan-Meier survival analysis and cox proportional hazards regression analysis was used to assess the hazard of ICD with antidepressant exposure. SETTING: The PPMI is a multicenter observational study of early PD with 52 sites throughout North America, Europe, and Africa. PARTICIPANTS: Participants in the current study were those in the PPMI PD cohort with a primary diagnosis of idiopathic PD. MEASUREMENTS: The presence of ICD was captured using the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease (QUIP). Antidepressant use was defined based on medication logs for each participant. Depressive symptoms were captured using the Geriatric Depression Scale (GDS). RESULTS: A total of 1,045 individuals were included in the final analysis. There was a significant increase in the probability of ICD in those exposed to serotonergic antidepressants compared to those not exposed (Log-rank p <0.001). Serotonergic antidepressant use was associated with a hazard ratio for ICD of 1.4 (95% CI 1.0-1.8, z-value 2.1, p = 0.04) after adjusting for dopamine agonist use, depression, bupropion use, MAOI-B use, amantadine use, LEDD, disease duration, sex, and age. CONCLUSIONS: Serotonergic antidepressant use appears to be temporally associated with ICD in patients with PD.

Impulse control disorders in Parkinson's disease: a retrospective analysis of 1824 patients in a 12-year period.

OBJECTIVE: This study aims to clinically evaluate the impulse control disorders (ICDs) encountered in treating Parkinson's disease. METHOD: This is a retrospective analysis between 2010 and 2022. We retrieved the medical records of all patients diagnosed with idiopathic Parkinson's disease. The demographic and clinical findings were recorded. ICDs constituted a specific item in the examination, and each one (compulsive shopping, compulsive eating, pathological gambling, hypersexuality, punding, dopamine dysregulation syndrome, and hobbyism) was noted separately. RESULTS: In the study period, we identified 1824 patients (56.2% men, n = 1025). The mean age was 70.5 ± 11.9 years. In the cohort, 128 (7%) patients with Parkinson's disease had one or more ICDs. The ICDs were compulsive shopping, punding/hobbyism, compulsive eating, hypersexuality, pathological gambling, and dopamine dysregulation syndrome. When we compared patients with and without ICDs, patients with ICDs were younger (p ≤ 0.001), and the men/women ratio was higher in this group with ICDs. Although the mean daily pramipexole dose was higher in patients with ICDs, mean daily long-acting pramipexole dose was only 1.4 ± 0.92 mg/day. CONCLUSION: The significant findings in this study were (i) the lower frequency of ICDs (7%); (ii) the common occurrence of compulsive shopping, punding/hobbyism, and compulsive eating; and (iii) the development of ICDs under relatively lower doses of pramipexole. We suggest that ICDs in Parkinson's disease should be associated with a personal trait with dopamine agonists, and potential electrophysiological or genetic markers of this trait warrant further analysis to avoid treatment in these patients.

Disorders of impulsivity in trichotillomania and skin picking disorder.

Trichotillomania and skin picking disorder are often classified as body-focused repetitive behaviors (BFRBs) as they are characterized by repetitive hair-pulling and skin picking, respectively. They were initially considered to be impulse control disorders despite little research scrutiny. The objective of this study was to examine the relationship of these two conditions to other disorders with impulsive features. Adults with trichotillomania (n = 104) and skin picking (n = 178) or both (n = 96) were recruited from the general community using advertisements and online support groups and completed an online survey. Participants undertook a structured clinical interview and completion of self-report instruments to characterize clinical profiles and associated characteristics. In addition, each participant completed the Minnesota Impulse Disorders Interview to screen for disorders with impulsive features. Of the 378 adults with BFRBs, 134 (35.4%) screened positive for at least one disorder with features of impulsivity with the most common being compulsive buying (18.3%) and problematic use of the internet (17.5%). Participants with a co-occurring disorder of impulsivity reported significantly worse pulling and picking symptoms (p < .001), were more likely to have co-occurring alcohol problems (p < .001) and PTSD (p < .001), and scored higher regarding dissociative symptoms (p < .001). BFRBs are associated with a range of impulsive disorders and the comorbidity may have important treatment implications.

Frequency of Impulsive-Compulsive Behavior and Associated Psychological Factors in Parkinson's Disease: Lack of Control or Too Much of It?

