Serotonin 2A Receptors and Visual Hallucinations in Parkinson Disease

Background: Complex visual hallucinations (VHs) occur in several pathologic conditions; however, the neural mechanisms underlying these symptoms remain unclear. Although dopamine may have a role, indirect evidence indicates that serotonin may also contribute to the pathogenesis of complex VHs, probably via involvement of the serotonin 2 receptor. Objective: To examine for the first time in vivo changes in serotonin 2A receptor neurotransmission among patients having Parkinson disease (PD) with VHs. Design: Case-control study. Setting: Academic research. Patients: Seven patients having PD with VHs and 7 age-matched patients having PD without VHs were recruited. Main Outcome Measures: We used the selective serotonin 2A receptor ligand setoperone F 18 during positron emission tomography among nondemented patients having PD with VHs. Results: Patients having PD with VHs demonstrate increased serotonin 2A receptor binding in the ventral visual pathway (including the bilateral inferooccipital gyrus, right fusiform gyrus, and inferotemporal cortex) as well as the bilateral dorsolateral prefrontal cortex, medial orbitofrontal cortex, and insula. Conclusions: This pilot study provides the first in vivo evidence suggesting a role for serotonin 2A receptors in mediating VHs via the ventral visual pathway in PD. Treatment studies should be performed using selective serotonin 2A receptor antagonists, which have important implications for the clinical management of VHs and psychosis in PD.