Development Of Impulse Control Disorders Research Articles

Variability in neuronal expression of dopamine receptors and transporters in the substantia nigra

Parkinson's disease (PD) patients have increased susceptibility to impulse control disorders. Recent studies have suggested that alterations in dopamine receptors in the midbrain underlie impulsive behaviors and that more impulsive individuals, including patients with PD, exhibit increased occupancy of their midbrain dopamine receptors. The cellular location of dopamine receptor subtypes and transporters within the human midbrain may therefore have important implications for the development of impulse control disorders in PD. The localization of the dopamine receptors (D1-D5) and dopamine transporter proteins in the upper brain stems of elderly adult humans (n = 8) was assessed using single immunoperoxidase and double immunofluorescence (with tyrosine hydroxylase to identify dopamine neurons). The relative amount of protein expressed in dopamine neurons from different regions was assessed by comparing their relative immunofluorescent intensities. The midbrain dopamine regions associated with impulsivity (medial nigra and ventral tegmental area [VTA]) expressed less dopamine transporter on their neurons than other midbrain dopamine regions. Medial nigral dopamine neurons expressed significantly greater amounts of D1 and D2 receptors and vesicular monoamine transporter than VTA dopamine neurons. The heterogeneous pattern of dopamine receptors and transporters in the human midbrain suggests that the effects of dopamine and dopamine agonists are likely to be nonuniform. The expression of excitatory D1 receptors on nigral dopamine neurons in midbrain regions associated with impulsivity, and their variable loss as seen in PD, may be of particular interest for impulse control.

Effects of pramipexole on the processing of rewarding and aversive taste stimuli

Pramipexole, a D2/D3 dopamine receptor agonist, has been implicated in the development of impulse control disorders in patients with Parkinson's disease. Investigation of single doses of pramipexole in healthy participants in reward-based learning tasks has shown inhibition of the neural processing of reward, presumptively through stimulation of dopamine autoreceptors. This study aims to examine the effects of pramipexole on the neural response to the passive receipt of rewarding and aversive sight and taste stimuli. We used functional magnetic resonance imaging to examine the neural responses to the sight and taste of pleasant (chocolate) and aversive (mouldy strawberry) stimuli in 16 healthy volunteers who received a single dose of pramipexole (0.25 mg) and placebo in a double-blind, within-subject, design. Relative to placebo, pramipexole treatment reduced blood oxygen level-dependent activation to the chocolate stimuli in the areas known to play a key role in reward, including the ventromedial prefrontal cortex, the orbitofrontal cortex, striatum, thalamus and dorsal anterior cingulate cortex. Pramipexole also reduced activation to the aversive condition in the dorsal anterior cingulate cortex. There were no effects of pramipexole on the subjective ratings of the stimuli. Our results are consistent with an ability of acute, low-dose pramipexole to diminish dopamine-mediated responses to both rewarding and aversive taste stimuli, perhaps through an inhibitory action of D2/3 autoreceptors on phasic burst activity of midbrain dopamine neurones. The ability of pramipexole to inhibit aversive processing might potentiate its adverse behavioural effects and could also play a role in its proposed efficacy in treatment-resistant depression.

Diagnosis and treatment of impulse control disorders in patients with movement disorders.

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.

Clinical features of dopamine agonist withdrawal syndrome in a movement disorders clinic

BackgroundRecently, symptoms similar to addictive drug withdrawal have been reported in a structured longitudinal study of patients with idiopathic Parkinson's Disease (PD) withdrawing from dopamine agonists (DA): the dopamine agonist...

Impulse Control Disorders in Parkinson’s Disease: A Review

The development of Impulse Control Disorders (ICDs) in Parkinson’s disease (PD) is a recognised iatrogenic complication associated with the use of dopamine agonists. The prevalence of ICDs has been reported to be as high as 14% in studies conducted in Europe and North America. Early case reports and recent large-scale studies have shown that clinical features associated with the development of PD-related ICDs include novelty-seeking personality traits, early onset PD and a past history of psychiatric conditions. More recent studies have also suggested that ICDs may be associated with deep brain stimulation and dyskinesias. Moreover, there is heterogeneity in the clinical features associated with the range of ICDs, with studies pointing out that compulsive sexual behaviours and binge eating have fewer clinical features in common than compulsive buying and pathological gambling. The recent increase in the number of functional neuroimaging studies on patients with PD and ICDs, particularly those with pathological gambling, has provided a unique opportunity to understand the neurobiology of the disorder, and has indicated an abnormality in the meso-limbic dopaminergic pathways. Further studies directly comparing ICD sufferers with and without PD will provide valuable knowledge to aid in the management of both patient groups. This review will provide a clinical overview of impulse control behaviours in PD, including both commonly reported ICDs and other related impulsive-compulsive behaviours observed in PD. Keywords: Dopamine dysregulation syndrome, Binge eating, Compulsive buying, Compulsive sexual behaviour, Functional imaging, Impulse control disorder, Parkinson disease, Pathological gambling, Phenomenology, Compulsive Sexual Behaviour

Alexithymia Is Associated With Impulsivity in Newly-Diagnosed, Drug-Naïve Patients With Parkinson’s Disease: An Affective Risk Factor for the Development of Impulse-Control Disorders?