Background and Objectives: Impulse Control Disorders (ICDs) including pathological gambling, hypersexuality, compulsive eating, compulsive buying, and other related behaviors are well-known distinct non-motor symptoms in Parkinson's Disease (PD). Some large-scale studies present a prevalence of at least 10%, however, there are other reports providing much higher rates. The majority of the conducted studies investigating ICDs focus mainly on pharmacological factors, however, from a psychological perspective, there is yet enough room for investigation. In order to address the above issues, we designed a two-part study. Materials and Methods: First, we aimed to identify the incidence of ICD and related behaviors in a cohort of 892 Greek PD patients. Second, we administered a comprehensive battery of psychometric tools to assess psychological factors such as personality dimensions, quality of life, defenses, coherence, and resilience as well as to screen general cognitive capacity in PD patients with ICD manifestations. Results: With regard to the first part, we identified ICD manifestations in 12.4% of the patients. Preliminary findings from the second part indicate elevated activity, rather than impulsivity, as well as interrelations between several variables, including measures of activity, coping mechanisms, and quality of life. Conclusions: We present a working hypothesis for the contribution of high activity channeled to specific behavioral patterns through specific coping mechanisms, concerning the emergence of ICDs and related behaviors in PD, and further stress the importance of compulsivity rather than impulsivity in this process.

Impulse Control Disorders in Patients with Pituitary Tumors Treated with Dopamine Agonists: A Systematic Review.

BACKGROUND: The increased prevalence of Impulse Control Disorders (ICDs) in dopamine agonist (DA) treated patients with Parkinson's disease is well described. Despite the frequent use of DAs in the management of pituitary tumors, the relationship between DAs and prevalence of ICDs in patients with pituitary tumours is unclear. AIMS: To establish the prevalence of ICDs in patients with prolactinoma or acromegaly and determine whether prevalence differs in those on DAs to those treated without. METHODS: Systematic review of the literature (registered a priori) reporting prevalence of ICDs in patients with prolactinoma or acromegaly (conducted June 2023). A narrative synthesis describing prevalence of ICDs according to assessment method was performed. Prevalence comparisons between patients with prolactinoma or acromegaly treated with DAs, to patients treated without, were summarised. RESULTS: Studies were largely retrospective, observational and heterogenous, with few patients with prolactinoma and acromegaly treated without DA. Prevalence of ICDs varied between 0-60% in patients with prolactinoma, and from 5-23% in studies with at least five patients with acromegaly. In most studies comparing DA exposed to non-DA exposed cases, DA use was not associated with ICDs. CONCLUSIONS: Reported prevalence of ICDs in patients with prolactinoma and acromegaly varies considerably. Given ICDs were reported to be highly prevalent in some studies, clinicians should be mindful of these potentially serious disorders. ICD screening tools validated for use in patients with pituitary tumors combined with prospective studies including appropriate controls, are necessary to accurately establish prevalence of ICDs and true impact of DAs in their development.

Electroencephalogram-Driven Machine-Learning Scenario for Assessing Impulse Control Disorder Comorbidity in Parkinson's Disease Using a Low-Cost, Custom LEGO-Like Headset.

Patients with Parkinson's disease (PD) may develop cognitive symptoms of impulse control disorders (ICDs) when chronically treated with dopamine agonist (DA) therapy for motor deficits. Motor and cognitive comorbidities critically increase the disability and mortality of the affected patients. This study proposes an electroencephalogram (EEG)-driven machine-learning scenario to automatically assess ICD comorbidity in PD. We employed a classic Go/NoGo task to appraise the capacity of cognitive and motoric inhibition with a low-cost, custom LEGO-like headset to record task-relevant EEG activity. Further, we optimized a support vector machine (SVM) and support vector regression (SVR) pipeline to learn discriminative EEG spectral signatures for the detection of ICD comorbidity and the estimation of ICD severity, respectively. With a dataset of 21 subjects with typical PD, 9 subjects with PD and ICD comorbidity (ICD), and 25 healthy controls (HC), the study results showed that the SVM pipeline differentiated subjects with ICD from subjects with PD with an accuracy of 66.3% and returned an around-chance accuracy of 53.3% for the classification of PD versus HC subjects without the comorbidity concern. Furthermore, the SVR pipeline yielded significantly higher severity scores for the ICD group than for the PD group and resembled the ICD vs. PD distinction according to the clinical questionnaire scores, which was barely replicated by random guessing. Without a commercial, high-precision EEG product, our demonstration may facilitate deploying a wearable computer-aided diagnosis system to assess the risk of DA-triggered cognitive comorbidity in patients with PD in their daily environment.

