Stress-resilience in Parkinson's disease: predictors and associations with symptom progression

Abstract Background: People with Parkinson’s disease (PD) are very sensitive to psychological stress, but not everybody reacts the same to adversity. The ability to maintain mental health despite adverse events has been conceptualized as stress-resilience. It is unclear whether stress-resilience in PD is predominantly determined by dopamine deficiency, psychosocial factors, or both. In animal models of PD, chronic stressors accelerate disease progression, but evidence in humans is lacking. Objectives: (1) Distinguish stress-reactive from stress-resilient PD patients, (2) identify predictors for stress-resilience (resilience factors), and (3) compare symptom progression between stress-reactive and resilient patients. Methods: We conducted a longitudinal survey in Personalized Parkinson Project participants ( N =350 PD). The COVID-19 pandemic was used as a model of a stressor that was aligned in time for the entire cohort. COVID-19-related stressors, perceived stress, and severity of PD symptoms were assessed at 11 timepoints (April-October 2020). In 322 patients, both pre-COVID and in-COVID objective clinical assessments were available. We quantified individual stressor-reactivity as the residual between actual and predicted perceived stress relative to COVID-19-related stressors, and modeled trajectories of stressor-reactivity across timepoints. We explored pre-COVID predictors of 6-month average stressor-reactivity and tested whether high/low average stressor-reactivity was prospectively associated with one-year clinical progression rates. Results: Latent class trajectory models distinguished patients with high ( N =227) or low ( N =123) stressor-reactivity. Pre-existing anxiety, rumination and non-motor symptom severity predicted high stressor-reactivity (risk factors), whereas quality of life, social support, positive appraisal style and cognitive abilities predicted low stressor-reactivity (resilience factors). PD-specific factors, such as disease duration, motor symptom severity and levodopa use, did not predict stressor-reactivity. During the pandemic, motor symptom progression was not accelerated, but depressive symptoms increased specifically in stress-reactive patients. Conclusion: High stressor-reactivity in PD relates to non-motor symptoms and psychosocial factors, rather than to PD-specific factors. Stressor-reactivity is associated with larger increases in depression but not motor symptoms during follow-up.