Impulse Control Symptoms Research Articles

Neural Reinforcement Learning Signals Predict Recovery From Impulse Control Disorder Symptoms in Parkinson’s Disease

BackgroundImpulse control disorders (ICDs) in Parkinson’s disease are associated with a heavy burden on patients and caretakers. While recovery can occur, ICDs persist in many patients despite optimal management. The basis for this interindividual variability in recovery is unclear and poses a major challenge to personalized health care. MethodsWe adopted a computational psychiatry approach and leveraged the longitudinal, prospective Personalized Parkinson Project (136 people with Parkinson’s disease, within 5 years of diagnosis) to combine dopaminergic learning theory–informed functional magnetic resonance imaging with machine learning (at baseline) to predict ICD symptom recovery after 2 years of follow-up. We focused on change in Questionnaire for Impulsive-Compulsive Disorders in Parkinson’s Disease Rating Scale scores in the entire sample regardless of an ICD diagnosis. ResultsGreater reinforcement learning signals during gain trials but not loss trials at baseline, including those in the ventral striatum and medial prefrontal cortex, and the behavioral accuracy score measured while on medication were associated with greater recovery from impulse control symptoms 2 years later. These signals accounted for a unique proportion of the relevant variability over and above that explained by other known factors, such as decreases in dopamine agonist use. ConclusionsOur results provide a proof of principle for combining generative model–based inference of latent learning processes with machine learning–based predictive modeling of variability in clinical symptom recovery trajectories. We showed that reinforcement learning modeling parameters predicted recovery from ICD symptoms in Parkinson’s disease.

Hypersexuality during treatment with cariprazine in a patient with schizophrenia? A case report

BackgroundCariprazine is a third-generation antipsychotic with a unique mechanism of action. It functions as a partial agonist with high affinity for dopamine D2 and D3 and serotonin 5-HT1A receptors, an antagonist for 5-HT2A (moderate affinity) and 5-HT2B (high affinity) receptors. It binds to histamine H1 receptors and has a low affinity for 5-HT2C and alpha 1A-adrenergic receptors and no affinity for muscarinic (cholinergic) receptors. Among the troubling side effects, symptoms related to impulse control, such as hypersexuality, pathological gambling, compulsive shopping, compulsive eating etc., have been reported with the use of antipsychotic medications. However, no reports have been published regarding impulse control symptoms associated with cariprazine. We report a case of cariprazine-induced hypersexuality in a patient with schizophrenia, which was resolved by discontinuation of the medication.Case presentationA 67-year-old Caucasian woman with schizophrenia was admitted to the hospital inpatient unit after she discontinued olanzapine and psychotic symptoms reappeared. Prior to that, she was in remission, taking olanzapine for approximately one year. After discontinuation, she experienced auditory hallucinations with persecutory delusions and became anergic and withdrawn, with blunted affect. Olanzapine was reintroduced, as it was proven successful in her past treatments. However, since there were no changes, especially in negative symptoms, cariprazine was added. Seven days after the introduction of cariprazine, the patient developed compulsive sexual behaviour. Therefore, cariprazine was discontinued, and the hypersexual behaviour was resolved.ConclusionsIn this case report, we describe hypersexual behaviour that could potentially be induced by cariprazine. As a single case study, conclusions cannot be drawn. Controlled studies are warranted to better determine causality and the significance of this possible side-effect of cariprazine.

0123 Sleep Problems and Externalizing Behaviors for Youth in Juvenile Justice Facilities

Abstract Introduction Adolescents who experience insufficient, poor quality sleep, and sleep problems might experience difficulties with externalizing behaviors including aggression and impulse control (Bauducco et al., 2019; Brown et al., 2022). Surprisingly, sleep and behavior for youth residing in long and short-term juvenile justice facilities is understudied. The present preliminary analysis explores self-reported sleep problems and aggressive and impulse control symptoms for youth under the care of the Department of Juvenile Services (DJS). Methods Participants (N=62, 86% male, mean age = 16.8, SD=1.2) were recruited from 11 DJS detention and treatment facilities in Maryland. Racial Backgrounds: 55% Black, 18% White, 14% Multiracial, and 12% Other. They completed an online questionnaire focused on sleep behaviors (daytime sleepiness, sleep-wake behavior problems) and daytime functioning including aggressive and impulse control behaviors (e.g., modified Aggression Questionnaire, Buss & Perry, 1992; Weinberger Adjustment Inventory, WAI, 1990). Using Pearson correlations, associations between sleep problems, daytime sleepiness and externalizing behaviors were examined. Results Self-reported daytime sleepiness and sleep-wake behavior problems were associated with increased aggressive and impulse control difficulties. Youth with more sleep-wake behavior problems reported higher levels of aggressive behaviors (r = .39, p < .01) and impulse control behaviors as measured by the WAI (r = .33, p < .05). Similarly, youth with high levels of daytime sleepiness also reported more impulse control behaviors (r = .40, p < .01). Conclusion Preliminary findings suggest that youth residing in juvenile justice facilities with sleep difficulties are more likely to report aggressive and impulse control challenges. Further analyses will provide a greater understanding of the modifying factors to better understand the youth’s sleep-living environment. Support (if any) This research is made possible by the American Academy of Sleep Medicine (AASM) Foundation Award #22-CS-19 and Maryland Department of Juvenile Services’ supportive collaboration.

