Pathological gambling in Parkinson's disease: disease related or drug related?

Pathological gambling and other impulse-control disorders occur in susceptible Parkinson's disease patients during dopaminergic therapy, particularly in association with dopamine agonists. Additional factors such as age at onset play an important role, and predisposing personality traits have been identified both in treated patients, as well as in patients even before therapy is initiated. The contributions of specific allelic polymorphisms of the dopamine receptor and transporter genes were also tested as predictors of adverse effects of dopaminergic therapy but results are not conclusive. Recent imaging studies have shed light on the mechanism underlying pathological gambling. Resting-state brain perfusion of Parkinson's disease gamblers showed higher activity in 'limbic' areas associated with addictive processes. More importantly, severity of this behavior is associated with the impaired functioning of brain regions that are involved in 'top-down' cognitive monitoring and inhibition of inappropriate behaviors. This evidence is consistent with a significant contribution of disease-related factors.