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ObjectiveTo describe the incidence of, and clinical and neurobiological risk factors for, new-onset impulse control disorder (ICD) symptoms and related behaviours in early Parkinson disease (PD).MethodsThe Parkinson's Progression Markers Initiative is an international, multicenter, prospective study of de novo patients with PD untreated at baseline and assessed annually, including serial dopamine transporter imaging (DAT-SPECT) and ICD assessment (Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease short form, QUIP). Participants were included if they screened negative on the QUIP at baseline. Kaplan-Meier curves and generalised estimating equations examined frequency and predictors of incident ICD symptoms.ResultsParticipants were seen at baseline (n=320), year 1 (n=284), year 2 (n=217) and year 3 (n=96). Estimated cumulative incident rates of ICD symptoms and related behaviours were 8% (year 1), 18% (year 2) and 25% (year 3) and increased each year in those on dopamine replacement therapy (DRT) and decreased in those not on DRT. In participants on DRT, risk factors for incident ICD symptoms were younger age (OR=0.97, p=0.05), a greater decrease in right caudate (OR=4.03, p=0.01) and mean striatal (OR=6.90, p=0.04) DAT availability over the first year, and lower right putamen (OR=0.06, p=0.01) and mean total striatal (OR=0.25, p=0.04) DAT availability at any post-baseline visit.ConclusionsThe rate of incident ICD symptoms increases with time and initiation of DRT in early PD. In this preliminary study, a greater decrease or lower DAT binding over time increases risk of incident ICD symptoms, conferring additional risk to those taking DRT.Clinical trial registrationNCT01141023.

Impulse Control Disorders (ICDs) are increasingly recognized as a significant non-motor complication in Parkinson’s disease (PD), impacting patients and their caregivers. ICDs in PD are primarily associated with dopaminergic treatments, particularly dopamine agonists, though not all patients develop these disorders, indicating a role for genetic and other clinical factors. Studies over the past few years suggest that the mesocorticolimbic reward system, a core neural substrate for impulsivity, is a key contributor to ICDs in PD. Recent advances in neuroimaging have begun to unravel the neurobiological diversity of ICD subtypes. Moreover, recent studies provide valuable insights into the clinical and biologic risk factors for ICDs that could be used as indicators for the development of future preventive strategies or targeted interventions. Indeed, current treatment strategies, which often involve reducing or discontinuing dopamine agonists, are limited in efficacy. Emerging therapies, including behavioral interventions and continuous drug delivery methods, show promise, though further research is needed. This paper provides an updated review of ICD prevalence, mechanisms, assessment, and novel management approaches.

ObjectiveIn this multicentre open-label trial, we compared behavioural and neuropsychiatric symptoms in Parkinson’s disease (PD) patients with impulse control disorders (ICD) treated with dopamine agonists before and 12 weeks after substituting dopamine agonists with an equivalent dose of levodopa/carbidopa slow-release formulation.MethodsBaseline characteristics of 50 PD patients with ICD were compared with those of 60 medicated and 40 drug-naive PD control groups. Neuropsychiatric trait changes in the PD-ICD group were investigated 12 weeks after the intervention. ICD behaviours were assessed via modified Minnesota Impulsive Disorders Interview (mMIDI), whereas parkinsonian severity and neuropsychiatric characters were systematically assessed with the Unified PD Rating Scale (UPDRS) and a predefined neuropsychological assessment battery.ResultsAt baseline, ICD patients showed higher scores in the Neuropsychiatric Inventory and anxiety, anger and obsessive-compulsive traits compared with both PD control groups. In contrast, the three PD groups showed indifference in the impulsivity scales. At 12 weeks post intervention, ICD behaviours significantly improved (p<0.001, Δ modified MIDI score=‒5.27 ± 5.75) along with the UPDRS II daily activity scores (p=0.02, Δ=‒2.07 ± 4.53). Behavioural disinhibition tended to improve (p=0.06), although no significant changes were observed in the Neuropsychiatric Inventory and personality trait scores. Dopamine agonist withdrawal syndrome developed in 5.3% of the PD-ICD group.ConclusionsThis study provides class IV evidence suggesting that switching from dopamine agonists to levodopa/carbidopa slow-release formulations alleviated ICD behaviours in PD patients leading to improvement in daily activities whereas neuropsychiatric traits associated with ICD persisted after the 12-week therapy.Trial registration numberNCT01683253.

