Risk Of Impulse Control Disorders Research Articles

Aripiprazole and Other Third-Generation Antipsychotics as a Risk Factor for Impulse Control Disorders: A Systematic Review and Meta-Analysis.

Increasing evidence suggests an association between third-generation antipsychotics (TGAs) and impulse control disorders (ICDs). This is thought to be due to their partial agonism of dopamine receptors. However, neither the relative nor absolute risks of ICDs in those prescribed TGAs are well established. To inform clinical practice, this systematic review and meta-analysis summarizes and quantifies the current evidence for an association. An electronic search of Medline, PsychINFO, EMBASE, and the Cochrane Clinical Trials Database was undertaken from database inception to November 2022. Three reviewers screened abstracts and reviewed full texts for inclusion. A random-effects meta-analysis was conducted with eligible studies. A total of 392 abstracts were retrieved, 214 remained after duplicates were removed. Fifteen full texts were reviewed, of which 8 were included. All 8 studies found that TGAs were associated with increased probability of ICDs. Risk of bias was high or critical in 7 of 8 studies. Three studies were included in the pooled analysis for the primary outcome, 2 with data on each of aripiprazole, cariprazine, and brexpiprazole. Exposure to TGAs versus other antipsychotics was associated with an increase in ICDs (pooled odds ratio, 5.54; 2.24-13.68). Cariprazine and brexpiprazole were significantly associated with ICDs when analyzed individually. Aripiprazole trended toward increased risk, but very wide confidence intervals included no effect. Third-generation antipsychotics were associated with increased risk of ICDs in all studies included and pooled analysis. However, the risk of bias is high, confidence intervals are wide, and the quality of evidence is very low for all TGAs examined.

Dopamine agonist serum concentrations and impulse control disorders in Parkinson's disease.

Impulse control disorders (ICDs) are common among Parkinson's disease patients using dopamine agonists. We wanted to determine whether ICD patients have higher dopamine agonist serum concentrations than those without any sign of ICD. Patients who used either pramipexole or ropinirole depot once daily were screened for ICDs using the validated Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale. Those who scored above the cut-off for one or more of the four defined ICDs (gambling, compulsive sexual behavior, compulsive shopping, and binge-eating) were compared in a case-control study to patients who scored zero points (no evidence of ICD) on the same items. They were examined clinically and evaluated using relevant scales. Three blood samples were taken on the same day: before daily dose, and then 6 and 12 h later. Forty-six patients were included: 19 ICD-positive and 27 controls. Ropinirole serum concentrations 6 h after daily intake (Cmax ) were higher in the case group compared to the control group, as was the daily ropinirole dosage. No differences were observed in serum concentrations, dosage or total drug exposure for pramipexole. Disease duration and length of dopamine agonist treatment was significantly longer among ICD patients for ropinirole, but not for pramipexole. The use of pramipexole may in itself confer high ICD risk, whereas ICDs among ropinirole users depend more on serum concentration and drug exposure. The pharmacokinetic properties of ropinirole make it challenging to predict its effects on patients, which supports the need for therapeutic drug monitoring to reduce risk of ICD.

Risk of impulse control disorders in patients with Cushing's disease: do not blame cabergoline but do not give up caution.

To asses risk of new-onset impulse control disorders (ICDs) in patients with Cushing's disease (CD) who initiated cabergoline (CBG) and to determine frequency of ICDs in CBG-treated patients with CD. This naturalistic observational study had prospective and cross-sectional arms which included patients at five referral centers based in Istanbul. Patients who were scheduled for CBG were assigned to prospective arm. These patients underwent neuropsychological tests (Barratt Impulsiveness Scale, Minnesota Impulsive Disorders Interview, Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale, Go/No-Go Task, Iowa Gambling Task, and Short Penn Continuous Performance Test) for assessment of impulsivity and psychiatric evaluations at baseline, 3, 6, and 12months of CBG treatment. Impulsivity and new-onset ICDs were prospectively assessed. Patients with CD with current CBG treatment for ≥ 3months and matched CBG-naïve patients with CD were included in cross-sectional arm. These patients underwent the same neuropsychological and psychiatric assessments. The impulsivity and frequency of ICDs were compared between CBG-treated and CBG-naïve patients with CD. The follow-up duration of prospective cohort (n = 14) was 7.3 ± 2.3months. One patient developed major depressive episode and another patient developed compulsive gambling after CBG. We observed no significant changes in impulsivity scores during follow-up. In cross-sectional arm, CBG-treated (n = 34) and CBG-naïve patients (n = 34) were similar in impulsivity scores and frequency of ICDs [3 patients (8.8%) vs. 2 patients (5.9%) respectively, p = 1.0]. CBG-treated patients with CD appeared to have a low risk of ICDs, suggesting that CBG still holds promise as a safe agent in CD.

