Impulse control disorder in Parkinson's disease is associated with abnormal frontal value signalling.

Dopaminergic medication is well established to boost reward- versus punishment-based learning in Parkinson's disease. However, there is tremendous variability in dopaminergic medication effects across different individuals, with some patients exhibiting much greater cognitive sensitivity to medication than others. We aimed to unravel the mechanisms underlying this individual variability in a large heterogeneous sample of early-stage patients with Parkinson's disease as a function of comorbid neuropsychiatric symptomatology, in particular impulse control disorders and depression. One hundred and ninety-nine patients with Parkinson's disease (138 ON medication and 61 OFF medication) and 59 healthy controls were scanned with functional MRI while they performed an established probabilistic instrumental learning task. Reinforcement learning model-based analyses revealed medication group differences in learning from gains versus losses, but only in patients with impulse control disorders. Furthermore, expected-value related brain signalling in the ventromedial prefrontal cortex was increased in patients with impulse control disorders ON medication compared with those OFF medication, while striatal reward prediction error signalling remained unaltered. These data substantiate the hypothesis that dopamine's effects on reinforcement learning in Parkinson's disease vary with individual differences in comorbid impulse control disorder and suggest they reflect deficient computation of value in medial frontal cortex, rather than deficient reward prediction error signalling in striatum. See Michael Browning (https://doi.org/10.1093/brain/awad248) for a scientific commentary on this article.

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.

Disrupted reward processing in Parkinson's disease and its relationship with dopamine state and neuropsychiatric syndromes: a systematic review and meta-analysis.

BACKGROUND: Neuropsychiatric symptoms are common in Parkinson's disease (PD) and predict poorer outcomes. Reward processing dysfunction is a candidate mechanism for the development of psychiatric symptoms including depression and impulse control disorders (ICDs). We aimed to determine whether reward processing is impaired in PD and its relationship with neuropsychiatric syndromes and dopamine replacement therapy. METHODS: The Ovid MEDLINE/PubMed, Embase and PsycInfo databases were searched for articles published up to 5 November 2020. Studies reporting reward processing task performance by patients with PD and healthy controls were included. Summary statistics comparing reward processing between groups were converted to standardised mean difference (SMD) scores and meta-analysed using a random effects model. RESULTS: We identified 55 studies containing 2578 participants (1638 PD and 940 healthy controls). Studies assessing three subcomponent categories of reward processing tasks were included: option valuation (n=12), reinforcement learning (n=37) and reward response vigour (n=6). Across all studies, patients with PD on medication exhibited a small-to-medium impairment versus healthy controls (SMD=0.34; 95% CI 0.14 to 0.53), with greater impairments observed off dopaminergic medication in within-subjects designs (SMD=0.43, 95% CI 0.29 to 0.57). Within-subjects subcomponent analysis revealed impaired processing off medication on option valuation (SMD=0.57, 95% CI 0.39 to 0.75) and reward response vigour (SMD=0.36, 95% CI 0.13 to 0.59) tasks. However, the opposite applied for reinforcement learning, which relative to healthy controls was impaired on-medication (SMD=0.45, 95% CI 0.25 to 0.65) but not off-medication (SMD=0.28, 95% CI -0.03 to 0.59). ICD was the only neuropsychiatric syndrome with sufficient studies (n=13) for meta-analysis, but no significant impairment was identified compared tonon-ICD patients (SMD=-0.02, 95% CI -0.43 to 0.39). CONCLUSION: Reward processing disruption in PD differs according to subcomponent and dopamine medication state, and warrants further study as a potential treatment target and mechanism underlying associated neuropsychiatric syndromes.

Factors associated with augmentation in patients with restless legs syndrome.