Objective: Irritability in disruptive mood dysregulation disorder (DMDD) may be associated with a biased tendency to judge ambiguous facial expressions as angry. We conducted three experiments to explore this bias as a treatment target. We tested: 1) whether youth with DMDD express this bias; 2) whether judgment of ambiguous faces can be altered in healthy youth by training; and 3) whether such training in youth with DMDD is associated with reduced irritability and associated changes in brain function. Methods: Participants in all experiments made happy versus angry judgments of faces that varied along a happy to angry continuum. These judgments were used to quantify a “balance point,” the facial expression at which a participant's judgment switches from predominantly happy to predominantly angry. We first compared balance points in youth with DMDD (n = 63) versus healthy youth (n = 26). We then conducted a double-blind, randomized controlled trial of active versus sham balance-point training in 19 healthy youth. Finally, we piloted open, active balance-point training in 14 youth with DMDD, with 10 completing an implicit functional MRI (fMRI) face-emotion processing task. Results: Relative to healthy youth, DMDD youth manifested a shifted balance point, expressed as a tendency to classify ambiguous faces as angry rather than happy. In both healthy and DMDD youth, active training is associated with a shift in balance point toward more happy judgments. In DMDD, evidence suggests that active training may be associated with decreased irritability and changes in activation in the lateral orbitofrontal cortex. Conclusions: These results set the stage for further research on computer-based treatment targeting interpretation bias of angry faces in DMDD. Such treatment may decrease irritability and alter neural responses to subtle expressions of happiness and anger.

BackgroundImpulse control disorders/other compulsive behaviours (‘ICD behaviours’) occur in Parkinson’s disease (PD), but prospective studies are scarce, and prevalence and clinical characteristics of patients are insufficiently defined.ObjectivesTo assess the presence of ICD behaviours over a 2-year period, and evaluate patients’ clinical characteristics.MethodsA prospective, non-interventional, multicentre study (ICARUS (Impulse Control disorders And the association of neuRopsychiatric symptoms, cognition and qUality of life in ParkinSon disease); SP0990) in treated Italian PD outpatients. Study visits: baseline, year 1, year 2. Surrogate primary variable: presence of ICD behaviours and five ICD subtypes assessed by modified Minnesota Impulsive Disorder Interview (mMIDI).Results1069/1095 (97.6%) patients comprised the Full Analysis Set. Point prevalence of ICD behaviours (mMIDI; primary analysis) was stable across visits: 28.6% (306/1069) at baseline, 29.3% (292/995) at year 1, 26.5% (245/925) at year 2. The most prevalent subtype was compulsive eating, followed by punding, compulsive sexual behaviour, gambling and buying disorder. Patients who were ICD positive at baseline were more likely to be male, younger, younger at PD onset, have longer disease duration, more severe non-motor symptoms (including mood and sexual function), depressive symptoms, sleep impairment and poorer PD-related quality of life. However, they did not differ from the ICD-negative patients in their severity of PD functional disability, motor performance and cognitive function.ConclusionsPrevalence of ICD behaviours was relatively stable across the 2-year observational period. ICD-positive patients had more severe depression, poorer sleep quality and reduced quality of life.

Little is known about the prevalence or correlates of DSM-IV pathological gambling (PG). Data from the US National Comorbidity Survey Replication (NCS-R), a nationally representative US household survey, were used to assess lifetime gambling symptoms and PG along with other DSM-IV disorders. Age of onset (AOO) of each lifetime disorder was assessed retrospectively. AOO reports were used to study associations between temporally primary disorders and the subsequent risk of secondary disorders. Most respondents (78.4%) reported lifetime gambling. Lifetime problem gambling (at least one Criterion A symptom of PG) (2.3%) and PG (0.6%) were much less common. PG was significantly associated with being young, male, and Non-Hispanic Black. People with PG reported first gambling significantly earlier than non-problem gamblers (mean age 16.7 v. 23.9 years, z=12.7, p<0.001), with gambling problems typically beginning during the mid-20s and persisting for an average of 9.4 years. During this time the largest annual gambling losses averaged US$4800. Onset and persistence of PG were predicted by a variety of prior DSM-IV anxiety, mood, impulse-control and substance use disorders. PG also predicted the subsequent onset of generalized anxiety disorder, post-traumatic stress disorder (PTSD) and substance dependence. Although none of the NCS-R respondents with PG ever received treatment for gambling problems, 49.0% were treated at some time for other mental disorders. DSM-IV PG is a comparatively rare, seriously impairing, and undertreated disorder whose symptoms typically start during early adulthood and is frequently secondary to other mental or substance disorders that are associated with both PG onset and persistence.

