Certain Genetic Variants Linked to Risk of Compulsive Behaviors in Parkinson’s Patients, Study Reports

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by Alice Melão |

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Manus Neurodynamica

Mutations in four specific genes may help to identify those Parkinson’s patients at risk of developing the addictive behaviors known as impulse control disorders, researchers report.

Their study, “Dopaminergic and Opioid Pathways Associated with Impulse Control Disorders in Parkinson’s Disease,” was published in Frontiers in Neurology.

People with Parkinson’s are more likely than others — at a threefold higher risk, in fact — of developing such disorders, and the compulsive behaviors related to a lack of control over activities that range from gambling and sexual activity to eating, shopping and hobbies.

Patients with impulse control disorders may also show an addiction-like pattern of dopaminergic medication use, the study reports.

Treatment with dopaminergic replacement therapies, such as Mirapex (pramipexole) and Requip (ropinirole), are considered a risk factor for impulse control disorders in this patient population.

But not all patients using these therapies develop compulsive behaviors, indicating that some are more susceptible than others.

Previous studies have suggested that genetics plays a role in this risk, with specific genes proposed to be linked to disorder susceptibility.

Indeed, research estimates that common genetic variants could account for about 57% of the variability reported in the incidence of compulsive behaviors among Parkinson’s patients.

Researchers in Norway analyzed genetic data on 119 Parkinson’s patients who met study requirements and were enrolled in the Norwegian ParkWest study — a population-based study of incident Parkinson’s in newly diagnosed patients and healthy controls.

Among patients, 29.4% had at least one impulse control disorder and 63% were taking dopamine agonist medications, whose use was linked to a 4.5 higher risk of an impulse control disorder.

A total of 16 genes were analyzed, all known to be involved in nerve cell communication and signaling pathways, as well as in mechanisms linked to impulse control disorders and related behaviors.

Eleven genetic variants — or changes in a gene’s DNA — evident in these genes were significantly associated with impulse control disorders. In particular, an alteration in the DRD1 gene (which encodes the dopamine receptor D1) was associated with 2.9 times higher risk of developing  such disorders.

Other genetic variants, such as those in the OPRK1 gene (which encodes the kappa-opioid receptor 1), were found to have a protective role.

Adding the genetic status of four genes — DRD1, OPRK1, OPRM1 and COMT — to patients’ age and dopamine agonist use further improved (by 13%) the research team’s ability to identify those at risk of developing impulse control disorders.

“These results confirm and expand existing knowledge about the genetic architecture of impulse control disorders in Parkinson’s disease,” the researchers wrote.

“Our findings demonstrate that a genetic panel [based on DRD1, OPRK1, OPRM1, and COMT] can provide valuable information with regard to the clinical differentiation between Parkinson’s patients at risk of impulse control disorders and patients without risk,” they added.