A review.Impulse control disorders (ICDs) are a spectrum of behaviors characterized by an inability to resist the urge to engage in self-destructive or risky behaviors.In Parkinson's disease (PD), replacement therapy with a Dopamine agonist (DA) is a significant risk factor for developing ICDs.However, not all patients are affected, and the severity varies widely, suggesting a complex background.Several genetic polymorphisms that affect reward mechanisms and risky behaviors have been proposed as potential factors in the development of ICD.These polymorphisms are found in genes involved in various neurotransmitter systems, particularly in the dopaminergic system (DRD1, DRD2, DRD3, DRD4), the catechol-O-methyltransferase (COMT), and dopamine transporter (DAT).Other systems such as norepinephrine, serotonin (HTR2A), glutamate (GRIN2B), opioid (OPRM1, ORPK1), and the serotonin metabolism enzyme tryptophan hydroxylase (TPH2) have also been implicated in susceptibility to ICD.From this perspective, the bench-to-bedside approach for the clinician would be to obtain DNA genotyping in routine visits, inform patients of their risk profile, and make decisions regarding PD medication accordingly.Other tools are also being evaluated to detect differences before the onset of ICD through imaging techniques, such as functional magnetic resonance imaging (fMRI).In conclusion, recent studies exploring the prediction of impulse control in PD are certainly encouraging.Neurophysiol., imaging, and genetic studies may provide valuable insights as biomarkers.However, there is no single fool-proof formula to accurately predict ICD-PD.

17 May 2023·The Journal of Clinical Endocrinology & Metabolism

A Genetic Assessment of Dopamine Agonist-Induced Impulse Control Disorder in Patients With Prolactinoma

Article

Author: Poyraz, Burc Cagri ; Sayitoglu, Muge ; Kadioglu, Pinar ; Ozkaya, Hande Mefkure ; Özogul, Yeliz Yagiz ; Durcan, Emre ; Sahin, Serdar ; Sudutan, Tugce ; Kavla, Yasin

AbstractContextDopamine agonist (DA)–induced impulse control disorder (ICD) represents a group of behavioral disorders that are increasingly recognized in patients with prolactinoma.ObjectiveWe aimed to examine the genetic component of the underlying mechanism of DA-induced ICD.MethodsPatients with prolactinoma receiving dopamine agonist (cabergoline) treatment were included in the study. These patients were divided into 2 groups: patients who developed ICD due to DA and patients who did not. Patients were evaluated for polymorphisms of the DRD1, DRD3, COMT, DDC, GRIN2B, TPH2, OPRK1, OPRM1, SLC6A4, SLC6A3, HTR2A genes.ResultsOf the 72 patients with prolactinoma using cabergoline, 20 were diagnosed with ICD. When patients with and without ICD were compared according to genotype frequencies, OPRK1/rs702764, DRD3/rs6280, HTR2A/rs6313, SLC6A4/rs7224199, GRIN2B/rs7301328, TPH2/rs7305115, COMT/rs4680, DRD1/rs4532 polymorphisms significantly increased in patients with DA-induced ICD.ConclusionOur results show that multiple neurotransmission systems affect DA-induced ICD in patients with prolactinoma.

01 Feb 2022·Brain Imaging and BehaviorQ2 · MEDICINE

Prefrontal and striatal dopamine D2/D3 receptors correlate with fMRI BOLD activation during stopping

Q2 · MEDICINE

Article

Author: Schreckenberger, Mathias ; Tüscher, Oliver ; Sebastian, Alexandra ; Pfeifer, Philippe ; Buchholz, Hans Georg ; Gründer, Gerhard ; Fehr, Christoph ; Kaller, Christoph P

AbstractD2-like dopamine receptors in animals and humans have been shown to be linked to impulsive behaviors that are highly relevant for several psychiatric disorders. Here, we investigate the relationship between the fronto-striatal D2/D3 dopamine receptor availability and response inhibition in a selected population of healthy OPRM1 G-allele carriers. Twenty-two participants successively underwent blood-oxygen level dependent functional magnetic resonance imaging (fMRI) while performing a stop-signal task and a separate positron emission tomography (PET) scan. Striatal and extrastriatal D2/D3 dopamine receptor availability was measured using the radiotracer [18F]fallypride. Caudate D2/D3 dopamine receptor availability positively correlated with stopping-related fronto-striatal fMRI activation. In addition, right prefrontal D2/D3 dopamine receptor availability correlated positively with stopping-related striatal fMRI BOLD signal. Our study partially replicates previous findings on correlations between striatal D2/D3 dopamine receptor availability and response inhibition in a population selected for its genetic determination of dopamine response to alcohol and as a modulator of impulse control via the endogenous opioid system. We confirm the important role of D2/D3 dopamine receptor availability in the fronto-striatal neural circuit for response inhibition. Moreover, we extend previous findings suggesting that dopamine receptor availability in the right inferior frontal cortex, a crucial region of the stopping network, is also strongly associated with stopping-related striatal fMRI activity in healthy OPRM1 G-allele carriers.

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