Study Examines Risk Factors for Impulse Control Disorders in Parkinson’s Patients

Use of dopamine agonists, earlier disease onset, being male, and having personality traits such as impulsiveness and high novelty-seeking are among the risk factors for developing impulse control disorders (ICDs) in people with Parkinson’s, according to a review study.

The research, “Impulse control disorders in Parkinson’s disease: A systematic review on risk factors and pathophysiology,” was published in the Journal of the Neurological Sciences.

ICDs are characterized by failure to resist an impulse, drive, or temptation to perform a risky behavior, a growing sense of tension before performing the behavior, and a sense of pleasure while doing it.

In people with Parkinson’s, ICDs may result from treatments intending to increase the levels of dopamine in the brain. Despite their impact on patients’ quality of life, studies about ICDs in this patient population are scarce.

Aiming to address this gap, a research team from IRCCS Centro Neurolesi “Bonino Pulejo”, in Italy, conducted a systematic review of the potential risk factors for the development of ICDs in people with Parkinson’s, including the effects of dopaminergic treatment. Three online databases were used covering studies published from January 2000 to July 2018.

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According to research published in 2003 and 2008, the prevalence of gambling, compulsive sexual behavior, and compulsive shopping is 1.7-7.0%, 2.0–4.0%, and 0.4-3.0%, respectively. The 2003 study found one or more ICDs in 13.6% of patients, which included binge eating and hypersexuality. Recent epidemiological studies have indicated that the prevalence of ICDs is 7.2% in patients with Parkinson’s, but only 1% in controls (participants who did not have Parkinson’s.

Specifically, for example, although binge eating typically leads to weight gain, people with Parkinson’s commonly lose weight, which is attributed to swallowing difficulties (dysphagia) and dyskinesia (involuntary, jerky movements).

Slot machine gambling has been identified as the most common form of pathological gambling among these patients. Major depression in middle-aged men has been reported as a comorbidity of pathological gambling, with common genetic factors.

Patients also have an increased risk of developing dopamine dysregulation syndrome, which results from unregulated self-administration and dependence on dopaminergic treatment. “Patients increase drugs doses spontaneously and progressively and this is often associated to behavioral and mood disorders, such as hallucinations, manic states, aggression, psychomotor agitation and delusions,” researchers explained.

Developing addiction-like behavior has been associated with the type, dose and duration of dopaminergic treatment, in particular dopamine agonists.

A 2006 study showed a correlation between earlier onset of Parkinson’s and earlier appearance of motor fluctuations, dyskinesia and psychiatric symptoms. Also, a study with 3,090 patients indicated that greater impulsive choice, faster reaction time and impulsive decisions are among the potential factors for the development of ICDs, although Parkinson’s patients are thought to have increased caution and be risk-averse prior to diagnosis.

Comparing to women, men not only have higher frequency of ICDs, but also show six-times greater difficulty managing them, as shown in a 2012 study. Other factors shown to associate with ICDs in Parkinson’s include sleep impairment, substance abuse, high novelty-seeking, impulsiveness, aggressiveness, cigarette smoking, having more formal education, and being unmarried.

As for brain pathways underlying the development of ICDs, dysregulation of the mesolimbic circuit (responsible for reward learning and the mesocortical pathway (responsible for executive decision-making) leads to impulsive and compulsive behaviors.

Upon exposure to a reward, a brain area called the ventral striatum is activated, prompting a strong emotional response and dopamine release. This behavior ultimately may become compulsive, being reinforced by the dorsal striatum.

Two types of dopamine receptors — D1 and D2 — are involved in the connections between the striatum and the globus pallidus (a part of the brain’s basal ganglia) and subsequently the substantia nigra, a major brain region involved in Parkinson’s disease.

These receptors, and their pathways, have opposing roles in reward-based decision making, either stimulation (D1) or suppression (D2).

The researchers noted that standardized tests to evaluate the type and severity of ICDs are still lacking. Also, consistent use of international criteria for Parkinson’s diagnosis and prospective studies with larger samples are still needed to more accurately determine risk factors for ICDs among these patients.

“A better assessment of the behavioral disorders of [Parkinson’s] may be useful in the rehabilitative intervention for increasing the quality of life,” researchers concluded.