Psychosis in Parkinson's disease: From the soft signs to the hard science

Patients with Parkinson's disease (PD) may develop a wide spectrum of non-motor symptoms during the course of illness. Psychosis is one such commonly observed non-motor symptoms of PD. Although several studies based on neuroimaging, genetics, retinal imaging, and neuropsychological evaluations have explored the pathogenesis of psychosis in PD; exact neural correlates are yet to be understood. Identification of factors related to psychosis in PD is important, as psychosis has been reported to be associated with higher rates of mortality, caregiver distress, and nursing home placements. This review highlights the potential of the previous studies to gain further insights into the soft signs and hard science related to psychosis in PD. Studies based on neuropsychological evaluations have revealed significant dysfunction in attention, executive and visuospatial functions in patients with PD and psychosis. Neuroimaging studies reveal grey matter atrophy in regions of the brain corresponding to both dorsal and ventral visual pathways, hippocampus, and cholinergic structures. Meanwhile, functional imaging studies suggest existence of an aberrant top-to-bottom visual processing system, which dominates the normal bottom-to-top system in patients with PD and visual hallucinations. Although nucleotide polymorphisms of several genes have been studied in PD patients with psychosis, those on − 45C > T polymorphisms of cholecystokinin gene (CCK) have shown the greatest promise because of its association with psychosis in PD. All these taken together, cohesively unfold the current status of research in patients with PD and psychosis. This paper also highlights the missing links and discusses the approach to future research in this field.