Association of locus coeruleus integrity with Braak stage and neuropsychiatric symptom severity in Alzheimer's disease.

The clinical and pathophysiological correlates of locus coeruleus (LC) degeneration in Alzheimer's disease (AD) could be clarified using a method to index LC integrity in vivo, neuromelanin-sensitive MRI (NM-MRI). We examined whether integrity of the LC-norepinephrine system, assessed with NM-MRI, is associated with stage of AD and with neuropsychiatric symptoms (NPS), independent of cortical pathophysiology (amyloid-β and tau burden). Cognitively normal older adults (n = 118), and individuals with mild cognitive impairment (MCI, n = 44), and AD (n = 28) underwent MR imaging and tau and amyloid-β positron emission tomography (with [18F]MK6240 and [18F]AZD4694, respectively). Integrity of the LC-norepinephrine system was assessed based on contrast-to-noise ratio of the LC on NM-MRI images. Braak stage of AD was derived from regional binding of [18F]MK6240. NPS were assessed with the Mild Behavioral Impairment Checklist (MBI-C). LC signal contrast was decreased in tau-positive participants (t186 = -4.00, p = 0.0001) and negatively correlated to Braak stage (Spearman ρ = -0.31, p = 0.00006). In tau-positive participants (n = 51), higher LC signal predicted NPS severity (ρ = 0.35, p = 0.019) independently of tau burden, amyloid-β burden, and cortical gray matter volume. This relationship appeared to be driven by the impulse dyscontrol domain of NPS, which was highly correlated to LC signal (ρ = 0.44, p = 0.0027). NM-MRI reveals loss of LC integrity that correlates to severity of AD. However, LC preservation in AD may also have negative consequences by conferring risk for impulse control symptoms. NM-MRI shows promise as a practical biomarker that could have utility in predicting the risk of NPS or guiding their treatment in AD.

Do cariprazine and brexpiprazole cause impulse control symptoms? A case/non-case study

Aripiprazole has been associated with impulse control symptoms (ICS). Recently, two drugs with similar pharmacological features have become available: cariprazine and brexpiprazole. All of them interact with the D3 receptor, which plays a role in cerebral circuits involved in reward pathways. The objective of this study was to analyze whether a disproportionate number of cases of ICS are reported for cariprazine or brexpiprazole in EudraVigilance. A case/non-case study was conducted to assess the association between ICS and these antipsychotics, calculating reporting odds ratios (RORs) from their respective approval date to Nov 17, 2020. First, cases involving cariprazine or brexpiprazole were compared with those involving all other drugs. Second, to reduce the risk of confounding by indication, the RORs for cariprazine and brexpiprazole were compared with other antipsychotics. Besides, to evaluate a possible notoriety bias, a sensitivity analysis excluding aripiprazole was performed. Seven cases of ICS were reported for cariprazine and another seven for brexpiprazole. The ROR for cariprazine was 28.3 (95% confidence interval [CI], 13.4–59.8) and 33.4 (15.8–70.1) in the case of brexpiprazole. Nonetheless, this association disappeared for cariprazine when compared with other antipsychotics drugs. However, when excluding aripiprazole from the analysis, a safety signal emerged. Although our study is the first to suggest an association between cariprazine, brexpiprazole and ICS, these results should only be considered as exploratory in the context of safety signal detection. Further, well designed observational analytical studies will be needed to confirm these results.

Dopamine agonist treatment increases sensitivity to gamble outcomes in the hippocampus in de novo Parkinson’s disease