Risk of Impulse Control Disorders in Cabergoline-Treated Cushing's Disease: A Cross-sectional Study

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Effect of Dopaminergic Therapy on Impulse Control Disorders in Patients With a Prolactinoma.

Studies have reported an increase in the incidence of impulse control disorders (ICDs) in patient groups treated with dopamine agonists (DAAs), especially in Parkinson disease (PD). However, very few studies have reported on ICDs in individuals with a prolactinoma who were treated with DAAs. To see whether a DAA by itself causes ICDs in individuals with a prolactinoma by controlling the susceptibility to impulsivity by excluding individuals with other risk factors for ICDs. We compared the performance of 31 individuals with a prolactinoma receiving DAA therapy (DAA+) on various behavioral scales and the Iowa gambling task (IGT), a neuropsychological instrument that measures risky decision-making, with the performance of 20 individuals with a prolactinoma who were not on DAA therapy (DAA-) and 30 healthy controls (HC). There was no significant difference among the groups concerning performance on the Zuckerman Sensation Seeking Scale-V, Minnesota Impulse Disorders Interview, Barratt Impulsiveness Scale-11, or IGT. No correlation was found between the scores on these scales and the duration or dose of DAA in the DAA+ group. The incidence of ICDs was 25.8% in the DAA+ group, 15% in the DAA- group, and 16.7% in the HC. The differences among the groups did not reach statistical significance. Individuals who are under treatment with low-dose, D 2 -selective DAAs for a prolactinoma do not face an increased risk for ICDs, especially when they are carefully screened for any psychiatric comorbidity that may also display impulsivity.

Impulse control disorders in hyperprolactinemic patients on dopamine agonist therapy.

Dopamine agonists (DAs) represent a mainstay of therapy for hyperprolactinemia and prolactinomas. The widespread use of DAs, including bromocriptine, cabergoline and (in some countries) quinagolide, has led to the emergence and recognition of impulse control disorders (ICDs) that may occur in association with DA therapy.Such ICDs include pathological gambling, compulsive shopping, hypersexuality and punding (the performance of repetitive tasks), among others. These manifestations can lead to substantial harms to patients and their families, if left undiagnosed and untreated. Several risk factors that may increase the risk of ICDs have been proposed, including younger age, male gender, smoking and alcohol use and history of depression.The diagnosis of ICDs in hyperprolactinemic patients treated with DAs requires a high index of suspicion and a systematic approach, using available screening questionnaires. However, it should be noted that available test instruments, including questionnaires and computerized tasks, have not been validated specifically in hyperprolactinemic patients. Hyperprolactinemic patients who develop ICDs should be withdrawn from DA therapy or, at a minimum, undergo a DA dose reduction, and considered for psychiatric consultation and cognitive behavioral therapy. However, the role of psychopharmacotherapy in hyperprolactinemic patients with ICDs remains incompletely characterized.Patient counseling regarding the risk of ICDs occurring in association with DA therapy, early detection and prompt intervention may mitigate potential harms associated with ICDs. Additional studies are needed to fully characterize risk factors, underlying mechanisms and identify effective therapies for ICDs in patients with hyperprolactinemia receiving DAs.

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

BackgroundDopamine 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. MethodsA 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. ResultsA 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. ConclusionsA 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.

Dopaminergic Therapy for Motor Symptoms in Early Parkinson Disease Practice Guideline Summary: A Report of the AAN Guideline Subcommittee.

