BACKGROUND AND PURPOSE: Experimental studies support a link between stress and development of parkinsonian symptoms, but prospective population studies are lacking. The aim of the current study is to determine the effects of several psychosocial factors on the risk of Parkinson's disease (PD), as well as to identify potential pre-motor symptoms for PD in a large prospective cohort study. METHODS: In 1991-1993, a total of 9955 women and men free of PD from the Copenhagen City Heart Study were asked about major life events, economic hardship, social network, impaired sleep and vital exhaustion. The participants were followed for first-time hospitalization with PD in nationwide registers until 2011. RESULTS: Vital exhaustion was associated with a higher risk of PD hospitalization in an exposure-dependent manner (P(trend ) = 0.001), with high vs. low vital exhaustion being associated with a hazard ratio of 2.50 [95% confidence interval (CI): 1.28-4.89]. A slightly higher risk of PD hospitalization (hazard ratio = 1.49; 95% CI: 0.87-2.56) was suggested in participants with impaired sleep at baseline. No more than weak associations were observed for economic hardship, major life events or inadequate social network in the current study. CONCLUSIONS: Overall, the hypothesis that psychosocial risk factors affect the risk of PD is not supported. The results, however, suggest that vital exhaustion may be a pre-motor marker of the neurodegenerative process eventually leading to motor symptoms and clinical PD. Vital exhaustion may be useful for screening aimed at early detection and when considering disease-modifying therapies in people at high risk of clinical PD.