There is an increasing awareness that impulse control disorders (ICDs), including compulsive gambling, buying, sexual behavior, and eating, can occur as a complication of Parkinson’s disease (PD). In addition, other impulsive or compulsive disorders have been reported to occur, including dopamine dysregulation syndrome (DDS) and punding. Case reporting and prospective studies have reported an association between ICDs and the use of dopamine agonists (DAs), particularly at greater dosages, whereas dopamine dysregulation syndrome has been associated with greater dosages of levodopa or short-acting DAs. Data suggest that risk factors for an ICD may include male sex, younger age or younger age at PD onset, a pre-PD history of ICD symptoms, personal or family history of substance abuse or bipolar disorder, and a personality style characterized by impulsiveness. Although psychiatric medications are used clinically in the treatment of ICDs, there is no empiric evidence supporting their use in PD. Therefore, management for clinically significant ICD symptoms should consist of modifications to dopamine replacement therapy, particularly DAs, and there is emerging evidence that such management is associated with an overall improvement in ICD symptomatology. It is important that PD patients be aware that DA use may lead to the development of an ICD, and that clinicians monitor patients as part of routine clinical care. As empirically validated treatments for ICDs are emerging, it will be important to examine their efficacy and tolerability in individuals with cooccurring PD and ICDs.
Nonmotor symptoms of Parkinson's disease (PD) may emerge secondary to the underlying pathogenesis of the disease, while others are recognized side effects of treatment. Inevitably, there is an overlap as the disease advances and patients require higher dosages and more complex medical regimens. The non-motor symptoms that emerge secondary to dopaminergic therapy encompass several domains, including neuropsychiatric, autonomic, and sleep. These are detailed in the paper. Neuropsychiatric complications include hallucinations and psychosis. In addition, compulsive behaviors, such as pathological gambling, hypersexuality, shopping, binge eating, and punding, have been shown to have a clear association with dopaminergic medications. Dopamine dysregulation syndrome (DDS) is a compulsive behavior that is typically viewed through the lens of addiction, with patients needing escalating dosages of dopamine replacement therapy. Treatment side effects on the autonomic system include nausea, orthostatic hypotension, and constipation. Sleep disturbances include fragmented sleep, nighttime sleep problems, daytime sleepiness, and sleep attacks. Recognizing the non-motor symptoms that can arise specifically from dopamine therapy is useful to help optimize treatment regimens for this complex disease.
Hedonistic homeostatic dysregulation is a
neuropsychological behavioural disorder associated with substance
misuse and addiction. The disorder has been recognised as a consequence
of dopamine replacement therapy (DRT) in 15 patients with Parkinson's
disease. The syndrome typically develops in male patients with early
onset Parkinson's disease, and can occur with orally and
subcutaneously administered DRT. These patients take increasing
quantities of their DRT, despite increasingly severe drug induced
dyskinesias, and may develop a cyclical mood disorder with hypomania or
manic psychosis. There is impairment of social and occupational
functioning. Tolerance develops to mood elevating effects of DRT and a
negative affective withdrawal state occurs if the drugs are withdrawn
or doses decreased. The clinical features and guidelines for managing this syndrome are discussed. A set of diagnostic criteria for further
investigating this condition is proposed.
As no comprehensive assessment instrument for impulse control disorders (ICDs) in Parkinson’s disease (PD) exists, the aim of this study was to design and assess the psychometric properties of a self-administered screening questionnaire for ICDs and other compulsive behaviors in PD.
The Questionnaire for Impulsive-Compulsive Disorders in Parkinson’s Disease (QUIP) has 3 sections: Section 1 assesses four ICDs (involving gambling, sexual, buying, and eating behaviors), Section 2 other compulsive behaviors (punding, hobbyism and walkabout), and Section 3 compulsive medication use. For validation, a convenience sample of 157 PD patients at 4 movement disorders centers first completed the QUIP, and then was administered a diagnostic interview by a trained rater blinded to the QUIP results. A shortened instrument (QUIP-S) was then explored.