Impulse Control Disorders in the Polish Population of Patients with Parkinson's Disease.

Background and Objectives: Parkinson's disease (PD) is one of the most common neurodegenerative diseases in the world. It is characterized by the presence of not only typical motor symptoms but also several less known and aware non-motor symptoms (NMS). The group of disorders included in the NMS is Impulse Control Disorders (ICDs). ICDs are a group of disorders in which patients are unable to resist temptations and feel a strong, pressing desire for specific activities such as gambling, hypersexuality, binge eating, and compulsive buying. The occurrence of ICDs is believed to be associated primarily with dopaminergic treatment, with the use of dopamine agonists (DA), and to a lesser extent with high doses of L-dopa. The aim of our study was to develop a profile of Polish ICDs patients and assess the frequency of occurrence of ICDs, as well as determine the risk factors associated with these disorders against the background of the PD population from other countries. Materials and Methods: Our prospective study included 135 patients with idiopathic PD who were hospitalized between 2020 and 2022 at the Neurological Department of University Central Hospital in Katowice. In the assessment of ICDs, we used the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease (QUIP). Other scales with which we assessed patients with PD were as follows: MDS-UPDRS part III and modified Hoehn-Yahr staging. Clinical data on age, gender, disease duration and onset, motor complications, and medications were collected from electronic records. Results: ICDs were detected in 27.41% of PD patients (binge eating in 12.59%, hypersexuality in 11.11%, compulsive buying in 10.37%, and pathological gambling occurred in only 5.19% of patients. In total, 8.89% had two or more ICDs). The major finding was that ICDs were more common in patients taking DA than in those who did not use medication from this group (83.78% vs. 54.07%, respectively; p = 0.0015). Patients with ICDs had longer disease duration, the presence of motor complications, and sleep disorders. An important finding was also a very low detection of ICDs in a routine medical examination; only 13.51% of all patients with ICDs had a positive medical history of this disorder. Conclusions: ICDs are relatively common in the population of Polish PD patients. The risk factors for developing ICDs include longer duration of the disease, presence of motor complications, sleep disorders, and use of DA and L-dopa. Due to the low detectability of ICDs in routine medical history, it is essential for physicians to pay more attention to the possibility of the occurrence of these symptoms, especially in patients with several risk factors. Further prospective studies on a larger group of PD patients are needed to establish a full profile of Polish PD patients with ICDs.

The mediating effects of depression, anxiety, and rapid eye movement sleep behavior disorder on the association between dopaminergic replacement therapy and impulse control disorders in Parkinson's disease.

OBJECTIVES: This study aims to longitudinally explore whether and how rapid eye movement sleep behavior disorder (RBD), depression, and anxiety mediate the association between dopaminergic replacement therapy (DRT) and impulse control disorders (ICDs) in patients with Parkinson's disease (PD). METHODS: Subjects were selected from the Parkinson's Progression Markers Initiative. After excluding missing data, 268, 223, 218, 238, and 219 patients with PD diagnosed at 12, 24, 36, 48, and 60 months prior, respectively, were included. We used the Questionnaire for Impulsive-Compulsive Disorders, RBD Screening Questionnaire, Geriatric Depression Scale, and State-Trait-Anxiety Inventory to assess ICBs, RBD, depression, and anxiety, respectively. We constructed three causal mediation analysis models to infer potential contingent pathways from DRT to ICD mediated by depression, anxiety, and RBD separately. RESULTS: DRT was associated with an increased risk of PD incidence. Aggravation of ICDs was partly explained by improvements in depression (the average causal mediation effect accounted for 8.0% of the total effect) and RBD (the average causal mediation effect of RBD accounted for 16.4% of the total effect). This suggested that anxiety (the average causal mediation effect accounted for 12.7% of the total effect) plays a mediating role. CONCLUSIONS: Focusing on changes in RBD, depression, and anxiety associated with hyperdopaminergic status should be an essential part of strategies to prevent ICDs in patients with Parkinson's disease.

