Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Impulse control disorders such as pathological gambling (PG) are a serious and common adverse effect of dopamine (DA) replacement medication in Parkinson's disease (PD). Patients with PG have increased impulsivity and abnormalities in striatal DA, in common with behavioural and substance addictions in the non-PD population. To date, no studies have investigated the role of extrastriatal dopaminergic abnormalities in PD patients with PG. We used the PET radiotracer, [11C] FLB-457, with high-affinity for extrastriatal DA D2/3 receptors. 14 PD patients on DA agonists were imaged while they performed a gambling task involving real monetary reward and a control task. Trait impulsivity was measured with the Barratt Impulsivity Scale (BIS). Seven of the patients had a history of PG that developed subsequent to DA agonist medication. Change in [11C] FLB-457 binding potential (BP) during gambling was reduced in PD with PG patients in the midbrain, where D2/D3 receptors are dominated by autoreceptors. The degree of change in [11C] FLB-457 binding in this region correlated with impulsivity. In the cortex, [11C] FLB-457 BP was significantly greater in the anterior cingulate cortex (ACC) in PD patients with PG during the control task, and binding in this region was also correlated with impulsivity. Our findings provide the first evidence that PD patients with PG have dysfunctional activation of DA autoreceptors in the midbrain and low DA tone in the ACC. Thus, altered striatal and cortical DA homeostasis may incur vulnerability for the development of PG in PD, linked with the impulsive personality trait.
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PMID:Extrastriatal dopaminergic abnormalities of DA homeostasis in Parkinson's patients with medication-induced pathological gambling: a [11C] FLB-457 and PET study. 2276 31

Impulse control disorder during continuous subcutaneous apomorphine treatment (CAI) was recently reported. We describe a 54-year-old patient with familial Parkinson's disease, who after initiation of CAI in addition to high dose levodopa and amantadine, developed impulse control disorder (major financial loss related to risky transactions and self-medication), psychosis and depression, which lead up to attempted suicide. To our knowledge, this is the first case of attempted suicide under apomorphine treatment.
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PMID:Attempted suicide under high dose dopaminergic therapy including apomorphine. 2279 6

In patients with Parkinson's disease, aberrant or excessive dopaminergic stimulation is commonly indicated as the trigger factor in unmasking impulse control disorders (ICDs) such as pathological gambling. We had the opportunity to follow a patient who experienced Parkinson's disease 7 years ago when he was using pramipexole and again, recently, when he was treated with levodopa (L-dopa) and low frequency stimulation of the nucleus of the pedunculopontine tegmentus (PPTg) but no dopamine agonists. The same patient had shown, when studied with fluorodeoxyglucose-positron emission tomography in the condition PPTg-ON, a peculiar increased activity in the left ventral striatum. This case report confirms that, in a predisposed personality, ICD may arise from the perturbation of endogenous pathways, which connect the brainstem to the basal ganglia.
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PMID:Pathological gambling from dopamine agonist and deep brain stimulation of the nucleus tegmenti pedunculopontine. 2279 81

Parkinson's disease (PD) is associated with a number of behavioral disorders which may cause considerable social, professional or financial problems. Impulse control disorders (ICDs), such as pathological gambling, binge eating, compulsive shopping and hypersexuality occur in approximately 13-14% of PD patients. Further behavioral disorders are the dopamine dysregulation syndrome (DDS), a substance dependence characterized by craving for dopaminergic substances and punding (prolonged repetitive activities which are not goal-oriented).Treatment-related risk factors are dopamine agonists for ICDs and a high total dopaminergic dose for DDS and punding. Shared risk factors are young age at onset, impulsive personality traits, depression and possibly dyskinesia. At the neuronal level these behavioral disorders seem to be associated with changes in the reward system and dysfunction of the orbitofrontal cortex. The evidence level for management strategies is at present insufficient. For ICDs current clinical practice consists of discontinuation or reduction of dopamine agonists.
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PMID:[Repetitive impulse-associated behavioral disorders in Parkinson's disease]. 2287 76