The discriminant validity of the QUIP was high for each disorder or behavior (receiver operating characteristic area under the curve [ROC AUC]: gambling=0.95, sexual behavior=0.97, buying=0.87, eating=0.88, punding=0.78, hobbyism=0.93, walkabout=0.79). On post hoc analysis, the QUIP-S ICD section had similar properties (ROC AUC: gambling=0.95, sexual behavior=0.96, buying=0.87, eating=0.88). When disorders/behaviors were combined, the sensitivity of the QUIP and QUIP-S to detect an individual with any disorder was 96% and 94%, respectively.
Scores on the QUIP appear to be valid as a self-assessment screening instrument for a range of ICDs and other compulsive behaviors that occur in PD, and a shortened version may perform as well as the full version. A positive screen should be followed by a comprehensive, clinical interview to determine the range and severity of symptoms, as well as need for clinical management.
Parkinson’s disease; impulse control disorders; dopamine dysregulation syndrome; punding; pathological gambling
This study investigates the prevalence and demographic characteristics of hypersexuality in Parkinson’s disease (PD). Impulse control disorders in PD patients have been associated with dopamine agonist therapy. Moreover, hypersexuality and pathological gambling have been associated with males, while females may be inherently thought to be more likely to participate in compulsive shopping and binge-eating behaviors. In this study, a screening mail-in survey was sent to all PD patients at a single Movement Disorders Center. One hundred forty one of 400 (35.3%) research packets were returned completed. Fifteen of 141 patients met initial screening criteria for hypersexual behavior. After detailed interview, only 6/141 (4.3%) of PD patients met criteria for pathologic hypersexual behavior. These behaviors included: compulsive masturbation, prostitution, and paraphilias. Patients with a younger age of PD onset were more likely to exhibit hypersexual behavior. Unlike previous report, no significant association was found between hypersexuality and gender or dopamine agonist use. Rather, this study suggests that physicians should be vigilant for hypersexual behavior in all PD patients, regardless of gender and PD medication regimen. Ultimately, given the innate sensitivity of the topic and survey limitations, it is very likely that hypersexual behavior in our cohort, as it is in the general PD population, has been under-reported.
Parkinson’s disease; hypersexuality; impulsive behavior; dopamine agonists
Impulse control disorders and related disorders (hobbyism-punding and dopamine dysregulation syndrome) occur in 15% to 20% of Parkinson’s disease (PD) patients. We assessed the validity and reliability of the Questionnaire for Impulsive-Compulsive Disorders in Parkinson’s Disease–Rating Scale (QUIP-RS), a rating scale designed to measure severity of symptoms and support a diagnosis of impulse control disorders and related disorders in PD. A convenience sample of PD patients at a movement disorders clinic self-completed the QUIP-RS and were administered a semistructured diagnostic interview by a blinded trained rater to assess discriminant validity for impulse control disorders (n = 104) and related disorders (n = 77). Subsets of patients were assessed to determine interrater reliability (n = 104), retest reliability (n = 63), and responsiveness to change (n = 29). Adequate cutoff points (both sensitivity and specificity values >80% plus acceptable likelihood ratios) were established for each impulse control disorder and hobbyism-punding. Interrater and retest reliability (intraclass correlation coefficient r) were >0.60 for all disorders. Participants in an impulse control disorder treatment study who experienced full (t = 3.65, P = .004) or partial (t = 2.98, P = .01) response demonstrated significant improvement on the rating scale over time, while nonresponders did not (t = 0.12, P = .91). The QUIP-RS appears to be valid and reliable as a rating scale for impulse control disorders and related disorders in PD. Preliminary results suggest that it can be used to support a diagnosis of these disorders, as well as to monitor changes in symptom severity over time.