Background and objective Impulse control disorders (ICD), psychosis and delirium are part of the spectrum of behavioural changes associated with Parkinson’s disease (PD). The diagnostic and therapeutic management of these rather complex neuropsychiatric conditions has been updated in the clinical guideline by the German Society of Neurology (DGN). Methods Recommendations are based on a systematic literature reviews, other relevant guidelines and expert opinion. Results Patients receiving dopamine agonists (DA) therapy should be informed about the symptoms and risks of an ICD and should be routinely screened for ICD symptoms. In the presence of an ICD, DA should be reduced or discontinued and psychotherapeutic treatment may be considered. Non-oral therapies (levodopa/carbidopa intestinal gel infusion or deep brain stimulation) may also be an option for appropriate candidates. Psychosis in PD often has a gradual onset. Cognitive and affective disorders, psychiatric and medical comorbidities as well as polypharmacy are risk factors for a psychosis. Non-pharmacological treatments should be implemented as soon as possible and anti-parkinsonian medications should be adjusted/reduced if feasible. For psychosis associated with PD, quetiapine or clozapine should be used on an as-needed basis and for as short a time as is necessary, with safety monitoring. Delirium in PD may be underdiagnosed due to an overlap with chronic neuropsychiatric features of PD. Although transient by definition, delirium in PD can lead to permanent cognitive decline, motor impairment and increased mortality. Management of delirium includes pharmacological and non-pharmacological interventions. Conclusion The updated guideline encompasses the evidence-based diagnostic, non-pharmacological and pharmacological management of ICD, psychosis and delirium in PD.

This review summarizes neurobiological and genetic findings in behavioural addictions, draws parallels with findings pertaining to substance use disorders, and offers suggestions for future research. Articles concerning brain function, neurotransmitter activity, and family history and (or) genetic findings for behavioural addictions involving gambling, Internet use, video game playing, shopping, kleptomania, and sexual activity were reviewed. Behavioural addictions involve dysfunction in several brain regions, particularly the frontal cortex and striatum. Findings from imaging studies incorporating cognitive tasks have arguably been more consistent than cue-induction studies. Early results suggest white and grey matter differences. Neurochemical findings suggest roles for dopaminergic and serotonergic systems, but results from clinical trials seem more equivocal. While limited, family history and genetic data support heritability for pathological gambling and that people with behavioural addictions are more likely to have a close family member with some form of psychopathology. Parallels exist between neurobiological and genetic and family history findings in substance and nonsubstance addictions, suggesting that compulsive engagement in these behaviours may constitute addictions. To date, findings are limited, particularly for shopping, kleptomania, and sexual behaviour. Genetic understandings are at an early stage. Future research directions are offered.

Affective disorders (depression and anxiety), psychosis, impulse control disorders, and apathy are common and sometimes disabling psychiatric conditions in Parkinson disease (PD). Psychiatric aspects of PD are associated with numerous adverse outcomes, yet in spite of this and their high frequency, there remains incomplete understanding of epidemiology, presentation, risk factors, neural substrate, and management strategies. Psychiatric features are typically co- or multimorbid, and there is great intra- and interindividual variability in presentation [ 1 ]. The neuropathophysiological changes that occur in PD, as well as the association between PD treatment and particular psychiatric disorders, suggest a neurobiological contribution to many psychiatric symptoms. There is evidence that psychiatric disorders in PD are still under-recognized and undertreated, and although psychotropic medication use is common, randomized controlled trials demonstrating efficacy and tolerability are largely lacking. Future research on neuropsychiatric complications in PD should be oriented toward determining modifiable correlates or risk factors, and most importantly, establishing efficacious and well-tolerated treatment strategies.

PurposePrevious 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.MethodsIn 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.ResultsPD-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.ConclusionsICDs 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.