Impulse control disorders associated with dopaminergic drugs: A disproportionality analysis using vigibase.

BACKGROUND: Dopamine receptor agonist drugs, which are used, for example, to treat Parkinson's disease (PD), increase the risk for impulse control disorders (ICDs), potentially resulting in devastating psychosocial consequences. It is unknown whether other drugs with dopaminergic properties also increase the risk for ICDs. This study assesses the disproportionality of reporting ICDs between drugs with dopaminergic properties and selected non-dopaminergic drugs. METHODS: A case/non-case disproportionality analysis was performed, using data from VigiBase (1968-2020). Reports on ICDs as suspected adverse drug reactions (ADRs) were cases (n=852), and those with ADRs other than ICDs were non-cases (n=281,720). Relative reporting frequencies were expressed as adjusted reporting odds ratios (aRORs). Within the dopamine receptor agonists, the relationship between reporting odds ratios and dopamine receptor occupancy was explored. RESULTS: A high disproportionality was found for reporting ICDs for all dopaminergic drugs (aROR 20.4 [95% CI 17.4-24.1]) compared to non-dopaminergic drugs. In pharmacotherapeutic subgroups, a high disproportionality was found for primary dopaminergic agents used in PD (aROR 52.1 [95% CI 44.1-61.5]), and to a lesser extent for ADHD psychostimulants and antidepressants (aROR 5.8 [95% 4.1-8.3] and aROR 3.9 [95% CI 2.9-5.6], respectively). There was no difference in reporting by consumers and healthcare professionals. The highest disproportionality was found for the dopamine receptor agonists pramipexole and ropinirole. CONCLUSIONS: A signal of disproportion in ICD occurrence was found among all investigated drugs with dopaminergic properties, highlighting the importance of counselling and monitoring for ICDs when prescribing dopaminergic drugs.

Assessment of subjective sleep quality and issues in aggression: Intermittent Explosive Disorder compared with psychiatric and healthy controls.

BACKGROUND: While prior research has linked clinical sleep issues and aggression, little is known about how clinical sleep issues among individuals with Intermittent Explosive Disorder (IED), which is characterized by a pervasive pattern of impulsive aggression and associated with consequences across multiple life-domains. The present study aims to examine clinical sleep issues among individuals with IED in contrast to individuals with other psychopathology and healthy controls. METHODS: 257 adults, including 100 healthy controls, 85 psychiatric controls and 72 individuals with IED, took part in this study. Participants completed the Structured Clinical Interview for DSM-V Diagnoses, Assessment of clinical sleep issues included the Pittsburgh Sleep Quality Inventory (PSQI), obstructive sleep apnea (OSA) screening, and the Epworth Sleepiness Scale (ESS) as well as assessments of aggression and impulsivity. RESULTS: IED study participants reported significantly worse sleep quality, increased sleep latency, greater daytime sleepiness and symptoms of OSA. Daytime sleepiness and sleep quality was correlated with impulsivity and aggression. CONCLUSIONS: This study suggests that individuals with IED have clinically relevant sleep anomalies, and that these are directly associated with measures of impulsivity and aggression. Clinicians treating aggressive individuals are advised to assess and treat such individuals for sleep issues.

ADHD symptom profiles, intermittent explosive disorder, adverse childhood experiences, and internalizing/externalizing problems in young offenders.

Attention-deficit/hyperactivity disorder (ADHD) and co-existing psychiatric/psychological impairments as well as adverse childhood experiences (ACEs) are common among young offenders. Research on their associations is of major importance for early intervention and crime prevention. Intermittent explosive disorder (IED) warrants specific consideration in this regard. To gain sophisticated insights into the occurrence and associations of ADHD, IED, ACEs, and further psychiatric/psychological impairments in young (male and female) offenders, we used latent profile analysis (LPA) to empirically derive subtypes among 156 young offenders who were at an early stage of crime development based on their self-reported ADHD symptoms, and combined those with the presence of IED. We found four distinct ADHD subtypes that differed rather quantitatively than qualitatively (very low, low, moderate, and severe symptomatology). Additional IED, ACEs, and further internalizing and externalizing problems were found most frequently in the severe ADHD subtype. Furthermore, females were over-represented in the severe ADHD subtype. Finally, ACEs predicted high ADHD symptomatology with co-existing IED, but not without IED. Because ACEs were positively associated with the occurrence of ADHD/IED and ADHD is one important risk factor for on-going criminal behaviors, our findings highlight the need for early identification of ACEs and ADHD/IED in young offenders to identify those adolescents who are at increased risk for long-lasting criminal careers. Furthermore, they contribute to the debate about how to best conceptualize ADHD regarding further emotional and behavioral disturbances.