dopamine agonists; impulse control disorder; Parkinson’s disease
Impulsive–compulsive disorders such as pathological gambling, hypersexuality, compulsive eating, and shopping are side effects of the dopaminergic therapy for Parkinson’s disease. With a lower prevalence, these disorders also appear in the general population. Research in the last few years has discovered that these pathological behaviors share features similar to those of substance use disorders (SUD), which has led to the term “behavioral addictions”. As in SUDs, the behaviors are marked by a compulsive drive toward and impaired control over the behavior. Furthermore, animal and medication studies, research in the Parkinson’s disease population, and neuroimaging findings indicate a common neurobiology of addictive behaviors. Changes associated with addictions are mainly seen in the dopaminergic system of a mesocorticolimbic circuit, the so-called reward system. Here we outline neurobiological findings regarding behavioral addictions with a focus on dopaminergic systems, relate them to SUD theories, and try to build a tentative concept integrating genetics, neuroimaging, and behavioral results.
Behavioral addictions; Pathological gambling; Binge eating; Compulsive buying; Hypersexuality; Substance use disorders; Mesocorticolimbic circuit; Reward system; Dopamine; Parkinson; Parkinson’s disease; Neurobiology; Risk factors; Impulse control disorders; Functional anatomy
Impulse control disorders (ICD) (most commonly pathologic gambling, hypersexuality, and uncontrollable spending) and compulsive behaviors can be triggered by dopaminergic therapies in Parkinson disease (PD). ICD are especially prevalent in patients receiving a dopamine agonist as part of their treatment regimen for PD, and have also been reported when dopamine agonists are used for other indications (e.g., restless legs syndrome). Although these iatrogenic disorders are common, affecting 1 in 7 patients with PD on dopamine agonists, they often elude detection by the treating physician. ICD lead to serious consequences, causing significant financial loss and psychosocial morbidity for many patients and families. ICD can appear at any time during treatment with dopamine agonists, sometimes within the first few months, but most often after years of treatment, particularly when patients receive dopamine agonists and levodopa together. In most cases ICD resolve if the dopamine agonist is withdrawn, and PD motor symptoms are managed with levodopa monotherapy. Familiarity with the clinical aspects, risk factors, pathophysiology, and management of ICD is essential for physicians using dopaminergic therapies to treat PD and other disorders.
Risk-taking behavior is characterized by pursuit of reward in spite of potential negative consequences. Dopamine neurotransmission along the mesocorticolimbic pathway is a potential modulator of risk behavior. In patients with Parkinson's Disease (PD), impulse control disorder (ICD) can result from dopaminergic medication use, particularly Dopamine Agonists (DAA). Behaviors associated with ICD include hypersexuality as well as compulsive gambling, shopping, and eating, and are potentially linked to alterations to risk processing. Using the Balloon Analogue Risk task, we assessed the role of agonist therapy on risk-taking behavior in PD patients with (n=22) and without (n=19) active ICD symptoms. Patients performed the task both ‘on’ and ‘off’ DAA. DAA increased risk-taking in PD patients with active ICD symptoms, but did not affect risk behavior of PD controls. DAA dose was also important in explaining risk behavior. Both groups similarly reduced their risk-taking in high compared to low risk conditions and following the occurrence of a negative consequence, suggesting that ICD patients do not necessarily differ in their ability to process and adjust to some aspects of negative consequences. Our findings suggest dopaminergic augmentation of risk-taking behavior as a potential contributing mechanism for the emergence of ICD in PD patients.
Impulse Control Disorders; Dopamine Agonists; Parkinson Disease; Risk behavior
Of 96 Parkinson’s disease (PD) patients at the University of Florida Movement Disorders Center, one (1%) met diagnostic criteria for binge eating disorder (BED). Eight (8.3%) exhibited subthreshold BED. Psychometric criteria classified problem gambling in 17.8%, hoarding in 8.3%, buying in 11.5%, hypersexuality in 1.0%, and mania in 1.0% of patients. More overeaters met psychometric criteria for at least one additional impulse control disorder (67% vs. 29%). No more overeaters than non-overeaters were taking a dopamine agonist (44% vs. 41%). More overeaters had a history of subthalamic DBS (44% vs. 14%). History of DBS was the only independent predictor of overeating.