To review the current evidence on the options available for initiating dopaminergic treatment of motor symptoms in early-stage Parkinson disease and provide recommendations to clinicians. A multidisciplinary panel developed practice recommendations, integrating findings from a systematic review and following an Institute of Medicine-compliant process to ensure transparency and patient engagement. Recommendations were supported by structured rationales, integrating evidence from the systematic review, related evidence, principles of care, and inferences from evidence. Initial treatment with levodopa provides superior motor benefit compared to treatment with dopamine agonists, whereas levodopa is more likely than dopamine agonists to cause dyskinesia. The comparison of different formulations of dopamine agonists yielded little evidence that any one formulation or method of administration is superior. Long-acting forms of levodopa and levodopa with entacapone do not appear to differ in efficacy from immediate-release levodopa for motor symptoms in early disease. There is a higher risk of impulse control disorders associated with the use of dopamine agonists than levodopa. Recommendations on initial therapy for motor symptoms are provided to assist the clinician and patient in choosing between treatment options and to guide counseling, prescribing, and monitoring of efficacy and safety.

Aripiprazole as a risk factor for impulse control disorders: a systematic review

AimsAripiprazole is an anti-psychotic medication widely used for bipolar affective disorder and depression. It's primary mechanism of action is as a partial dopamine agonist. Aripiprazole's effect on dopamine signalling in the mesolimbic and mesocortical pathways may lead to impulse control disorders, as seen with other dopamine agonist medications. Aripiprazole is often chosen by prescribers because of its favourable side effect profile. There is a need to synthesise the available epidemiological literature on the potential association between aripiprazole use and impulse control disorders. This is needed to inform patients and prescribers of the best available evidence regarding this potential association. Our aim is to conduct a systematic review of the available non case-study evidence on the potential association between aripiprazole and impulse control disorders.MethodDatabases were searched using MEDLINE, PsychINFO, EMBASE, Cochrane Clinical Trials and Web of science. All studies from no earliest date to December 2020 were included; adult patients with a severe and enduring mental illness prescribed antipsychotic medication were included. Cinician diagnosis, structured interview diagnosis, and interviewer or self-completion questionnaires were used to measure prevalence. The study designs included were experimental designs, cohort study, cross-sectional survey and administrative databases. Exclusion criteria being those with traumatic brain injury, psychosis secondary to autoimmune, iatrogenic, chromosomal or metabolic disorder, those with Learning disability or Autistic Spectrum disorders. studies with majority of participants <18yrs. Those who were on other antipsychotic medications in addition to Aripiprazole, were excluded. To ensure quality assurance, we used ROBINS-I tool and GRADE assessment to measure the risk of bias.Result240 records were retrieved, 187 after duplicates were removed. 8 full text articles were assessed for eligibility, of which 4 were included in the qualitative synthesis. 2 studies were analyses of spontaneous adverse drug reaction reporting systems and 2 of health insurance claims databases. All 4 studies found aripiprazole to be associated with greater risk of impulse control disorders. The single study which compared directly with other antipsychotics had a much smaller effect size. Study heterogeneity precluded meta-analysis. All studies were at high risk of bias. The quality of evidence is very low.ConclusionThe available evidence is consistent with the existing warnings regarding increased risk of impulse control disorders in patients prescribed aripiprazole. Clinicians may wish to monitor for this adverse drug reaction. Further research which can account for potential confounders, examines specific impulse control disorders and which is less susceptible to detection and ascertainment biases is required.

Impulse Control Disorders in Parkinson's Disease: From Bench to Bedside.

Parkinson’s disease (PD) is a neurodegenerative disorder that is characterized by symptoms that impact both motor and non-motor domains. Outside of motor impairments, PD patients are at risk for impulse control disorders (ICDs), which include excessively disabling impulsive and compulsive behaviors. ICD symptoms in PD (PD + ICD) can be broadly conceptualized as a synergistic interaction between dopamine agonist therapy and the many molecular and circuit-level changes intrinsic to PD. Aside from discontinuing dopamine agonist treatment, there remains a lack of consensus on how to best address ICD symptoms in PD. In this review, we explore recent advances in the molecular and neuroanatomical mechanisms underlying ICD symptoms in PD by summarizing a rapidly accumulating body of clinical and preclinical studies, with a special focus on the utility of rodent models in gaining new insights into the neurochemical basis of PD + ICD. We also discuss the relevance of these findings to the broader problem of impulsive and compulsive behaviors that impact a range of neuropsychiatric syndromes.