BACKGROUND AND PURPOSE: Augmentation is a paradoxical reaction mainly to dopaminergic medication in patients with restless legs syndrome (RLS), but the exact pathomechanism remains unclear. The aim of this study was to identify factors associated with augmentation in RLS patients. METHODS: RLS patients with and without current or previous augmentation were recruited. Demographic characteristics, history of smoking, questionnaires for depression, alexithymia, and impulsivity, and RLS severity were obtained. RESULTS: We included 122 patients, of whom half had a history of augmentation. Patients with augmentation had a longer disease duration (p = 0.001), had higher RLS severity scores (p = 0.013), had higher levodopa equivalent doses (p < 0.001), had higher scores for alexithymia (p = 0.028), had higher prevalence of impulse control disorders (p < 0.001), more often had a history of smoking (p = 0.039), were more often currently smoking (p = 0.015), and had more average pack-years (p = 0.016). CONCLUSIONS: Here, we describe several factors commonly associated with augmentation in RLS. These may help clinicians to screen and treat patients carefully to avoid the challenging side effect of augmentation.

Neural correlates of risky decision making in Parkinson's disease patients with impulse control disorders.

Some patients with Parkinson's disease (PD) experience impulse control disorders (ICDs), characterized by deficient voluntary control over impulses, drives, or temptations regarding excessive hedonic behavior. The present study aimed to better understand the neural basis of impulsive, risky decision making in PD patients with ICDs by disentangling potential dysfunctions in decision and outcome mechanisms. We collected fMRI data from 20 patients with ICDs and 28 without ICDs performing an information gathering task. Patients viewed sequences of bead colors drawn from hidden urns and were instructed to infer the majority bead color in each urn. With each new bead, they could choose to either seek more evidence by drawing another bead (draw choice) or make an urn-inference (urn choice followed by feedback). We manipulated risk via the probability of bead color splits (80/20 vs. 60/40) and potential loss following an incorrect inference ($10 vs. $0). Patients also completed the Barratt Impulsiveness Scale (BIS) to assess impulsivity. Patients with ICDs showed greater urn choice-specific activation in the right middle frontal gyrus, overlapping the dorsal premotor cortex. Across all patients, fewer draw choices (i.e., more impulsivity) were associated with greater activation during both decision making and outcome processing in a variety of frontal and parietal areas, cerebellum, and bilateral striatum. Our findings demonstrate that ICDs in PD are associated with differences in neural processing of risk-related information and outcomes, implicating both reward and sensorimotor dopaminergic pathways.

The urge to move: From restless legs syndrome to impulse control disorders in Parkinson's disease.

Impulse control disorders (ICDs) in Parkinson's disease (PD) are defined as a failure to resist an "urge" to behave in a way that may be debilitating for oneself or others. The suggested immobilization test (SIT) has been developed to assess the "urge" to move and support the diagnosis of restless legs syndrome (RLS) in the general population and in PD. A clinical association between RLS and ICDs has been shown in PD and in the general population. We hypothesized that there could be a semiological overlap between RLS and ICDs, and conducted SIT in PD patients with and without ICDs. Fifty PD patients with (n = 17) and without (n = 33) current ICDs were included. SIT, videopolysomnography, demographical treatment, and motor, psycho-behavioural and sleep characteristics, including RLS, were recorded. PD patients with ICDs reported increased subjective discomfort during SIT (SD-SIT) compared to those without ICDs (p = .024). Multivariable analysis confirmed ICDs as an independent factor associated with increased SD-SIT in PD, regardless of the presence of RLS, PD severity and dopamine agonist treatment dose. The discomfort measured by SIT might not only reflect the "urge" to move in RLS but also the ICDs in PD, suggesting that ICDs and RLS in PD could share a common phenomenology.

Spectrum of impulse control behaviours in Parkinson's disease: pathophysiology and management.

Impulse control behaviours (ICBs) are a range of behaviours linked by their reward-based, repetitive natures. They can be precipitated in Parkinson's disease (PD) by dopamine replacement therapy, often with detrimental consequences for patients and caregivers. While now a well-recognised non-motor feature of treated PD, much remains unknown about the influence of risk factors, pathophysiological mechanisms, vulnerability factors for specific types of behaviour and the optimal management strategies. Imaging studies have identified structural and functional changes in striatal and prefrontal brain regions, among others. Gene association studies indicate a role for genetic predisposition to PD-ICB. Clinical observational studies have identified potential modifiable and non-modifiable risk factors. Psychological studies shed light on the neurocognitive domains implicated in PD-ICBs and identify psychosocial determinants that may perpetuate the cycle of impulsive and harm-avoidance behaviours. Based on these results, a range of pharmacological and non-pharmacological management strategies have been trialled in PD-ICBs with varying success. The purpose of this review is to update clinicians on the evidence around the pathophysiology of PD-ICB. We aim to translate our findings into an interpretable biopsychosocial model that can be applied to the clinical assessment and management of individual cases of PD-ICB.