Alexithymia Is Associated With Impulsivity in Newly-Diagnosed, Drug-Naïve Patients With Parkinson’s Disease: An Affective Risk Factor for the Development of Impulse-Control Disorders?

Role of genetic polymorphisms of the dopaminergic system in Parkinson’s disease patients with impulse control disorders

BackgroundThe mechanisms underlying the development of impulse control disorders (ICDs) like compulsive gambling, buying, sexual, and eating behaviors in Parkinson’s disease (PD) are debated. We assessed whether allelic variants of dopamine D2 receptors (DRD2), catechol-O-methyltransferase (COMT) and dopamine transporter (DAT) were associated with the development of ICDs in PD. MethodWe enrolled 89 idiopathic PD patients (48 without ICDs and 41 with ICDs). All patients were screened with the Minnesota Impulsive Disorders Interview (MIDI) and fulfilled DSM-IV criteria for the ICD positive cohort. Differences in the frequency of the genotypes between ICDs and non-ICDs groups were assessed using the χ2 test. ResultsGenotyping was performed for variants of the DRD2 Taq1A (rs1800497), COMT Val158Met (rs4680), DAT1 (3′ UTR 40bp VNTR). Variants of DRD2 Taq1A, COMT and DAT1 were not associated with the risk of developing ICDs. ConclusionIn our study, there were no differences in the frequency of variant of DRD2 Taq1A, COMT and DAT1 between the two groups. Polymorphisms of dopaminergic genes do not play a relevant role in the development of ICD in PD suggesting that ICD originate from inability to filter inappropriate behaviors triggered by dopaminergic therapy.

Impulsive choice—Parkinson disease and dopaminergic therapy

Treatment of Parkinson disease (PD) with dopaminergic medication is associated with the development of impulse control disorders (ICDs). A new study suggests that, irrespective of medication, patients with PD are more likely to make impulsive decisions. How and why might the risk of ICDs be increased in patients with this disease?

Impulse Control Disorders Following Deep Brain Stimulation of the Subthalamic Nucleus in Parkinson's Disease: Clinical Aspects

Parkinson's disease (PD) has been associated with the development of impulse control disorders (ICDs), possibly due to overstimulation of the mesolimbic system by dopaminergic medication. Preliminary reports have suggested that deep brain stimulation (DBS), a neurosurgical procedure offered to patients with treatment-resistant PD, affects ICD in a twofold way. Firstly, DBS allows a decrease in dopaminergic medication and hence causes an improvement in ICDs. Secondly, some studies have proposed that specific ICDs may develop after DBS. This paper addresses the effects of DBS on ICDs in patients with PD. A literature search identified four original studies examining a total of 182 patients for ICDs and nine case reports of 39 patients that underwent DBS and developed ICDs at some point. Data analysis from the original studies did not identify a significant difference in ICDs between patients receiving dopaminergic medication and patients on DBS, whilst the case reports showed that 56% of patients undergoing DBS had poor outcome with regards to ICDs. We discuss these ambivalent findings in the light of proposed pathogenetic mechanisms. Longitudinal, prospective studies with larger number of patients are required in order to fully understand the role of DBS on ICDs in patients with PD.

Dopamine, Reward, and Frontostriatal Circuitry in Impulse Control Disorders in Parkinson's Disease: Insights from Functional Imaging

Dopamine agonists have been implicated in the development of impulse control disorders (ICDs). This may be due to the ability of agonists to tonically stimulate dopamine receptors. Recent neuroimaging data provided evidence that dopamine agonists induce significant changes in those frontostriatal circuits that process reward and mediate our ability to control impulses. Tonic stimulation of dopamine receptors via agonists may impair reward processing and inhibitory control mechanisms in ways that promote pathological repetition of behaviors. We will provide an overview of the current understanding of the neurobiology underlying ICDs in Parkinson's disease (PD).

The use of biofeedback, CES, brain mapping and neurofeedback with youth who have sexual behavior problems.