Apomorphine: a powerful ally in Parkinson's disease

Apomorphine, a D1-D2 dopamine agonist, is the oldest drug with proven efficacy in the treatment of Parkinson's disease (PD), and the only with similar symptomatic power to levodopa. Its usefulness in the control of motor fluctuations, both as intermittent injections and in continuous subcutaneous infusion, has been demonstrated in open label and placebo controlled trials. To analyse the role of apomorphine in the varied clinical symptoms and different clinical stages of PD through a narrative review of scientific literature (1951-2020). Beyond on-time increase, off-time decrease, off dystonia and quality of life improvement in advanced PD, there is evidence to support a role of apomorphine in less known clinical areas of PD, such as non motor symptoms, a lower risk of impulse control disorders, potential to ameliorate visual hallucinations, improve neuropsychiatric symptoms and dyskinesia and even axial features. Nevertheless, the optimal timing of apomorphine treatment remains controversial, and its implementation of this valuable drug in clinical practice has been historically hindered by several factors. Apomorphine is a unique drug in the PD treatment scenario, with a number of potential applications beyond motor fluctuations control. Acknowledging these properties, selecting the patient most likely to benefit from it and finding the right timing may be key in the symptomatic control of this complex disease.

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

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. We included 353 patients with PD in this study (58.9% men, mean age 62.4±10.58years, mean age at disease onset 52.71±11.94years). 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. 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. 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.

Medical management after subthalamic stimulation in Parkinson's disease: a phenotype perspective.

Subthalamic nucleus deep brain stimulation (STN DBS) is an established treatment that improves motor fluctuations, dyskinesia, and tremor in Parkinson's disease (PD). After the surgery, a careful electrode programming strategy and medical management are crucial, because an imbalance between them can compromise the quality of life over time. Clinical management is not straightforward and depends on several perioperative motor and non-motor symptoms. In this study, we review the literature data on acute medical management after STN DBS in PD and propose a clinical algorithm on medical management focused on the patient's phenotypic profile at the perioperative period. Overall, across the trials, the levodopa equivalent daily dose is reduced by 30 to 50% one year after surgery. In patients taking high doses of dopaminergic drugs or with high risk of impulse control disorders, an initial reduction in dopamine agonists after STN DBS is recommended to avoid the hyperdopaminergic syndrome, particularly hypomania. On the other hand, a rapid reduction of dopaminergic agonists of more than 70% during the first months can lead to dopaminergic agonist withdrawal syndrome, characterized by apathy, pain, and autonomic features. In a subset of patients with severe dyskinesia before surgery, an initial reduction in levodopa seems to be a more reasonable approach. Finally, when the patient's phenotype before the surgery is the severe parkinsonism (wearing-off) with or without tremor, reduction of the medication after surgery can be more conservative. Individualized medical management following DBS contributes to the ultimate therapy success.

Gender Differences in Impulse Control Disorders and Related Behaviors in Patients with Parkinson's Disease and its Impact on Quality of Life.