Parkinson’s disease; binge eating; impulse control disorders
The dopamine agonists ropinirole and pramipexole exhibit highly specific affinity for the cerebral dopamine D3 receptor. Use of these medications in Parkinson's disease has been complicated by the emergence of pathologic behavioral patterns such as hypersexuality, pathologic gambling, excessive hobbying, and other circumscribed obsessive-compulsive disorders of impulse control in people having no history of such disorders. These behavioral changes typically remit following discontinuation of the medication, further demonstrating a causal relationship. Expression of the D3 receptor is particularly rich within the limbic system, where it plays an important role in modulating the physiologic and emotional experience of novelty, reward, and risk assessment. Converging neuroanatomical, physiological, and behavioral science data suggest the high D3 affinity of these medications as the basis for these behavioral changes. These observations suggest the D3 receptor as a therapeutic target for obsessive-compulsive disorder and substance abuse, and improved understanding of D3 receptor function may aid drug design of future atypical antipsychotics.
Questions exist regarding the validity of patient-reporting of psychiatric symptoms in Parkinson’s disease (PD). We assessed observer variability and validity in reporting of impulse control disorder (ICD) symptoms in PD by using the Questionnaire for Impulsive-Compulsive Disorders in Parkinson’s Disease (QUIP). PD patients and their informants (71 pairs) completed the QUIP to assess four ICDs (compulsive gambling, buying, sexual behavior, and eating) in patients. Trained raters then administered a diagnostic interview. Sensitivity of the QUIP for a diagnosed ICD was 100% for both patient- and informant-completed instruments, and specificity was 75% for both raters. Approximately 40% of patients without an ICD diagnosis had a positive QUIP, suggesting that many PD patients experience subsyndromal ICD symptoms that require ongoing monitoring. Agreement between patient- and informant-reporting of any ICD behaviors on the QUIP was moderate (kappa = 0.408), and for individual ICDs was highest for gambling (kappa = 0.550). Overall, a negative QUIP from either the patient or informant rules out the possibility of an ICD, while a positive QUIP requires a follow-up diagnostic interview and ongoing monitoring to determine if symptoms currently are, or in the future become, clinically significant.
Impulse control disorders; Parkinson’s disease; QUIP
To determine the frequency and correlates of impulse control disorders (ICDs) in Parkinson’s disease (PD).
An unstructured screening interview for ICDs (compulsive gambling, buying, and sexual behavior) followed by a telephone-administered structured interview for screen-positive patients.
Two university-affiliated movement disorders centers.
A convenience sample of 272 patients with idiopathic PD who were screened for psychiatric complications.
Main Outcome Measures
Presence of compulsive gambling, buying, or sexual behavior as assessed by the Minnesota Impulsive Disorders Interview.
Eighteen (6.6%) PD patients met criteria for an ICD at some point during the course of PD, including 11 (4.0%) with an active ICD. Compulsive gambling and compulsive sexual behavior were equally common. In a multivariate model, treatment with a dopamine agonist (P = .01) and a history of ICD symptomatology prior to PD onset (P = .02) predicted current ICD. There were no differences between the dopamine agonists in their association with ICDs (P = .21), and daily doses of dopamine agonists were higher in patients with an ICD than in dopamine agonist-treated patients without an ICD (P < .001).
PD patients treated with a dopamine agonist should be made aware of the risk of developing an ICD and monitored clinically. As dopamine agonists are increasing being used for other indications, future research should assess the dopamine agonist-associated risk for ICDs in other populations.