Introduction During the early part of this decade, an increasing number of researchers, practitioners, and clinicians, within the field of assessing and treating sexually abusive and sexually aggressive behavior, among others, have begun to address the impact of trauma on the brain, especially in young people with sexual behavior problems, Teicher (2007), Creeden, (2006), Bengis & Cunningam (2006). This information and knowledge also has direct application to those young people who also have histories of abuse and/or neglect, Ziegler, (2005), Ogden, Minton, & Pain, (2006). In particular the professionals listed above and others have addressed the impact on youth with sexual behavior problems and those who have been sexually abused. This is important because many young people with sexual behavior problems have a history of abuse and neglect. Teicher, (2008), notes that exposure to childhood abuse, particularly childhood sexual abuse, is a risk factor for development of impulse control disorders, and can lead to a cycle of violence and perpetration. Exposure to early stress can exert enduring effects on brain development that may underlie many of the consequences of exposure to sexual abuse. Research indicates there are negative effects of childhood sexual abuse on development of the hippocampus, corpus callosum, prefrontal cortex and visual cortex. Martin Kafka, MD, Clinical Associate Professor of Psychiatry at Harvard Medical School notes, that the following are risk factors for sexual recidivism in adult males: negative states, disorder, ADHD combined subtype, PTSD, Conduct Disorder, and BiPolar Dysthymic Disorder. Kafka notes that 10-15% of males with anxiety and/or depression had sexual risk taking behaviors; and that mood and anxiety disorders may be so common among sexual offenders, that these conditions and their associated effects are not distinctly identified as correlated with recidivism. Trauma and Its Impact on the Brain Trauma resulting from early childhood abuse and neglect impacts the brain in a variety of ways. The Training & Research Institute, Inc. in Albuquerque, NM (2004) notes that childhood physical, emotional, sexual abuse and neglect can cause antisocial behavior by over-excitation of the limbic system; the primitive midbrain region that regulates memory and emotion, and the prefrontal cortex; which is associated with judgment, consequential thinking, and moral reasoning. They note, for example: 1) The left hemisphere is responsible for regulation and oversight of logical responses to a situation; and control and mediation of emotional responses generated by the right hemisphere. The impact of childhood abuse or neglect results in diminished control of emotional response, resulting in poor or inappropriate reactions to emotional situations, angry outbursts, selfdestructive or suicidal impulses, paranoia, psychosis, and a tendency to pursue intense ultimately unstable relationships. 2) The prefrontal cortex is the internal editor of emotional states, consequential thinking, moral reasoning, and reactions to emotional crisis. The impact of childhood abuse or neglect results in increased potential for depression and delinquent and criminal behavior. 3) The corpus collosum creates communication between the right and left hemispheres. The impact of childhood abuse or neglect results in a significantly smaller corpus collosum, causing nonintegrated, inappropriate responses to everyday situations. 4) The temporal lobes regulate emotions and verbal memory. The impact of childhood abuse or neglect results in poor modulation of emotions, and an increased chance for temporal lobe epilepsy. 5) The hippocampus (part of the limbic system) is responsible for the formulation and retrieval of verbal and emotional memories. …

Long‐term follow‐up of impulse control disorders in Parkinson's disease

Recent studies have linked dopamine agonist (DA) usage with the development of impulse control disorders (ICDs) in Parkinson's disease (PD). Little is known about optimal management strategies or the long-term outcomes of affected patients. To report on the clinical interventions and long-term outcomes of PD patients who developed an ICD after DA initiation. Subjects contacted by telephone for a follow-up interview after a mean time period of 29.2 months. They were administered a modified Minnesota Impulse Disorder Interview for compulsive buying, gambling, and sexuality, and also self-rated changes in their ICD symptomatology. Baseline and follow-up dopamine replacement therapy use was recorded and verified by chart review. Of 18 subjects, 15 (83.3%) participated in the follow-up interview. At follow-up, patients were receiving a significantly lower DA levodopa equivalent daily dosage (LEDD) (Z = -3.1, P = 0.002) and a higher daily levodopa dosage (Z = -1.9, P = 0.05), but a similar total LEDD dosage (Z = -0.47, P = 0.64) with no changes in Unified Parkinson's Disease Rating Scale motor score (Z = -1.3, P = 0.19). As part of ICD management, 12 (80.0%) patients discontinued or significantly decreased DA treatment, all of whom experienced full or partial remission of ICD symptoms by self-report, and 10 (83.3%) of whom no longer met diagnostic criteria for an ICD. For PD patients who develop an ICD in the context of DA treatment, discontinuing or significantly decreasing DA exposure, even when offset by an increase in levodopa treatment, is associated with remission of or significant reduction in ICD behaviors without worsening in motor symptoms.