BackgroundParkinson’s disease is associated with severe nigro-striatal dopamine depletion, leading to motor dysfunction and altered reward processing. We previously showed that drug-naïve patients with Parkinson’s disease had a consistent attenuation of reward signalling in the mesolimbic and mesocortical system. Here, we address the neurobiological effects of dopaminergic therapy on reward sensitivity in the mesolimbic circuitry, and how this may contribute to neuropsychiatric symptoms. ObjectivesWe tested the hypothesis that (1) dopaminergic treatment would restore the attenuated, mesolimbic and mesocortical responses to reward; and (2) restoration of reward responsivity by dopaminergic treatment would predict motor performance and the emergence of impulse control symptoms. MethodsIn 11 drug-naïve Parkinson patients, we prospectively assessed treatment-induced changes in reward processing before, and eight weeks after initiation of monotherapy with dopamine agonists. They were compared to 10 non-medicated healthy controls who were also measured longitudinally. We used whole-brain functional magnetic resonance imaging at 3 Tesla to assess the reward responsivity of the brain to monetary gains and losses, while participants performed a simple consequential gambling task. ResultsIn patients, dopaminergic treatment improved clinical motor symptoms without significantly changing task performance. Dopamine agonist therapy induced a stronger reward responsivity in the right hippocampus with higher doses being less effective. None of the patients developed impulse control disorders in the follow-up period of four years. ConclusionsShort-term treatment with first-ever dopaminergic medication partially restores deficient reward-related processing in the hippocampus in de novo Parkinson’s disease.

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.

Use of Antipsychotic Drugs for Psychotic Disorders in Children

This review aims to provide evidence-based guidance regarding the use of antipsychotic medications for treatment of children and adolescents with psychotic disorders. Research findings from the past 3 years are emphasized. A number of studies have demonstrated the efficacy of antipsychotic medications for use in children and/or adolescents with psychotic disorders, but there is also high potential for significant side effects. Atypical antipsychotic drugs are often preferred instead of typical antipsychotics due to reduced risk of extrapyramidal symptoms, but the risk for weight gain and metabolic side effects is a particular concern with atypical antipsychotic drugs. Several antipsychotics are now FDA approved for the treatment of schizophrenia in the pediatric population, including the atypical antipsychotics aripiprazole, lurasidone, olanzapine, paliperidone, quetiapine, and risperidone. Although clozapine is not FDA approved for use in the pediatric population, and children may be more susceptible to serious side effects from this medication, studies have demonstrated its efficacy in treating early-onset schizophrenia. A recently reported rare but potentially serious side effect of the third-generation antipsychotic aripiprazole is new-onset impulse control symptoms (such as compulsive gambling and sexual urges), but there is not enough information available to show whether this particular adverse event is as common in children as in adults. Although the use of antipsychotic drugs is appropriate to control symptoms of early-onset primary psychotic disorders, the potential for medically significant side effects from these drugs warrants a need for careful diagnostic evaluation prior to starting antipsychotics in children, followed by careful monitoring and management of adverse events that may occur during treatment. Further research is needed to determine the relative efficacy of treatment options, investigate the value of polypharmacy, and develop methods of preventing and managing adverse effects.

Increased risk of impulse control symptoms in Parkinson's disease with REM sleep behaviour disorder

ObjectiveTo assess the frequency of symptoms of impulse control disorders (ICD, namely pathological gambling, compulsive sexual behaviour, compulsive eating and compulsive shopping) and related behaviours (hobbyism, punding, walkabout and dopamine...

REM sleep behavior disorder is associated to increased risk of impulse control symptoms in patients with Parkinson’s disease

REM sleep behavior disorder (RBD) affects about 50% of patients with Parkinson’s disease (PD) and is often associated to more severe both motor and non-motor impairment.However, it is unknown whether PD-RBD patients have an increased risk to develop impulse control disorders (ICDs) compared to PD-noRBD. We aimed to assess the frequency of ICD and related behaviors symptoms in PD with and without probable RBD. Two hundred and twenty consecutive patients with idiopathic PD (132 M, mean age: 66.6 ± 11.0 yrs.; mean duration of PD: 7.3 ± 4.7 yrs.; mean Hoen and Yahr score: 1.9 ± 0.7, mean Levo-dopa Equivalent Daily Dose: 731.8 ± 448.6 mg) filled out the RBD-Single question, the RBD Screening Questionnaire (RBDSQ) and the Questionnaire for Impulsive-Compulsive Disorders in Parkinson’s Disease’s (QUIP). Probable RBD was found in 99/220 (45%, 59 M) patients.One or more ICDs or related behaviors were found in 60/99 (60.6%) patients with PD-pRBD and in 46/121 (38.0%) PD-noRBD ( p = 0.001).PD-pRBD showed a higher QUIP score (1.5 ± 1.7 vs.0.8 ± 1.3; p = 0.009) and a higher number of ICD and related behaviors symptoms (1.5 ± 1.7 vs.0.9 ± 1.3; p = 0.001) compared to PD-noRBD. Furthermore, a significant positive correlation between RBDSQ and QUIP scores was observed in the whole group ( R = 0.269; p < 0.001).The frequencies of ICD symptoms in patients with PD-pRBD compared to PD-noRBD were as follows: compulsive gambling (9.1% vs.3.3%; p = 0.07), compulsive sexual behaviors (11.1%vs.6.6%; p = 0.23) compulsive shopping (14.4% vs.4.1%, p = 0.008) compulsive eating (18.2% vs.14.0%, p = 0.39), hobbyism (24.2% vs.13.2, p = 0.03), punding (19.2% vs.10.7%, p = 0.09), walkabout (6.1% vs.7.4%, p = 0.67), dopamine dysregulation syndrome (18.2% vs.5.0%, p = 0.002).A logistic regression model accounting for Center (Clermont-Ferrand/Turin), sex, age, PD duration, PD severity (H&Y score) and Levo-Dopa Equivalent Daily Dose, indicated that PD- pRBD have a twofold risk to develop any ICDs (RR: 2.1 (C.I. 1.31–3.60); p = 0.003) and a threefold risk to develop compulsive shopping (RR: 3.15 (1.11–8.9); p = 0.03 and Dopamine Dysregulation syndrome (RR: 3.15 (1.23–8.079; p = 0.017) compared to PD patients without RBD. This study showed for the first time that RBD is associated to an increased risk to develop ICD symptoms in PD, even after controlling for age, severity, duration of PD and dopaminergic treatment. Further studies are warranted to clarify the mechanism underlying this association. Authors are in debt with neuropsychologist Dr. Tiphaine Vidal and neurologists Drs. Ana-Raquel Marques, Bérangère Debilly, Philippe Derost, Miguel Ulla and Nicolas Vitello for their contribution in collecting clinical data and with biostatistician Bruno Pereira for helping in statistical analysis.

