Pathophysiology Of Impulse Control Disorders Research Articles

Drug Treatment of Trichotillomania (Hair-Pulling Disorder), Excoriation (Skin-picking) Disorder, and Nail-biting (Onychophagia).

BackgroundTrichotillomania (TTM), excoriation (or skin-picking) disorder and some severe forms of onychophagia are classified under obsessive-compulsive and related disorders. There are different interacting neurotransmitter systems involved in the pathophysiology of impulse-control disorders, implicating noradrenaline, serotonin, dopamine, opioid peptides and glutamate, hence investigators focused on drugs able to act on these transmitters. Our aim was to critically review the efficacy of the drugs employed in impulse-control disorders.MethodsWe searched for controlled drug trials to treat TTM, excoriation, and/or nail-biting six databases (PubMed, Cochrane, Scopus, CINAHL, PsycINFO/PsycARTICLES, and Web of Science), using the search strategy: (trichotillomania OR “excoriation disorder” OR “face picking” OR “skin picking” OR “hair pulling” OR onychophagia OR “nail-biting”) AND drug treatment on 12 March 2018 for all databases. We followed in our method of identifying relevant literature the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.ResultsSSRIs and clomipramine are considered first-line in TTM. In addition, family members of TTM patients are often affected by obsessive-compulsive spectrum disorders. Other drugs used in the treatment of TTM are lamotrigine, olanzapine, N-Acetylcysteine, inositol, and naltrexone.ConclusionThe treatment of TTM, excoriation disorder and nail-biting is still rather disappointing. Conjectures made from preclinical studies and the relative pathophysiological hypotheses found poor confirmations at a clinical level. There is a need for further studies and the integration of pharmacological and psychotherapeutic. Our results point to the need of integrating personalised medicine principles in the treatment of these patients.

The pathophysiology of impulse control disorders in Parkinson disease.

Aims: This review aims to evaluate the most recent evidence on the pathophysiology of impulse control disorders (ICDs) in Parkinson disease (PD). Methods: Computerised searches of Medline, Embase and PsycInfo, along with manual searches for grey literature, were conducted and resulted in a total of 16 studies suitable for review. Results: Evidence was divided into four categories: medication used in PD management, imaging studies, genetic analysis and subthalamic deep brain stimulation (STN-DBS). Analysis of the literature reveals that both intrinsic and extrinsic factors may play a role in the pathophysiology of ICDs in PD. Dysfunction of the mesocorticolimbic pathway and polymorphisms of the dopamine D3 and D4 receptors may increase an individual's susceptibility to the development of ICDs. Discussion: Dopaminergic medication, particularly dopamine agonists (DAs), increases the risk of developing impulsive behaviours in a PD patient. Further evidence, particularly in the form of prospective studies and randomised controlled trials is required to better establish the pathophysiology of ICDs in PD.

The Pathophysiology of Impulse control Disorders in Parkinson Disease

The Pathophysiology of Impulse control Disorders in Parkinson Disease

Impulse control disorders in Parkinson's disease

The aim is to review the recent advances in the epidemiology and pathophysiology of impulse control disorders (ICDs) in Parkinson's disease. Large cross-sectional and case-control multicentre studies show that ICDs in Parkinson's disease are common, with a frequency of 13.6%. These behaviours are associated with impaired functioning and with depressive, anxiety and obsessive symptoms, novelty seeking and impulsivity. Behavioural subtypes demonstrate differences in novelty seeking and impulsivity, suggesting pathophysiological differences. Observational and neurophysiological studies point towards a potential mechanistic overlap between behavioural (ICDs) and motor (dyskinesias) dopaminergic sequelae. Converging data suggest dopamine agonists in ICDs appear to enhance learning from rewarding outcomes and impulsive choice. ICD patients also have enhanced risk preference and impaired working memory. Neuroimaging data point towards enhanced bottom-up ventral striatal dopamine release to incentive cues, gambling tasks and reward prediction, and possible inhibition of top-down orbitofrontal influences. Dopamine agonist-related ventral striatal hypoactivity to risk is consistent with impaired risk evaluation. Recent large-scale studies and converging findings are beginning to provide an understanding of mechanisms underlying ICDs in Parkinson's disease, which can guide prevention of these behaviours and optimize therapeutic approaches.

