Pathways and Genetic Determinants of Impulse Control Disorders in Parkinson's Disease

Background: Impulse control disorders (ICDs) are a common non-motor complication in Parkinson's disease (PD) patients with multiple negative consequences for the individual and caregivers. Although ICDs are strongly linked to dopaminergic therapy, particularly dopamine agonists, only a percentage of patients develop these behaviors, suggesting the involvement of additional susceptibility factors, including genetic variability. This review aims to analyze current knowledge on the genetic background of ICDs. Methods: A literature search was conducted in the PubMed and Scopus databases for peer-reviewed research regarding the role of genetics in ICDs, published in the English language from 1996 to 2026. References of the selected articles for possible additional articles were also screened in order to include most of the key recent evidence. Genes that are involved in the dopaminergic system play a central role in ICD susceptibility, although the findings in studies are often inconsistent and not replicated. Moreover, variants in genes related to the glutamatergic (e.g., GRIN2B), serotonergic (e.g., HTR2A and TPH2), and opioid systems (e.g., OPRK1 and OPRM1) have been implicated, supporting a multi-system contribution to ICD pathophysiology. Conclusions: Early recognition of genetic factors that increase susceptibility to ICDs in PD patients is awaited to increase diagnostic accuracy and expedite individualized treatment.