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

doi:10.1016/j.parkreldis.2011.10.019

Parkinsonism & Related Disorders

Volume 18, Issue 4, May 2012, Pages 397-399

https://doi.org/10.1016/j.parkreldis.2011.10.019 Get rights and content

Abstract

Background

The 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.

Method

We 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.

Results

Genotyping was performed for variants of the DRD2 Taq1A (rs1800497), COMT Val¹⁵⁸Met (rs4680), DAT1 (3′ UTR 40 bp VNTR). Variants of DRD2 Taq1A, COMT and DAT1 were not associated with the risk of developing ICDs.

Conclusion

In 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.

Section snippets

Background

The mechanisms underlying the development of impulse control disorders (ICDs) like compulsive gambling, buying, sexual, and eating behaviors in Parkinson’s disease (PD) are debated. ICDs commonly develop after the initiation of dopaminergic therapy but predisposing behavioral traits have been recently reported also in newly diagnosed “de novo” patients [1]. Risk factors are use of dopamine agonists as well as novelty-seeking personality, impulsivity, and family history of alcohol use disorders

Subjects and data collection

In this case control study, PD patients were enrolled from the Parkinson’s disease Centre of the “San Camillo” Hospital (Venice Lido, Italy) and the Neurology Department at the University of Padua. We only included idiopathic PD patients diagnosed according to the United Kingdom Parkinson’s disease Society brain bank. ICDs were diagnosed according to the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders Text Revision criteria [8]. According to a previously published

Results

A total of 89 PD patients was enrolled in the study, 41 classified as ICD positive (Table 1). ICD patients were younger and had earlier age at onset compared with control PD. There was trend for both higher levodopa and dopamine agonist dose in ICD positive patients. There was also a trend for ICD to be more frequent in patients on COMT inhibitors (21 out of 41; 52% vs. 11 out of 48 in the ICD negative group).

The allelic frequencies for the three polymorphisms studied in PD with and without

Discussion

The development of ICDs in PD may be related to abnormal signaling and transmission in the dopaminergic pathway. In PD, excessive extra-synaptic dopamine, impaired reuptake of dopamine, or abnormal post-synaptic dopamine receptor stimulation and transmission by dopamine agonists may contribute to the development of these disturbances [11]. Evidence in favor of this hypothesis come from studies in alcohol dependence.

Two limiting factors of dopamine activity are the COMT and DAT which terminate

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Cited by (60)

Molecular Imaging of Addictive Behavior in Idiopathic Parkinson's Disease
2018, International Review of Neurobiology
Citation Excerpt :
The authors revealed that this genetic variant is associated with ICDs in PD patients receiving dopamine replacement therapy, primarily under low-dopaminergic-dose conditions (Lee et al., 2012). Unlike the general population, there was no relation observed to the dopamine D2 receptor, the CO-methyltransferase, or the serotonin transporter, a finding in line with an independent study performed in 41 PD patients with ICD with 48 matched controls (Vallelunga et al., 2012). Nevertheless, limitations of these investigations such as small sample size and the lack of replication does not allow for definitive conclusions.
Parkinson's disease (PD) is commonly associated with motor symptoms, however cognitive and neurobehavioral complications are increasingly recognized and contribute to long-term disability. Dopamine replacement therapy is effective for motor symptoms, but can also lead to motor side-effects and addictive behavior such as impulse control disorders. Molecular imaging is advancing our knowledge of the mechanisms involved in the development of behavioral addictions. This chapter will discuss potential risk factors and associations with the development of addictive behavior in PD including the role of dopaminergic medication and genetic predisposition. We further will describe the common neurobiology and similarities of addictive behavior in PD to addiction, particularly the neuroanatomy of reward processing and its alteration in substance and behavioral addictions. Finally, we will discuss molecular imaging approaches which are helping to delineate the structure as well as the dynamic interactions between different components involving neurotransmitters, transporters, and receptors.
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To investigate intrinsic neural networks connectivity changes in Parkinson's disease (PD) patients with and without impulse control disorders (ICD).
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The presence of ICD symptoms was associated with an increased connectivity within the salience and default-mode networks, as well as with a decreased connectivity within the central executive network (p < .05 corrected). ICD severity was correlated with both salience and default mode networks connectivity changes only in the ICD+ group. VBM analysis did not reveal any statistically significant differences in local grey matter volume between ICD+ and ICD− patients and between all patients and HC (p < .05. FWE).
The presence of a disrupted connectivity within the three core neurocognitive networks may be considered as a potential neural correlate of ICD presence in patients with PD. Our findings provide additional insights into the mechanisms underlying ICD in PD, confirming the crucial role of an abnormal prefrontal-limbic-striatal homeostasis in their development.
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Short communicationRole of genetic polymorphisms of the dopaminergic system in Parkinson’s disease patients with impulse control disorders

Abstract

Background

Method

Results

Conclusion

Section snippets

Background

Subjects and data collection

Results

Discussion

Parkinsonism Relat Disord

Biochem Pharmacol

Neuroimage

J Psychiatr Res

Alcohol

Impulsivity and compulsivity in drug-naïve patients with Parkinson’s disease

Mov Disord

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