Biomarkers of Neuropsychiatric Symptoms in Parkinson’s Disease

Parkinson’s disease (PD) is a neurodegenerative disorder primarily characterized by motor symptoms, including bradykinesia, rigidity, tremor, and postural instability. However, nonmotor symptoms, such as neuropsychiatric disturbances, significantly contribute to the disease burden and may precede motor symptom onset. Among these, anxiety, depression, and cognitive decline are common and profoundly affect patients’ quality of life. Despite their high prevalence, the mechanisms underlying neuropsychiatric symptoms in PD remain poorly understood, and the development of effective biomarkers for these conditions is an emerging area of interest. This thesis investigates the relationship between neuropsychiatric disturbances—focusing on anxiety—autonomic dysfunction, and motor symptoms in PD. By utilizing innovative physiological and behavioral measures, the research aims to uncover potential "physiomarkers" of anxiety in PD, offering insights that could improve management and enable personalized treatment strategies. The first study, "Unraveling the Relationship Between Autonomic Reactivity and Anxiety in Parkinson’s Disease," explores the link between autonomic dysfunction and anxiety using objective physiological measures such as heart rate variability and blood pressure. By comparing PD patients with and without anxiety to healthy controls, this study demonstrates how autonomic reactivity and levodopa treatment influence anxiety in PD. The second study, "Anxious Fluctuators in Parkinson's Disease: Defining the Relationship Between Motor and Anxiety Fluctuations," investigates the interaction between motor and neuropsychiatric fluctuations. Using wearable devices for continuous monitoring, this study highlights the mismatch between patient-reported and objectively measured motor symptom severity in anxious PD patients, emphasizing the need for personalized treatment approaches. The third study, "Short-Term Cardiovascular Symptom Improvement After Deep Brain Stimulation in Parkinson’s Disease: A Systematic Review," evaluates the impact of deep brain stimulation (DBS) on autonomic dysfunction. While DBS shows initial improvements in cardiovascular symptoms, these effects diminish over time, and its impact on blood pressure regulation and heart rate variability remains inconsistent, warranting further investigation. Together, these studies advance our understanding of autonomic and neuropsychiatric disturbances in PD. By identifying objective measures of nonmotor symptoms, this thesis contributes to improving diagnostic accuracy and fostering more targeted and effective management strategies for the complex manifestations of Parkinson’s disease.