Impulse control disorders and related behaviors in Parkinson's disease: risk factors, clinical and genetic aspects, and management.

PURPOSE OF REVIEW: To review recent findings and research directions on impulse control disorders and related behaviors (ICDRBs) in Parkinson's disease (PD). RECENT FINDINGS: Longitudinal studies found that prevalence increases during PD progression, incident ICDRBs being around 10% per year in patients treated with dopaminergic therapies. Screening tools and severity scales already developed have been validated and are available in several countries and languages. The main clinical risk factors include young age, male gender, type, doses and duration of dopaminergic therapy, PD motor severity and dyskinesia, depression, anxiety, apathy, sleep disorders, and impulsivity traits. Genetic factors are suspected by a high estimated heritability, but individual genes and variants remain to be replicated. Management of ICDRBs is centered on dopamine agonist decrease, with the risk to develop withdrawal symptoms. Cognitive behavioral therapy and subthalamic nucleus deep brain stimulation also improve ICDRBs. In the perspective of precision medicine, new individual prediction models of these disorders have been proposed, but they need further independent replication. SUMMARY: Regular monitoring of ICDRB during the course of PD is needed, particularly in the subject at high risk of developing these complications. Precision medicine will require the appropriate use of machine learning to be reached in the clinical setting.

Prevalence and psychiatric comorbidities of intermittent explosive disorders in Metropolitan São Paulo, Brazil.

PURPOSE: To estimate the prevalence of intermittent explosive disorder (IED) in comorbidity with other psychiatric disorders and to describe the temporal sequencing of disorders in the São Paulo Metropolitan Area, Brazil. METHODS: Data from the São Paulo Megacity Mental Health Survey, a population-based study of 5037 adult individuals, were analyzed. The World Health Organization Composite International Diagnostic Interview (CID 3.0) was used to assess lifetime DSM-IV disorders, including IED, with a response rate of 81.3%. RESULTS: The majority (76.8%) of respondents with IED meet the criteria for at least one other psychiatric disorder, with a prevalence almost twice as high as that observed in individuals without IED. The prevalence of any anxiety, mood, impulse control or substance use disorders in respondents with IED was more than two times higher compared to those without IED, with prevalence ratios ranging from 2.1 (95% CI 1.74-2.48) to 2.9 (95% CI 2.12-4.06). The diagnosis of IED occurred earlier than most of the other mental disorders, except for those with usual onset in early childhood, as Specific and Social Phobias and Attention Deficit Disorder. CONCLUSION: Considering that IED is a highly comorbid disorder and has an earlier onset than most other mental comorbidities in the Brazilian general population, these results may be useful in guiding governmental mental health actions.

Integrating genetic and clinical data to predict impulse control disorders in Parkinson's disease.

BACKGROUND AND PURPOSE: Impulse control disorders (ICDs) are frequent in Parkinson's disease (PD), with associated clinical and genetic risk factors. This study was aimed at analyzing the clinical features and the genetic background that underlie ICDs in PD. METHODS: We included 353 patients with PD in this study (58.9% men, mean age 62.4 ± 10.58 years, mean age at disease onset 52.71 ± 11.94 years). We used the validated Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease for ICDs screening. Motor, nonmotor, and treatment-related features were evaluated according to the presence of ICDs. Twenty-one variants related to dopaminergic, serotonergic, glutamatergic, and opioid neurotransmitter systems were assessed. Association studies between polymorphisms and ICDs were performed. The combination of clinical and genetic variables was analyzed with receiver operating characteristic curves to assess the predictability of experiencing ICDs. RESULTS: Impulse control disorders appeared in 25.1% of the cases. Patients with ICDs were younger and presented a higher rate of anxiety. Treatment with dopamine agonists increased the risk of ICDs and it was dose dependent (P < 0.05). Genetic association studies showed that the DOPA decarboxylase gene (DDC), rs1451375, might modulate the risk of ICDs. Plotting the clinical-genetic model, the predictability of ICDs increased 11% (area under curve = 0.80; z = 3.22, P = 0.001) when adding the genotype data for single nucleotide polymorphisms. CONCLUSIONS: Polymorphisms in DDC might act as risk markers for ICDs in PD. The predictability of experiencing ICDs increased by adding genetic factors to clinical features. It is therefore important to assess the patient's genetic background to identify individuals at risk for ICDs.