Impulse control disorders are a psychiatric condition characterized by the failure to resist an impulsive act or behavior that may be harmful to self or others. In movement disorders, impulse control disorders are associated with dopaminergic treatment, notably dopamine agonists (DAs). Impulse control disorders have been studied extensively in Parkinson’s disease, but are also recognized in restless leg syndrome and atypical Parkinsonian syndromes. Epidemiological studies suggest younger age, male sex, greater novelty seeking, impulsivity, depression and premorbid impulse control disorders as the most consistent risk factors. Such patients may warrant special monitoring after starting treatment with a DA. Various individual screening tools are available for people without Parkinson’s disease. The Questionnaire for Impulsive-Compulsive Disorders in Parkinson’s Disease has been developed specifically for Parkinson’s disease. The best treatment for impulse control disorders is prevention. However, after the development of impulse control disorders, the mainstay intervention is to reduce or discontinue the offending anti-Parkinsonian medication. In refractory cases, other pharmacological interventions are available, including neuroleptics, antiepileptics, amantadine, antiandrogens, lithium and opioid antagonists. Unfortunately, their use is only supported by case reports, small case series or open-label clinical studies. Prospective, controlled studies are warranted. Ongoing investigations include naltrexone and nicotine.
Impulse control disorders; Parkinson’s disease; restless leg syndrome; parkinsonism; dopamine agonist; non-motor complication; neurobehavioural
In this review we report novel sensitive imaging biomarkers for Parkinson’s disease (PD) and its atypical variants. Diffusion tensor imaging and transcranial brain sonography are potentially promising techniques that can differentiate typical PD from atypical variants (multiple system atrophy and progressive supranuclear palsy) and from benign tremor disorders. Non-motor symptoms, such as dementia, depression, and sleep disruption, are often more distressing to PD patients than their slowness and stiffness. Dopamine replacement treatment can also lead to complications such as dyskinesias, impulse control disorders, and psychosis. Recent positron emission tomography studies have helped to clarify the physiopathological mechanisms underlying dementia and compulsive gambling in PD and provide a rationale for therapeutic strategies.
Disordered dopamine neurotransmission is implicated in mediating impulsiveness across a range of behaviors and disorders including addiction, compulsive gambling, attention-deficit/hyperactivity disorder, and dopamine dysregulation syndrome. Whereas existing theories of dopamine function highlight mechanisms based on aberrant reward learning or behavioral disinhibition, they do not offer an adequate account of the pathological hypersensitivity to temporal delay that forms a crucial behavioral phenotype seen in these disorders. Here we provide evidence that a role for dopamine in controlling the relationship between the timing of future rewards and their subjective value can bridge this explanatory gap. Using an intertemporal choice task, we demonstrate that pharmacologically enhancing dopamine activity increases impulsivity by enhancing the diminutive influence of increasing delay on reward value (temporal discounting) and its corresponding neural representation in the striatum. This leads to a state of excessive discounting of temporally distant, relative to sooner, rewards. Thus our findings reveal a novel mechanism by which dopamine influences human decision-making that can account for behavioral aberrations associated with a hyperfunctioning dopamine system.
Both binge eating disorder (BED) and pathological gambling (PG) are characterized by impairments in impulse control. Subsyndromal levels of PG have been associated with measures of adverse health. The nature and significance of PG features in individuals with BED is unknown. Ninety-four patients with BED (28 men and 66 women) were classified by gambling group based on inclusionary criteria for Diagnostic and Statistical Manual-IV (DSM-IV) PG and compared on a range of behavioral, psychological and eating disorder (ED) psychopathology variables. One individual (1.1% of the sample) met criteria for PG, although 18.7% of patients with BED displayed one or more DSM-IV criteria for PG, hereafter referred to as problem gambling features. Men were more likely than women to have problem gambling features. BED patients with problem gambling features were distinguished by lower self-esteem and greater substance problem use. After controlling for gender, findings of reduced self-esteem and increased substance problem use among patients with problem gambling features remained significant. In patients with BED, problem gambling features are associated with a number of heightened clinical problems.
