Identifying and targeting the neural basis of depression in Parkinson's disease

Depression is a common and debilitating complication in Parkinson’s disease (PD), affecting up to half of all individuals with PD and significantly worsening their quality of life. Despite its prevalence, depression in Parkinson’s disease (dPD) remains poorly understood, and current antidepressant therapies are often ineffective. This knowledge gap highlights the urgent need to uncover the distinct neural mechanisms underlying dPD and to explore new therapeutic strategies that can address its unique features. This project seeks to pinpoint the specific synaptic and brain network changes that differentiate dPD from PD without depression, major depressive disorder (MDD), and healthy individuals, using advanced imaging methods such as PET and fMRI. In addition, the study will assess whether ketamine, a rapid-acting antidepressant, can reverse synaptic deficits and alleviate depressive symptoms in dPD. By clarifying the biological basis of dPD and testing a promising intervention, this research could inform the development of targeted treatments and improve outcomes for people with Parkinson’s disease.