Screening for impulse control symptoms in patients with de novo Parkinson disease: A case-control study

Editors’ Note: In this week’s Writ e Click, O’Callaghan and Hornberger point out that there are studies that contradict the findings of authors Weintraub et al. that dopaminergic therapy in Parkinson disease (PD) is the driver behind impulse control disorders rather than the disease itself. They suggest a compromise theory and more objective screening. The authors disagree on both points. Megan Alcauskas, MD, and Robert C. Griggs, MD # {#article-title-2} Weintraub et al.1 found that de novo PD itself does not confer an increased risk for impulse control disorders (ICDs). This implies that dopaminergic …

Screening for impulse control symptoms in patients with de novo Parkinson disease

To determine the frequency and correlates of impulse control and related behavior symptoms in patients with de novo, untreated Parkinson disease (PD) and healthy controls (HCs). The Parkinson's Progression Markers Initiative is an international, multisite, case-control clinical study conducted at 21 academic movement disorders centers. Participants were recently diagnosed, untreated PD patients (n = 168) and HCs (n = 143). The outcome measures were presence of current impulse control and related behavior symptoms based on recommended cutoff points for the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease (QUIP)-Short Form. There were 311 participants with complete QUIP data. Frequencies of impulse control and related behavior symptoms for patients with PD vs HCs were as follows: gambling (1.2% vs. 0.7%), buying (3.0% vs. 2.1%), sexual behavior (4.2% vs. 3.5%), eating (7.1% vs. 10.5%), punding (4.8% vs. 2.1%), hobbyism (5.4% vs. 11.9%), walkabout (0.6% vs. 0.7%), and any impulse control or related behavior (18.5% vs. 20.3%). In multivariable models, a diagnosis of PD was not associated with symptoms of any impulse control or related behavior (p ≥ 0.10 in all cases). PD itself does not seem to confer an increased risk for development of impulse control or related behavior symptoms, which further reinforces the reported association between PD medications and impulse control disorders in PD. Given that approximately 20% of patients with newly diagnosed PD report some impulse control or related behavior symptoms, long-term follow-up is needed to determine whether such patients are at increased risk for impulse control disorder development once PD medications are initiated.

Demand‐specific alteration of medial prefrontal cortex response during an inhibition task in recovered anorexic women

It is well known that individuals with anorexia nervosa (AN) are inhibited and over-controlled. This study investigated a prefrontal-cingulate network that is involved in inhibitory control. To avoid the confounds of malnutrition, 12 recovered (RAN) subjects were compared to 12 matched control women (CW) using a validated inhibition task (i.e., a stop signal task) during functional magnetic resonance imaging. Consistent with the a priori hypothesis, RAN subjects showed altered task-related activation in the medial prefrontal cortex (mPFC), a critical node of the inhibitory control network. Specifically, whereas RAN and CW showed similar mPFC activity during trials when inhibitory demand was low (i.e., easy trials), RAN relative to CW showed significantly less mPFC activation as inhibition trials became more difficult (i.e., hard trials), suggesting a demand-specific modulation of inhibitory control circuitry in RAN. These findings support a neural basis for altered impulse control symptoms in AN.