Neurobiology and clinical features of impulse control failure in Parkinson's disease

Impulse control disorders (ICDs) and other impulsive-compulsive related behaviours are frequent and still under recognized non-motor complications of Parkinson's disease (PD). They result from sensitization of the mesocorticolimbic pathway that arose in predisposed PD patients concomitantly with spreading of PD pathology, non-physiological dopaminergic and pulsatile administration of dopamine replacement therapy (DRT). Neuropsychiatric fluctuations (NPF) reflect the psychotropic effects of dopaminergic drugs and play a crucial role in the emergence of ICDs and behavioral addictions. Dopamine agonists (DA) which selectively target D2 and D3 receptors mostly expressed within the mesocorticolimbic pathway, are the main risk factor to develop ICDs. Neuroimaging studies suggest that dopamine agonists lead to a blunted response of the brain's reward system both during reward delivery and anticipation. Genetic predispositions are crucial for the responsiveness of the mesolimbic system and the development of ICDs with several genes having been identified. Early screening for neuropsychiatric fluctuations, reduction of DA, fractionating levodopa dosage, education of patients and their relatives, are the key strategies for diagnosis and management of ICDs and related disorders.