Cross-sectional and longitudinal associations between probable rapid eye movement sleep behavior disorder and impulse control disorders in Parkinson's disease.

BACKGROUND AND PURPOSE: The aim was to investigate whether probable rapid eye movement sleep behavior disorder (pRBD) is associated with impulse control disorders (ICDs) in drug-naïve patients with Parkinson's disease (PD) and whether baseline pRBD is associated with a higher incidence of ICDs during follow-up. METHODS: The Parkinson's Progression Markers Initiative is an international, multicenter, prospective cohort study to identify biomarkers of PD progression. In all, 423 drug-naïve patients with early-stage PD were included in the cross-sectional analysis, and 320 patients who screened negative for any ICDs or related behaviors at baseline were included in the longitudinal analysis. RESULTS: In the cross-sectional analysis, a significant correlation was found between pRBD and ICDs in drug-naïve patients whilst controlling for potential confounders [odds ratio 2.56, 95% confidence interval (CI) 1.38-4.76, P = 0.003]. In the longitudinal analysis, baseline pRBD was an independent predictor of ICD development over time [hazard ratio (HR) 1.648, 95% CI 1.054-2.576; P = 0.028]. Other significant predictors of ICDs included younger age of onset (HR = 0.973, 95% CI = 0.950-0.997; P = 0.026) and greater State-Trait Anxiety Inventory score (HR = 1.040, 95% CI = 1.020-1.061; P < 0.001). CONCLUSION: Our data suggest that identifying baseline pRBD in early-stage PD may help clinicians to choose a better therapeutic strategy so as to prevent or limit neuropsychiatric complications.

Wait and you shall see: sexual delay discounting in hypersexual Parkinson's disease.

Patients with Parkinson's disease may develop impulse control disorders under dopaminergic treatments. Impulse control disorders include a wide spectrum of behaviours, such as hypersexuality, pathological gambling or compulsive shopping. Yet, the neural systems engaged in specific impulse control disorders remain poorly characterized. Here, using model-based functional MRI, we aimed to determine the brain systems involved during delay-discounting of erotic rewards in hypersexual patients with Parkinson's disease (PD+HS), patients with Parkinson's disease without hypersexuality (PD - HS) and controls. Patients with Parkinson's disease were evaluated ON and OFF levodopa (counterbalanced). Participants had to decide between two options: (i) wait for 1.5 s to briefly view an erotic image; or (ii) wait longer to see the erotic image for a longer period of time. At the time of decision-making, we investigated which brain regions were engaged with the subjective valuation of the delayed erotic reward. At the time of the rewarded outcome, we searched for the brain regions responding more robustly after waiting longer to view the erotic image. PD+HS patients showed reduced discounting of erotic delayed rewards, compared to both patients with Parkinson's disease and controls, suggesting that they accepted waiting longer to view erotic images for a longer period of time. Thus, when using erotic stimuli that motivate PD+HS, these patients were less impulsive for the immediate reward. At the brain system level, this effect was paralleled by the fact that PD+HS, as compared to controls and PD - HS, showed a negative correlation between subjective value of the delayed reward and activity of medial prefrontal cortex and ventral striatum. Consistent with the incentive salience hypothesis combining learned cue-reward associations with current relevant physiological state, dopaminergic treatment in PD+HS boosted excessive 'wanting' of rewards and heightened activity in the anterior medial prefrontal cortex and the posterior cingulate cortex, as reflected by higher correlation with subjective value of the option associated to the delayed reward when ON medication as compared to the OFF medication state. At the time of outcome, the anterior medial prefrontal/rostral anterior cingulate cortex showed an interaction between group (PD+HS versus PD - HS) and medication (ON versus OFF), suggesting that dopaminergic treatment boosted activity of this brain region in PD+HS when viewing erotic images after waiting for longer periods of time. Our findings point to reduced delay discounting of erotic rewards in PD+HS, both at the behavioural and brain system levels, and abnormal reinforcing effect of levodopa when PD+HS patients are confronted with erotic stimuli.10.1093/brain/awy298_video1awy298media15983845074001.