Impulse control and repetitive behavior disorders (ICRBs) are a group of diseases including impulse control disorder (ICD), repetitive behavior disorder (RB), and dopamine dysregulation syndrome (DDS). This study determined the prevalence and associated characteristics of ICRBs in Parkinson's disease (PD) patients. Included were 297 patients, interviewed with the questionnaire for impulsive-compulsive disorders in PD for screening of various ICRBs. Questionnaire results and clinical characteristics were analyzed. The ICRB prevalence among PD patients was 15.5 % (46 of 297), with 35 patients with ICD, 20 with RB, and 7 with DDS. Patients with ICRB were predominantly male, younger, taking higher doses of dopaminergic drugs, and had longer disease duration, worse Unified Parkinson's Disease Rating Scale (UPDRS) motor score, and worse PD quality of life questionnaire score. However, each ICRB subtype had different risk factor profiles. ICD patients were predominantly male, younger, had longer disease duration, were affected by PD from young age, were taking higher total dopaminergic drug dosages, and had more RB. RB patients had higher UPDRS part III scores, were taking higher levodopa doses, and had higher comorbid ICD. DDS patients were taking higher dopamine agonist doses, and had more frequent ICD. In multivariate logistic regression for secondary analysis, only younger age and comorbid RB or DDS showed significant association with ICD and only poor UPDRS III score and comorbid ICD were significantly associated with RB. These findings suggested that different risk factors contribute to development of each ICRB subtype. ICRB could be a combination of heterogeneous disease entities that need to be treated separately.
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PMID:Clinical characteristics of impulse control and repetitive behavior disorders in Parkinson's disease. 2289 7

Impulse control disorders (ICDs), such as compulsive gambling, buying, sexual behavior, and eating, are a serious and increasingly recognized complication of dopamine replacement therapy in Parkinson's disease (PD). Other impulsive-compulsive behaviors have been linked to dopaminergic medications; these include punding (stereotyped, repetitive, purposeless behaviors) and dopamine dysregulation syndrome (DDS; compulsive medication overuse). ICDs have been most closely related to the use of dopamine agonists (DAs), particularly at higher dosages; in contrast, DDS is primarily associated with shorter-acting, higher-potency dopaminergic medications, such as apomorphine and levodopa. Risk factors for ICDs may include male sex; younger age; younger age at PD onset; a pre-PD history of ICD(s); personal or family history of substance abuse; bipolar disorder; gambling problems; and impulsive personality traits. The primary treatment of ICDs in PD is discontinuation of DA therapy. Not all patients can tolerate this, however, due to worsening motor symptoms and/or DA withdrawal syndrome (a severe, stereotyped drug withdrawal syndrome similar to that of other psychostimulants). While psychiatric medications are frequently used to treat ICDs in the general population, there is no empirical evidence to suggest that they are effective in PD. Given the paucity of treatment options and potentially serious consequences of ICDs in PD, it is critical for patients to be monitored closely for their development. As empirically validated treatments for ICDs emerge, it will also be important to examine their efficacy and tolerability in individuals with comorbid PD.
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PMID:Impulse control and related disorders in Parkinson's disease. 2303 8

Impulse control disorders (ICDs) are frequent in Parkinson's disease (PD). Aim of the present study was to investigate cognition and behaviour in PD patients with and without ICDs, in order to identify potential early clinical features which might be associated to the development of ICDs. We recruited 17 PD patients with ICDs and 17 without ICDs, matched for several clinical variables, without clinically significant cognitive deficits. Assessments included behavioural scales and a neuropsychological battery, including the Iowa Gambling Task (IGT). In patients with ICDs, the total score of the BIS and the Motor Impulsivity subscore were significantly higher than in patients without ICDs. In patients with ICDs, we observed only statistical trends towards a worse performance on neuropsychological tasks (go-no-go subtest of the Frontal Assessment Battery, oral verb naming task, copying of drawings with landmarks) sensitive to frontal lobe dysfunction (FLD) and on the IGT (loss of a greater amount of money, more risky choices). As compared to patients without ICDs, they reported a more than threefold number of errors on the interference subtest of Stroop test, which is also sensitive to FLD. Although this study did not show any significant difference between PD patients presenting ICDs as compared with patients without ICDs on neuropsychological variables, some preliminary evidence was detected suggesting a trend toward a worse performance of the PD-ICD group on few neuropsychological tasks which are at least partially sensitive to frontal lobe dysfunction, including tasks sensitive to dysfunction of ventral fronto-striatal loops.
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PMID:Neuropsychological features of patients with Parkinson's disease and impulse control disorders. 2351 19