Binge eating; Gambling; Substance abuse; Obesity; Gender differences
A 55-year-old male with idiopathic Parkinson's disease developed three behavioral changes under combination therapy with selegiline, cabergoline and levodopa. Co-existent behaviors included severe pathological gambling, punding and novel skills in writing poetry (published poetry books). Brain [18F]fluorodopa PET imaging showed decreased tracer uptake in the striatum contralateral to the predominant motor symptoms, consistent with the clinical diagnosis of Parkinson's disease. Uptake in the ventral striatum was markedly high. Brain MRI before and after behavioral changes showed no pathological findings. The patient was diagnosed as having Parkinson's disease together with DSM-IV criteria-fulfilling pathological gambling and punding-like stereotyped behavior. There are no established criteria for the classification of emerged artistic creativity, although there are descriptions of the phenomenon in the literature. Inspired by the case, we conducted a preliminary survey – including 290 patients with Parkinson's disease – exploring the possible relationship between creativity and impulsive-compulsive behaviors. The case, supported by the results of the survey, adds to the cumulative evidence of the association between dopaminergic medication and enhanced creativity, and suggests a possible linkage between increased artistic creativity and impulsive-compulsive behaviors in Parkinson's disease. Furthermore, it could be speculated that the high mesolimbic dopamine function might relate to the behavioral changes observed in this patient, and is suggestive of the overlapping neurobiological mechanisms of compulsive behaviors and artistic creativity.
Parkinson's disease; Impulse control disorder; Gambling; Punding; Mesolimbic; Dopamine; Ventral striatum; Creativity
To describe, in the context of DSM-V, how a focus on addiction and compulsion is emerging in the consideration of pathological gambling (PG).
A systematic literature review of evidence for the proposed re-classification of PG as an addiction.
Findings include: 1. Phenomenological models of addiction highlighting a motivational shift from impulsivity to compulsivity associated with a protracted withdrawal syndrome and blurring of the ego-syntonic/ego-dystonic dichotomy; 2. Common neurotransmitter (dopamine, serotonin) contributions to PG and substance use disorders (SUDs); 3. Neuroimaging support for shared neurocircuitries between “behavioral” and substance addictions and differences between obsessive-compulsive disorder (OCD), impulse control disorders (ICDs) and SUDs; 4. Genetic findings more closely related to endophenotypic constructs like compulsivity and impulsivity than to psychiatric disorders; 5. Psychological measures such as harm avoidance identifying a closer association between SUDs and PG than with OCD; 6. Community and pharmaco-therapeutic trials data supporting a closer association between SUDs and PG than with OCD. Adapted behavioral therapies, such as exposure therapy appear applicable to OCD, PG, or SUDs, suggesting some commonalities across disorders.
PG shares more similarities with SUDs than with OCD. Similar to the investigation of impulsivity, studies of compulsivity hold promising insights concerning the course, differential diagnosis and treatment of PG, SUDs, and OCD.
Compulsivity; Impulsivity; Addiction; Pathological Gambling; Endophenotypes
OBJECTIVE: To determine the frequency of new-onset compulsive gambling or hypersexuality among regional patients with Parkinson disease (PD), ascertaining the relationship of these behaviors to PD drug use.
PATIENTS AND METHODS: We retrospectively reviewed the medical records of patients from 7 rural southeastern Minnesota counties who had at least 1 neurology appointment for PD between July 1, 2004, and June 30, 2006. The main outcome measure was compulsive gambling or hypersexuality developing after parkinsonism onset, including the temporal relationship to PD drug use.
RESULTS: Of 267 patients with PD who met the study inclusion criteria, new-onset gambling or hypersexuality was documented in 7 (2.6%). All were among the 66 patients (10.6%) taking a dopamine agonist. Moreover, all 7 (18.4%) were among 38 patients taking therapeutic doses (defined as ≥2 mg of pramipexole or 6 mg of ropinirole daily). Behaviors were clearly pathologic and disabling in 5: 7.6% of all patients taking an agonist and 13.2% of those taking therapeutic doses. Of the 5 patients, 2 had extensive treatment for what was considered a primary psychiatric problem before the agonist connection was recognized.