A2A Adenosine Receptor Binding Parameters in Platelets from Patients Affected by Pathological Gambling

Background/Aims: A structural and functional interaction between A_2A adenosine receptors and D₂ dopamine receptors has been implicated in the pathophysiology of impulse control disorders. The aim of this study was to use platelet membranes to assess A_2A adenosine receptor affinity and density in patients affected by pathological gambling (PG; which is classified as a specific impulse control disorder) with respect to those of control subjects. Methods: Twelve drug-free PG patients and 12 age- and sex-matched healthy controls were enrolled in the study. PG was diagnosed according to the Structured Clinical Interview for DSM-IV – Patient Version 2.0 and the South Oaks Gambling Screen. A_2A adenosine receptor binding parameters were evaluated using a [³H]ZM₂₄₁₃₈₅ binding assay; affinity and density (B_max) were determined by means of saturation binding studies with platelet membranes. Results: The A_2A adenosine receptor binding affinity was found to be significantly higher in patients affected by PG than in healthy subjects; in contrast, no significant differences in B_max were observed between the 2 groups. Conclusions: The elevated A_2A adenosine receptor binding affinity in platelets from PG patients with respect to control subjects demonstrates for the first time a change in adenosine receptor parameters, and it suggests the involvement of the adenosine system in this pathology. The previously demonstrated hyperactivity of the dopamine system in PG may modulate the A_2A adenosine receptor, supporting a role for this receptor as a peripheral marker of dopamine dysfunction. Because it is not possible to directly measure the D₂ dopamine receptor in human platelets, these data are particularly relevant to the detection of dopamine dysfunction.

Frontal–striatal abnormalities underlying behaviours in the compulsive–impulsive spectrum

In this paper, we tentatively bring together the psychiatric, neurological and addiction perspectives on the impulsive–compulsive spectrum of neuropsychiatric disorders, in order to understand the pathophysiology of impulse control disorders (ICDs) in Parkinson's disease. In an attempt to try to pool the various levels of information we will therefore focus on three disorders within the impulse-compulsive spectrum, i.e., obsessive–compulsive disorder (OCD), ICDs in Parkinson's disease, and cocaine seeking behaviour. Whereas there are large differences between these three domains, each with their own nomenclature, hypotheses and study results, they share the focus on an imbalance within and between the frontal–striatal circuits as underlying substrate for the behaviours. For each disorder, we summarize the results from recent studies in order to describe in which way alterations in the frontal–striatal circuits contribute to the phenotype. The phenomenological overlap between ICDs in Parkinson's disease, addiction and OCD needs further investigation, since better understanding of the overlapping and differentiating characteristics will contribute to our understanding of the pathophysiology of the disturbances and treatment alternatives.

Selective Dopamine D3 Receptor Antagonists: A Review 2001-2005

A growing body of evidence indicates that dopamine (DA) D(3) receptors are significantly involved in the control of drug-seeking behavior, and may play an important role in the pathophysiology of impulse control disorders and schizophrenia. This hypothesis has been difficult to test due to the lack of compounds with high selectivity for central DA D(3) receptors. Recently, however, the synthesis and characterization of new highly potent and selective DA D(3) receptor antagonists has permitted to characterize the role of the DA D(3) receptor in a wide range of preclinical animal models. Although the proof of efficacy of pharmacotherapeutic agents is to be derived ultimately from clinical trials, the preclinical findings that selective antagonism at DA D(3) receptors reduces the reinforcing efficacy of drugs of abuse, reverses cognitive deficits, and shows efficacy in animal models of schizophrenia add to an accumulating body of evidence that selective DA D(3) receptor antagonists may hold highest promise in the treatment of several neuropsychiatric diseases. The present review is aiming at describing current areas of interest and the possible future development of selective DA D(3) receptor antagonists by outlining about 40 patents and 100 publications in this research field between 2001 and 2005.