Skip to main content
Funded Studies

Targeting of the Raphe-Cortical Pathway to Reduce Levodopa-Induced Psychosis

Study Rationale:
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.

Study Design:
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.


  • Christopher Bishop, PhD

    Binghamton, NY United States

  • Fredric P. Manfredsson, PhD

    Phoenix, AZ United States

Discover More Grants

Search by Related Keywords

Within the Same Program

Within the Same Funding Year

We use cookies to ensure that you get the best experience. By continuing to use this website, you indicate that you have read our Terms of Service and Privacy Policy.