Nigrostriatal dopamine transporter availability, and its metabolic and clinical correlates in Parkinson's disease patients with impulse control disorders.

PURPOSE: Previous studies in patients with Parkinson's disease (PD) and impulse control disorders (ICDs) have produced heterogeneous results regarding striatal dopamine transporter (DaT) binding and activity in the mesocorticolimbic network. Our aim here was to study the relationship between striatal DaT availability and cortical metabolism, as well as motor, behavioural and cognitive features of PD patients with ICD. METHODS: In a group of PD patients with ICD (PD-ICD, n = 16) and 16 matched PD patients without ICD (PD-noICD, n = 16), DaT single-photon emission computed tomography (SPECT) imaging (DaTSCAN) was used to study DaT availability in predefined striatal volumes of interest (VOIs): putamen, caudate nucleus and ventral striatum (VS). In addition, the specific association of striatal DaT binding with cortical limbic and associative metabolic activity was evaluated by 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in PD-ICD patients and investigated using statistical parametric mapping (SPM8). Finally, associations between DaT availability and motor, behavioural and cognitive features were assessed. RESULTS: PD-ICD patients had a significantly lower DaT density in the VS than PD-noICD patients, which was inversely associated with ICD severity. Lower DaT availability in the VS was associated with lower FDG uptake in several cortical areas belonging to the limbic and associative circuits, and in other regions involved in reward and inhibition processes (p < 0.0001 uncorrected; k > 50 voxels). No significant results were observed using a higher conservative threshold (p < 0.05; FDR corrected). PD-ICD patients also displayed impairment in interference and attentional Stroop Task execution, and more anxiety, all associated with reduced DaT availability in the VS and caudate nucleus. CONCLUSIONS: ICDs in PD patients are related to reduced DaT binding in the VS, which accounts for dysfunction in a complex cortico-subcortical network that involves areas of the mesolimbic and mesocortical systems, being associated with reward evaluation, salience attribution and inhibitory control processes.

Scales to assess impulsive and compulsive behaviors in Parkinson's disease: Critique and recommendations.

Impulse control disorders (ICDs) and related impulsive and compulsive behaviors (together called ICBs) have been increasingly recognized in the context of Parkinson's disease (PD) and treatment. The International Parkinson's and Movement Disorder Society commissioned a task force to assess available clinical screening instruments and rating scales, including their clinimetric properties, make recommendations regarding their utility, and suggest future directions in scale development and validation. The literature was systematically searched for scales measuring a range of reported ICBs in PD. A scale was designated "recommended" if the scale had been employed in PD studies, been used beyond the group that developed it, and had adequate clinimetric data published for PD. Numerous diagnostic screening tools and severity rating scales were identified for a range of ICBs, including compulsive medication use, punding/hobbyism, walkabout, pathological gambling, hypersexuality, compulsive or binge eating, compulsive buying, reckless driving, compulsive exercise, pyromania, trichotillomania, hoarding, kleptomania, intermittent explosive disorder, and internet addiction. For screening across the range of ICBs (except compulsive medication use), the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's disease (QUIP) and QUIP-Rating Scale (QUIP-RS) are recommended, and for severity rating across the range of ICBs the QUIP-RS and the Ardouin Scale of Behavior in Parkinson's Disease are recommended. The Scale for Outcomes in Parkinson's Disease-Psychiatric Complications is recommended for rating of hypersexuality and the compulsive behaviors gambling/shopping. Further testing of established scales against gold standard diagnostic criteria is urgently required for all other individual ICBs in PD. © 2019 International Parkinson and Movement Disorder Society © 2019 International Parkinson and Movement Disorder Society.

Neuropsychiatric Traits Associated with Refractory Impulse Control Disorder in Parkinson's Disease.