Impulse control disorders (ICD) have been recognised in Parkinson's disease (PD) as adverse effects of dopamine replacement therapy, particularly with dopamine agonists. Although virtually all PD patients are treated with dopaminergic drugs, only a minority will develop hyperdopaminergic states, suggesting predisposing and/or protecting factors. The age at onset, the sex and the dose or type of dopaminergic drugs have been identified as clinical predictive factors. Recent genetic studies have investigated associations between ICD and polymorphisms of genes involved in the dopamine metabolism pathway (COMT, DAT), dopamine receptors (DRD1, DRD2, DRD3, DRD4), serotonin receptors and its transporter (HTR2A, 5HTT), and glutamate receptors (GRIN2B). Although validation in larger and independent cohorts is needed, the results from these studies give us some insights into the pathophysiology of hyperdopaminergic states and may be useful, at term, in personalising antiparkinsonian treatment in clinical practice.
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PMID:Genetics of impulse control disorders in Parkinson's disease. 2323 65

Non-motor symptoms contribute significantly to Parkinson's disease (PD) related disability. Impulse control disorders (ICDs) have been recently added to the behavioural spectrum of PD-related non-motor symptoms. Such behaviours are characterized by an inappropriate drive to conduct repetitive behaviours that are usually socially inadequate or result in harmful consequences. Parkinson disease impulse control disorders (PD-ICDs) have raised significant interest in the scientific and medical community, not only because of their incapacitating nature, but also because they may represent a valid model of ICDs beyond PD and a means to study the physiology of drive, impulse control and compulsive actions in the normal brain. In this review, we discuss some unresolved issues regarding PD-ICDs, including the association with psychiatric co-morbidities such as obsessive-compulsive disorder and with dopamine related side effects, such as hallucinations and dyskinesias; the relationship with executive cognitive dysfunction; and the neural underpinnings of ICDs in PD. We also discuss the contribution of neuroscience studies based on animal-models towards a mechanistic explanation of the development of PD-ICDs, specifically regarding corticostriatal control of goal directed and habitual actions.
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PMID:Impulse control disorders in Parkinson's disease: crossroads between neurology, psychiatry and neuroscience. 2324 59

Parkinson's disease (PD) is traditionally viewed as a motor disorder with a characteristic triad of tremor, rigidity and bradykinesia. There is now increasing awareness that PD is a complex systemic disorder with many nonmotor symptoms (NMS) which include autonomic dysfunction, sleep disorders, sensory and neuropsychiatric features. NMS become more common in severity and frequency with advancing disease when neuropsychiatric features such as cognitive impairment and psychosis dominate the clinical picture. NMS are strongly correlated with quality of life for patients and their families as well as institutional care placement. Despite their importance, NMS are poorly recognized by clinicians and often undeclared by patients. Use of a validated screening tool NMSQuest followed by specific symptom assessment instruments strengthens the recognition and holistic management of NMS in PD. Some NMS such as mood disturbance, anxiety, pain and insomnia may be improved by optimization of dopaminergic therapy. Conversely, psychosis, excess daytime somnolence or impulse control disorder (ICD) may be triggered by dopaminergic drugs. Other NMS such as dementia and severe depression may be unresponsive to dopaminergic treatment and may reflect perturbations in cholinergic, serotonergic or noradrenergic neurotransmitter function. These symptoms are more challenging to manage but may be ameliorated to some extent by agents such as acetylcholinesterase inhibitor or antidepressant drugs. This contribution reviews the evidence for the evaluation and management of key NMS in PD (apathy, anxiety, depression, psychosis, dementia, ICD, sleep disturbance, autonomic dysfunction, pain) and highlights the urgent need for both novel therapies and more controlled trials for current therapeutic strategies.
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PMID:Evaluation and management of the non-motor features of Parkinson's disease. 2325 43


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