Molecular Imaging of the Serotonergic System in Parkinson's Disease

In the last decades, the main focus of molecular imaging of Parkinson's disease has been on non-dopaminergic systems involved in the disease alongside the pathognomonic dopaminergic changes. Molecular imaging can detect, in vivo, both presynaptic and postsynaptic serotonergic changes in the brain and has played a key role in elucidating the pathophysiology of the serotonergic system in Parkinson's disease. Alterations in the serotonergic system may happen very early in the course of the disease and have shown a leading role in the development of tremor and dyskinesias, and in several non-motor symptoms, including sleep, cognitive and neuropsychiatric disturbances. These studies increasingly recognize that the regional topography of serotonergic brain areas associates with specific dysfunctions. In parallel with this trend, more recent molecular serotonergic imaging approaches are investigating serotonergic modulatory treatment and their contributions to the improvement of cognitive functions. In this review, we discussed post-mortem, preclinical and imaging evidence of serotonergic system changes in Parkinson's disease, and described how disease-specific serotonergic changes are relevant for motor and non-motor symptoms and complications. Future directions of serotonergic imaging have been also described alongside with the novel findings on the role of serotonergic system in asymptomatic LRRK2 carriers.