Parkinson’s disease is best known as a movement disorder, yet non-motor symptoms such as anxiety, depression and psychosis afflict over 50 percent of patients and severely impact their quality of life. Unfortunately, these non-motor symptoms are far less studied and deserve attention. The work proposed in this application will focus on one particularly debilitating feature of late-stage Parkinson’s disease, treatment-induced psychosis.
Serotonin is a chemical that transmits messages between nerve cells. Our research will examine how changes in the brain’s serotonin system lead to increased risk for treatment-induced psychosis and show that normalizing serotonin function will reduce psychosis development and expression.
In order to test our hypothesis, we will employ a common pre-clinical model of Parkinson’s disease that displays psychosis-like behavior with long-term levodopa therapy, the current “gold standard” of Parkinson’s treatment. We will then use two unique strategies to target the brain circuits that produce psychosis. The first is a genetic strategy that will selectively inhibit the serotonin brain circuit we have identified as driving treatment-related psychosis. The second is a newer, clinically available antidepressant called Vilazodone that has been shown to act on serotonin function to reduce other treatment-related complications such as levodopa-induced movement disorders, or dyskinesia.
Impact on Diagnosis/Treatment of Parkinson’s Disease:
Successful completion of this work will address a gaping hole in the Parkinson’s disease research field by identifying brain circuits through which treatment-induced psychosis occurs and validating an FDA-approved drug safe for use in humans.
Next Steps for Development:
Because Vilazodone is already approved for patients as an antidepressant, it could be rapidly repositioned for treatment of psychosis-like behavior in Parkinson’s disease patients.