INTRODUCTION: Impulse control disorder (ICD) in Parkinson's disease (PD) is a critical nonmotor symptom with personality or neuropsychiatric traits contributing to ICD. OBJECTIVE: This study aimed to identify predictive traits for persistent or paradoxical aggravation of ICD after dopamine agonist substitution therapy for ICD in PD. METHODS: We conducted a case-control study using a database of a multicenter intervention trial for ICD in PD. The poor-outcome group was defined by showing paradoxical increases in ICD behaviors after the substitution of dopamine agonists with levodopa. We analyzed the pre-intervention personality traits associated with the poor outcome and also evaluated the risk traits for refractory ICD using a receiver-operating characteristic (ROC) curve analysis. RESULTS: The poor-outcome group showed higher levels of anger expression (p =0.007) and obsessive-compulsive traits (p =0.009) compared with the good-outcome group at the pre-intervention state. In the ROC curve analysis, the Obsessive-Compulsive Inventory showed the highest area under the curve with 80.0% sensitivity and 74.3% specificity in discriminating against the poor-outcome group. CONCLUSIONS: Our results suggest that assessment of obsessive compulsiveness may be useful for predicting the refractoriness of ICD behaviors in planning an interventional treatment for ICD in PD.

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

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

Mild Traumatic Brain Injury and Aggression, Impulsivity, and History of Other- and Self-Directed Aggression.

Mild traumatic brain injury (mTBI) is highly prevalent, with an estimated occurrence in the United States of more than 1.3 million per year. While one consequence of mTBI is impulsive aggressive behavior, very few studies have examined the relationship between history of mTBI and aggressive behavior in impulsively aggressive individuals. The authors examined the relationship between history of mTBI in a healthy control group (HC; N=453), a control group with psychiatric disorders (PC; N=486), and individuals with intermittent explosive disorder (IED; N=695), a disorder of primary impulsive aggression. Results demonstrated that IED study participants were significantly more likely to have a history of mTBI (with or without history of a brief loss of consciousness [LOC]) compared with both HC and PC participants. A similar observation was made with regard to self-directed aggression (i.e., suicidal or self-injurious behavior), although group differences were only among those with mTBI with LOC. For both other- and self-directed aggression variables, the authors observed a stepwise increase in dimensional aggression and impulsivity scores across participants as a function of mTBI history. Given that impulsive aggressive behavior begins very early in life, these data are consistent with the hypothesis that lifelong presence of an impulsive aggressive temperament places impulsive aggressive individuals in circumstances that put them at greater risk for mTBI compared with other individuals with and without nonimpulsive aggressive psychopathology.

Impulse control disorders in Parkinson's disease: Review of pathophysiology, epidemiology, clinical features, management, and future challenges.

Impulsive-compulsive behavior (ICB) in Parkinson's disease (PD) suggests a combination of impulse control disorders (ICDs), such as pathological gambling, hypersexuality, compulsive eating, excessive buying, and compulsive behaviors, such as punding, dopamine dysregulation syndrome (DDS), hoarding, and hobbyism. Hypersexuality and gambling are common in male patients while compulsive buying is common in women patients. Recent studies reveal the prevalence of ICB to be more than 25% among the PD patients. The nigrostriatal, mesocortical, and mesolimbic dopaminergic pathways play a crucial role in the pathogenesis of ICDs in PD patients. The greater tonic release of dopamine creates a state of relative dopamine deficit and reduced reward sensation and impulsive behaviors. The major risk factors for ICB are the use of dopamine agonist (DA), male gender, young patient, depression, smoking, drug abuse, Parkin mutation, and family history of ICDs. Single nucleotide polymorphism in dopamine receptors D1, D2, and D3 also acts as a major risk factor. Questionnaire for impulsive-compulsive disorders in PD is the most widely adopted screening tool for the detection of ICB in PD. The major treatment for PD is to discontinue DAs and use prolonged release formulation of the DAs. The role of deep brain stimulation (DBS) and apomorphine in the treatment of ICB is still uncertain. Though DBS can reduce the risk of DDS, it can precipitate new ICBs such as hypersexuality.

Impaired learning of punishments in Parkinson's disease with and without impulse control disorder.