CONCLUSION: Among the study patients with PD, new-onset compulsive gambling or hypersexuality was documented in 7 (18.4%) of 38 patients taking therapeutic doses of dopamine agonists but was not found among untreated patients, those taking subtherapeutic agonist doses, or those taking carbidopa/levodopa alone. Behaviors abated with discontinuation of agonist therapy or dose reduction. Because this is a retrospective study, cases may have been missed, and hence this study may reflect an underestimation of the true frequency. Physicians who care for patients taking these drugs should recognize the drug's potential to induce pathologic syndromes that sometimes masquerade as primary psychiatric disease.
In patients with Parkinson disease, new-onset compulsive gambling or hypersexuality was documented in 7 of 38 patients taking therapeutic doses of dopamine agonists but was not found among untreated patients, those taking subtherapeutic agonist doses, or those taking carbidopa/levodopa alone.
To further refine our understanding of impulsivity, obsessions, and compulsions in anorexia nervosa (AN) by isolating which behaviors—binge eating, purging, or both—are associated with these features.
We conducted regression analyses with binge eating, purging, and the interaction of binge eating with purging as individual predictors of scores for impulsivity, obsessions, and compulsions in two samples of women with AN (n = 1373).
Purging, but not binge eating, was associated with higher scores of impulsivity, obsessions and compulsions. Purging was also associated with worst eating rituals and with worst eating preoccupations.
Our results suggest that purging, compared with binge eating, may be a stronger correlate of impulsivity, obsessions, and compulsions in AN.
anorexia nervosa; impulsivity; compulsivity; binge eating; purging
Links between impulsive compulsive behaviors in treated Parkinson’s disease, behavioral addictions and substance abuse have been postulated, but no direct comparisons have been carried out so far.
We directly compared patients with Parkinson’s disease with and without impulsive compulsive behaviors with illicit drug abusers, pathological gamblers and age-matched healthy controls using the beads task, a test of reflection impulsivity and a working memory task.
We found that all patients with Parkinson’s disease made more impulsive and irrational choices than the control group. Parkinson’s disease patients who had an impulsive compulsive behavior showed similar behavior to illicit substance abusers whereas patients without impulsive compulsive behaviors more closely resembled pathological gamblers. In contrast we found no difference in working memory performance within the Parkinson’s disease groups. However Parkinson’s disease patients without impulsive compulsive behaviors remembered distractors significantly less than all other patients during working memory tests.
We were able to correctly classify 96% of the Parkinson’s disease patients with respect to whether or not they had an impulsive compulsive behavior by analyzing 3 trials of the 80/20 loss condition of the beads task with a negative prediction value of 92.3% and we propose that this task may prove to be a powerful screening tool to detect an impulsive compulsive behavior in Parkinson’s disease. Our results also suggest that intact cortical processing and less distractibility in Parkinson’s disease patients without impulsive compulsive behaviors may protect them from developing behavioral addictions.
Impulsive compulsive behavior; Parkinson’s disease; reflection impulsivity; pathological gambling; substance abuse; beads task
Pathological gambling is an impulse control disorder reported in association with dopamine agonists used to treat Parkinson’s disease. Although impulse control disorders are conceptualized as lying within the spectrum of addictions, little neurobiological evidence exists to support this belief. Functional imaging studies have consistently demonstrated abnormalities of dopaminergic function in patients with drug addictions, but to date no study has specifically evaluated dopaminergic function in Parkinson’s disease patients with impulse control disorders. We describe results of a [11C] raclopride positron emission tomography (PET) study comparing dopaminergic function during gambling in Parkinson’s disease patients, with and without pathological gambling, following dopamine agonists. Patients with pathological gambling demonstrated greater decreases in binding potential in the ventral striatum during gambling (13.9%) than control patients (8.1%), likely reflecting greater dopaminergic release. Ventral striatal bindings at baseline during control task were also lower in patients with pathological gambling. Although prior imaging studies suggest that abnormality in dopaminergic binding and dopamine release may be markers of vulnerability to addiction, this study presents the first evidence of these phenomena in pathological gambling. The emergence of pathological gambling in a number of Parkinson’s disease patients may provide a model into the pathophysiology of this disorder.
