Depression and impulse control disorders in Parkinson's disease: Two sides of the same coin?

•Depression in Parkinson's disease (PD) is associated with reduced limbic activity.•Impulse control disorders (ICD) in PD are associated with increased limbic activity.•Depression and ICD in PD frequently coincide suggesting a common pathophysiology.•Reward-related ventral striatal dopamine release is important for both disorders.•Ventral striatal dopamine denervation might be a common neurobiological substrate.

Depression and impulse control disorders (ICD) are two common neuropsychiatric features in Parkinson's disease (PD). Studies have revealed that both phenomena are associated with aberrations in ventral striatal dopamine signaling and concomitant dysfunction of the reward-related (limbic) cortico-striatal–thalamocortical (CSTC) circuit. Depression in PD seems associated with decreased activity in the limbic CSTC circuit, whereas ICD seem associated with increased limbic CSTC circuit activity, usually after commencing dopamine replacement therapy (DRT). Not all DRT using PD patients, however, develop symptoms of ICD, suggesting an additional underlying neurobiological susceptibility. Furthermore, the symptoms of depression and ICD frequently coincide even though they are related to seemingly contrasting limbic CSTC circuit activation states. The aim of this review is to provide an overview of the currently available literature on the neurobiology of PD-related depression and ICD and discusses possible susceptibility factors. Finally, we propose a neurobiological model that identifies ventral striatal dopaminergic denervation as a common underlying neurobiological substrate of depression and ICD and subsequent dysfunction of reward and motivation-related brain areas.