Stress and Parkinson's disease: from dysfunctional detection to impaired handling: a narrative review

Stress can precipitate Parkinson's disease (PD), and conversely, PD imposes substantial stress on affected individuals. Controlled studies support this bidirectional relationship. Recent observations during the Covid‑19 pandemic suggested that PD patients may sometimes display an unexpected resilience to stressful events (SE), in particular in terms of missing motor deterioration. However, this "favorable" interpretation can be misleading as PD is characterized by dysfunctional stress detection and stress processing. Furthermore, reduced stress‑related cardiac morbidity has not been demonstrated uncontestably. Indeed, detailed analyses indicate that involvement of non‑dopaminergic systems modifies-rather than mitigates-stress responses. Lewy body pathology already compromises activation of the hypothalamic-pituitary-adrenal (HPA) axis, while autonomic cardiac responses are blunted. Dysfunction of the superior colliculi impairs instant detection of stress events (SE); degeneration of the pedunculopontine nucleus disrupts appropriate motivational appraisal of the SE. Impaired contrast discrimination and olfaction hinder immediate perceptual SE assessment. Locus coeruleus involvement reduces alertness, further limiting SE evaluation. Finally, at the nexus of stress handling, dysfunctional amygdalar networks contribute to diminished autonomic reactivity and altered emotional processing. This review synthesizes current knowledge on peripheral and central stress‑related systems affected by PD pathophysiology. It outlines established, emerging, and theoretical therapeutic strategies, including approaches informed by the Stress Reduction Theory and the Attention Restoration Theory. It underscores the need for systematic investigation into stress mechanisms in PD, an area that remains insufficiently explored.