To document specific learning mechanisms in patients with Parkinson's disease (PD) with and without impulse control disorder (ICD). Thirty-two PD patients receiving dopamine replacement therapy (DRT) were investigated. Sixteen were diagnosed with ICD (ICD + ) and 16 PD patients matched for levodopa equivalence dosage, and DRT duration and severity of disease did not show impulsive behavior (non-ICD). Short-term learning of inhibitory control was assessed by an experimental procedure which was intended to mimic everyday life. Correct inhibition especially, had to be learned without reward (passive avoidance), and the failure to inhibit a response was punished (punishment learning). Results were compared to 16 healthy controls (HC) matched for age and sex. In ICD+ patients within-session learning of non-rewarded inhibition was at chance levels. Whereas healthy controls rapidly developed behavioral inhibition, non-ICD patients were also significantly impaired compared to HC, but gradually developed some degree of control. Both patient groups showed significantly decreased learning if the failure to withhold a response was punished. PD patients receiving DRT show impaired ability to acquire both punishment learning and passive avoidance learning, irrespective of whether or not ICD was developed. In ICD + PD patients, behavioral inhibition is nearly absent. Results demonstrate that by means of subtle learning paradigms it is possible to identify PD-DRT patients who show subtle alterations of punishment learning. This may be a behavioral measure for the identification of PD patients who are prone to develop ICD if DRT is continued.

Impulse control disorder, lysosomal malfunction and ATP13A2 insufficiency in Parkinsonism.

Lysosomal transport of cargos in neurons is essential for neuronal proteostasis, transmission and functional motors and behaviours. Lysosomal malfunction including storage disorders is involved in the pathogenesis of Parkinson's disease (PD). Given the unclear molecular mechanisms of diverse defects in PD phenotypes, especially behavioural deficits, this mini review explores the cellular contexts of PD impulse control disorders and the molecular aspects of lysosomal cross-membrane transports. Focuses are paid to trace metal involvements in α-synuclein assembly in Lewy bodies, the functions and molecular interactions of ATP13A2 as ATPase transporters in lysosomal membranes for cross-membrane trafficking and lysosomal homeostasis, and our current understandings of the neural circuits in ICD. Erroneously polarized distributions of cargos such as metals and lipids on each side of lysosomal membranes triggered by gene mutations and deregulated expression of ATP13A2 may thus instigate sensing protein structural changes such as aggregations, organelle degeneration, and specific neuronal ageing and death in Parkinsonism.

Profiles of Emotion Deficits and Adolescent Nonsuicidal Self-Injury in an Inpatient Sample.

This study examined profiles of specific emotion deficits, including poor emotion awareness, reluctance to express emotion, sadness inhibition and dysregulation, and anger inhibition and dysregulation. Self-report questionnaires assessed adolescents' emotion skills and nonsuicidal self-injury (NSSI) engagement, frequency, severity, methods, and age of onset. Latent profile analysis yielded a three-profile solution: Low Deficit (LD; n = 49), Unaware/Anger Dysregulated (UAD; n = 24), and Anger Inhibited (AI; n = 20) profiles. Adolescents in the UAD profile were more likely to engage in NSSI, displayed a higher NSSI frequency, and reported a higher number of NSSI methods when compared to adolescents in the LD profile. No links emerged for NSSI severity or age of onset.

Neurocognitive Findings in Onychophagia (Pathological Nail Biting).

A notable number of people struggle to control the desire to bite their nails, resulting in impairment and distress. Understanding this behavior and the inability to control it has received little research attention. One possible mechanism to understand nail biting is through the use of neurocognitive assessments. Neurocognitive assessments of pathological nail biting, however, are lacking. This analysis assesses the clinical presentation and neurocognitive profile of adults with nail biting relative to participants without nail biting. A total of 87 participants (aged 18-29 years) were recruited for a study on nail biting in young adults. Participants completed diagnostic, self-report, and neurocognitive measures which assessed two cognitive domains - motor impulsivity and cognitive flexibility. In the sample, 34 participants reported current nail biting. The nail biting group showed no significant differences in impulsivity or cognitive flexibility compared to the healthy controls. The lack of association between nail biting and cognitive deficits suggests that perhaps identifying meaningful subtypes of nail biting that reflect distinct pathology from normal grooming behavior may be important.