Increased prevalence of impulse control disorder symptoms in endocrine diseases treated with dopamine agonists: a cross-sectional study.

INTRODUCTION: Impulse control disorders (ICDs) have been described as a side effect of dopamine agonists (DAs) in neurological as well as endocrine conditions. Few studies have evaluated the neuropsychological effect of DAs in hyperprolactinemic patients, and these have reported a relationship between DAs and ICDs. Our objective was to screen for ICD symptoms in individuals with DA-treated endocrine conditions. MATERIALS AND METHODS: A cross-sectional analysis was conducted on 132 patients with pituitary disorders treated with DAs (DA exposed), as well as 58 patients with pituitary disorders and no history of DA exposure (non-DA exposed). Participants responded to the full version of the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's disease (QUIP). RESULTS: Compared with the non-DA-exposed group, a higher prevalence of DA-exposed patients tested positive for symptoms of any ICD or related behavior (52% vs. 31%, p < 0.01), any ICD (46% vs. 24%, p < 0.01), any related behavior (31% vs. 17%, p < 0.05), compulsive sexual behavior (27% vs. 14%, p < 0.04), and punding (20% vs. 7%, p < 0.02) by QUIP. On univariate analysis, DA treatment was associated with a two- to threefold increased risk of any ICD or related behavior [odds ratio (OR) 2.43] and any ICD (OR 2.70). In a multivariate analysis, independent risk factors for any ICD or related behavior were DA use (adjusted OR 2.22) and age (adjusted OR 6.76). Male gender was predictive of the risk of hypersexuality (adjusted OR 3.82). DISCUSSION: Despite the QUIP limitations, a clear sign of increased risk of ICDs emerges in individuals with DA-treated pituitary disorders. Our data contribute to the growing evidence of DA-induced ICDs in endocrine conditions.

Depression is Associated with Impulse-compulsive Behaviors in Parkinson's disease.

BACKGROUND: Depression and impulse control disorders (ICDs) are both common in Parkinson's disease (PD) patients and their coexistence is frequent. Our aim was to determine the relationship between depression and impulsive-compulsive behaviors (ICBs) in a large cohort of PD patients. METHODS: PD patients recruited from 35 centers of Spain from the COPPADIS cohort from January 2016 to November 2017 were included in the study. The QUIP-RS (Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale) was used for screening ICDs (cutoff points: gambling ≥6, buying ≥8, sex≥8, eating≥7) and compulsive behaviors (CBs) (cutoff points: hobbyism-punding ≥7). Mood was assessed with the BDI-II (Beck Depression Inventory - II) and major, minor, and subthreshold depression were defined. RESULTS: Depression was more frequent in PD patients with ICBs than in those without: 66.3% (69/104) vs 47.5% (242/509); p<0.0001. Major depression was more frequent in this group as well: 22.1% [23/104] vs 14.5% [74/509]; p=0.041. Considering types of ICBs individually, depression was more frequent in patients with pathological gambling (88.9% [8/9] vs 50.2% [303/603]; p=0.021), compulsive eating behavior (65.9% [27/41] vs 49.7% [284/572]; p=0.032), and hobbyism-punding (69% [29/42] vs 49.4% [282/571]; p=0.010) than in those without, respectively. The presence of ICBs was also associated with depression (OR=1.831; 95%CI 1.048-3.201; p=0.034) after adjusting for age, sex, civil status, disease duration, equivalent daily levodopa dose, antidepressant treatment, Hoehn&Yahr stage, non-motor symptoms burden, autonomy for activities of daily living, and global perception of QoL. LIMITATIONS: Cross-sectional design. CONCLUSIONS: Depression is associated with ICBs in PD. Specifically, with pathological gambling, compulsive eating behavior, and hobbyism-punding.