Background:Dopaminergic medications administered to remedy motor symptoms in Parkinson’s disease are associated with an enhanced risk for impulse control disorders (ICD) and related compulsive behaviors (ICD-RB). Thus, the present study focuses on investigating the gender difference in the prevalence of ICD-RBs in Indian PD patients on dopamine replacement therapy (DRT), its impact on quality of life and to identify ICDs relevant in Indian scenario apart from the criteria set in QUIP-RS.Method:This was a hospital-based observational cross-sectional study in which Parkinson’s disease patients attending neurology clinic were included. Complete details of anti-parkinsonian therapy along with demographic and clinical variables were recorded on a predesigned Performa. Questionnaire for Impulsive-Compulsive Disorders in Parkinson’s disease (QUIP), which is a validated quick screening tool, was used to detect ICD-RBs. The relative frequency and comparative impact of ICD on health-related quality of life (QOL) was studied using validated PDQ-39 Questionnaire.Results:Out of 102 patients, at least one ICD or ICD-RB was present in 41.19% and ≥2 ICD-RBs were present in 15.59%. At least one ICD was present in 16.67%, any ICD-related compulsive behaviors was present in 34.31% patients. The most common was punding and compulsive medication use (12.75% each), followed by hobbyism (7.84%), compulsive eating (6.86%), pathological gambling (3.92%), and hypersexuality, walkabout, and compulsive shopping (2.94% each). ICDs not classified elsewhere such as trichotillomania were found 3 patients (2.94%). ICD-RBs showed a trend to be more frequent in women (44.82% women vs. 39.39% men). As compared with patients without ICD-RBs, those with ICD-RBs were found to have higher dose of LD and DA and higher Hoehn and Yahr stage. ICD-RBs have a negative impact on the quality of life of Parkinson’s disease patients.Conclusion:ICDs and ICD-RBs have been included in the behavioral spectrum of nonmotor symptoms in PD. PD patients are at increased risk of developing ICD-RBs which interfere with important activities and have obligation in ordinary life, leading to legal and psychological consequences with a great impact on QOL.

Impulse control symptoms in patients with Parkinson's disease: The influence of dopaminergic agonist

BackgroundImpulse control disorders and punding are common in Parkinson's disease patients. Cross-sectional studies suggest an association between dopamine replacement therapy, especially dopaminergic agonists, and impulse control and related disorders in Parkinson's disease. However, some surveys suggest that Parkinson's disease itself does not confer an altered risk for impulse control disorders and related behavior, although these disturbances are more frequently reported in Parkinsonian patients than in healthy controls. ObjectiveTo ascertain the frequency of impulse control disorders and punding symptoms in Parkinson's disease patients and healthy controls and to determine the influence of dopamine agonist treatment on the prevalence of these disturbances. MethodsA case-control study was conducted on 207 Parkinson's disease patients (79 taking dopamine agonists) and 230 healthy controls. The outcome measures were the presence of current impulse control disorders and punding symptoms, based on clinical criteria after application of the Minnesota Impulsive Disorders Interview for screening. ResultsThe frequency of impulse control disorders in Parkinson's disease patients vs. Healthy controls was 16.9% vs. 15.2% (p = 0.631). Punding was more frequent in Parkinson's disease patients (p = 0.028); however, impulse control disorders were more frequent in medicated Parkinson's disease patients taking dopamine agonists than in medicated patients not taking dopamine agonists (p = 0.001) and healthy controls (p = 0.014). ConclusionsParkinson's disease itself does not lead to the development of impulse control disorders. Dopaminergic agonist treatment may trigger the disorder in susceptible individuals. Punding may be more prevalent in Parkinson's disease patients.

Medications, Deep Brain Stimulation, and Other Factors Influencing Impulse Control Disorders in Parkinson's Disease.

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.

White Matter Tract Alterations in Drug-Naïve Parkinson's Disease Patients With Impulse Control Disorders.

Impulse control disorders (ICDs) are relatively frequent in patients with Parkinson’s disease (PD), although it is still unclear whether an underlying pathological process plays a significant role in the development of ICD in PD apart from dopaminergic replacement therapy. In this study, we have investigated alterations of white matter tract in drug-naïve PD patients with ICDs via diffusion MRI connectometry. Our results showed that disrupted connectivity in the complex network of dynamic connections between cerebellum, basal ganglia, cortex, and its spinal projections serves as the underlying neuropathology of ICD in PD not interfered with the contribution of dopaminergic replacement therapy. These findings provide the first evidence on involved white matter tracts in the neuropathogenesis of ICD in drug-naïve PD population, supporting the hypothesis that neural disturbances intrinsic to PD may confer an increased risk for ICDs. Future studies are needed to validate the attribution of the impaired corticocerebellar network to impulsivity in PD.

Dopaminergic and Opioid Pathways Associated with Impulse Control Disorders in Parkinson's Disease.

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. 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. 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. 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.

Risky decision-making and affective features of impulse control disorders in Parkinson\u2019s disease

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.

Higher risk of impulse control disorders with dopamine agonists

Higher risk of impulse control disorders with dopamine agonists