The interplay between stress, inflammation and Parkinson's disease: insights from the COVID-19 pandemic.

Stress and inflammation are interconnected in Parkinson's disease (PD), both potentially accelerating neurodegeneration. The COVID-19 pandemic offered a unique context to study how external stress impacts inflammation in PD. We analyzed clinical and plasma data from 256 PD patients in the longitudinal Personalized Parkinson's Project, assessed both before and during the pandemic. Mixed-effects models assessed associations between stress-related symptoms and inflammatory markers, and the effects of stress reactivity (high vs. low) and time (pre- vs. during-pandemic) on inflammatory markers. Depressive symptoms were positively associated with CRP and IL-6 levels. CRP levels increased during the pandemic compared to pre-pandemic levels, especially in highly stress-reactive individuals. MMP-10 was upregulated during the pandemic, unrelated to stress or disease severity. These findings support the link between depression and low-grade inflammation in PD and suggest pandemic-related stress may exacerbate inflammatory responses. Future research may address the causal links between stress, inflammation, and PD disease progression.