Genetic substrates of psychosis in patients with Parkinson's disease: A critical review.

Patients with Parkinson's disease (PD) may develop several non-motor symptoms such as psychosis, depression, cognitive impairment, autonomic disturbances and sleep disturbances. Psychosis is one of the common non-motor symptoms, which commonly manifests as visual hallucinations and minor hallucinations such as sense of passage and presence. Though long-term dopaminergic therapy, longer duration of PD and cognitive impairment have been described as risk factors for emergence of psychosis in PD, predicting psychosis in PD remains challenging. Multiple studies have explored the genetic basis of psychosis in PD by studying polymorphisms of several genes. Most of the studies have focused on apolipoprotein E polymorphism followed by polymorphisms in cholecystokinin (CCK) system, dopamine receptors and transporters, HOMER gene, serotonin, catechol-o-methyltransferase, angiotensin converting enzyme and tau. Other than the studies on polymorphisms of CCK, most of the studies have reported conflicting results regarding association with psychosis in PD. Three out of four studies on CCK polymorphism have reported significant association of -45C>T polymorphism with the presence of hallucinations. The discrepancies in the results across the studies reviewed are possibly due to racial differences as well as differences in the patient characteristics. This review critically analyzes the published studies on genetic polymorphisms in patients with PD and psychosis.