PMID: 19346328 CAMSID: cams2369
Parkinson’s disease; dopamine; impulse control disorders; pathological gambling; PET; functional imaging
Failures in cortical control of fronto-striatal neural circuits may underpin impulsive and compulsive acts. In this narrative review, we explore these behaviors from the perspective of neural processes and consider how these behaviors and neural processes contribute to mental disorders such as obsessive–compulsive disorder (OCD), obsessive–compulsive personality disorder, and impulse-control disorders such as trichotillomania and pathological gambling. We present findings from a broad range of data, comprising translational and human endophenotypes research and clinical treatment trials, focussing on the parallel, functionally segregated, cortico-striatal neural projections, from orbitofrontal cortex (OFC) to medial striatum (caudate nucleus), proposed to drive compulsive activity, and from the anterior cingulate/ventromedial prefrontal cortex to the ventral striatum (nucleus accumbens shell), proposed to drive impulsive activity, and the interaction between them. We suggest that impulsivity and compulsivity each seem to be multidimensional. Impulsive or compulsive behaviors are mediated by overlapping as well as distinct neural substrates. Trichotillomania may stand apart as a disorder of motor-impulse control, whereas pathological gambling involves abnormal ventral reward circuitry that identifies it more closely with substance addiction. OCD shows motor impulsivity and compulsivity, probably mediated through disruption of OFC-caudate circuitry, as well as other frontal, cingulate, and parietal connections. Serotonin and dopamine interact across these circuits to modulate aspects of both impulsive and compulsive responding and as yet unidentified brain-based systems may also have important functions. Targeted application of neurocognitive tasks, receptor-specific neurochemical probes, and brain systems neuroimaging techniques have potential for future research in this field.
impulsive; compulsive; endophenotypes; serotonin; dopamine; Cognition; Psychiatry & Behavioral Sciences; Animal models; Biological Psychiatry; OCD; impulsivity; compulsivity; translational
Many common psychiatric conditions, such as attention deficit/hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), Parkinson's disease, addiction and pathological gambling are linked by a failure in the mechanisms that control, or inhibit, inappropriate behavior. Models of rat behavioral inhibition permit us to study in detail the anatomical and pharmacological bases of inhibitory failure, using methods that translate directly with patient assessment in the clinic. This review updates current ideas relating to behavioral inhibition based on two significant lines of evidence from rat studies:
(1) To integrate new findings from the stop-signal task into existing models of behavioral inhibition, in particular relating to ‘impulsive action’ control. The stop-signal task has been used for a number of years to evaluate psychiatric conditions and has recently been translated for use in the rat, bringing a wealth of new information to behavioral inhibition research.
(2) To consider the importance of the subthalamic nucleus (STN) in the neural circuitry of behavioral inhibition. This function of this nucleus is central to a number of ‘disinhibitory’ disorders such as Parkinson's disease and OCD, and their therapies, but its role in behavioral inhibition is still undervalued, and often not considered in preclinical models of behavioral control.
Integration of these findings has pinpointed the orbitofrontal cortex (OF), dorsomedial striatum (DMStr) and STN within a network that normally inhibits many forms of behavior, including both impulsive and compulsive forms. However, there are distinct differences between behavioral subtypes in their neurochemical modulation.
This review brings new light to the classical view of the mechanisms that inhibit behavior, in particular suggesting a far more prominent role for the STN, a structure that is usually omitted from conventional behavioral-inhibition networks. The OF–DMStr–STN circuitry may form the basis of a control network that defines behavioral inhibition and that acts to suppress or countermand many forms of inappropriate or maladaptive behavior.
Dopamine; Serotonin; Noradrenaline; Atomoxetine; Orbitofrontal; Subthalamic nucleus; Dorsomedial striatum; Nucleus accumbens; SSRT; Premature response; Perseverative response