Personality, stress and risk of Parkinson's disease

The objective of this thesis was to investigate the relationship of personality and stress with subsequent risk of Parkinson’s disease (PD). In Study I, we conducted a population-based cohort study using questionnaire data from the Swedish Twin Registry to explore whether the personality traits, neuroticism and introversion, were associated with later PD risk. We also explored the role of smoking as a mediator in the relationship between personality and PD. Both neuroticism and introversion were associated with an increased PD risk. Further, smoking was a significant mediator in the relationship between personality traits and PD that partly accounted for the effect of introversion, whereas it acted as a suppressor for the effect of neuroticism on PD risk.

In Study II, we wanted to further explore the main findings from study I, with the aim to examine whether the observed associations between neuroticism, smoking and PD may be causal. We conducted a two-sample Mendelian randomization study in a network framework, consisting of three main analyses: (I) causal effect of neuroticism on PD, (II) causal effect of neuroticism on smoking initiation, (III) causal effect of smoking initiation on PD. We found no support for a causal association between neuroticism and PD risk. On the other hand, the results indicated that the association between neuroticism and smoking initiation is causal and that there is a strong causal effect of smoking initiation on a reduced PD risk.

In Study III, we explored the association between occupational stress according to the job demands-control model and risk of PD. We conducted a population-based cohort study including individuals born in Sweden between 1920 and 1950 who had an occupation in 1980 or 1970. Levels of job demands and control were determined using a job-exposure matrix. High job demands was associated with increased PD risk in men, especially in men with high education, whereas high job control was associated with increased PD risk among low educated, more strongly in women. High-strain jobs (high demands and low control) were only associated with increased PD risk among men with high education, whereas active jobs (high demands and high control) were associated with increased PD risk among men with low education.

In Study IV, we conducted a population- and sibling-matched cohort study to investigate the association between stress-related disorders and neurodegenerative diseases. Stress-related disorders (i.e. post-traumatic stress disorder (PTSD), acute stress reaction, adjustment disorder, and other stress reactions) and neurodegenerative diseases (classified as primary and vascular neurodegenerative diseases, as well as Alzheimer’s disease (AD), PD, and amyotrophic lateral sclerosis (ALS)) were identified through the national patient register. We found that stress-related disorders were associated with increased risk of neurodegenerative diseases in general. The association was stronger for vascular neurodegenerative diseases, which might indicate importance of a cerebrovascular pathway. A statistically significant association was found for AD alone, but not for PD or ALS, although the estimates pointed in the same direction.

List of scientific papers

I. Sieurin J, Gustavsson P, Weibull CE, Feldman AL, Petzinger GM, Gatz M, Pedersen NL, Wirdefeldt K. Personality traits and the risk for Parkinson disease: a prospective study. Eur J Epidemiol. 2016;31(2):169-75.
https://doi.org/10.1007/s10654-015-0062-1

II. Sieurin J, Zhan Y, Pedersen NL, Wirdefeldt K. Neuroticism, smoking and the risk of Parkinson’s disease: A network Mendelian randomization study. [Manuscript]

III. Sieurin J, Andel R, Tillander A, Valdes EG, Pedersen NL, Wirdefeldt K. Occupational stress and risk for Parkinson's disease: A nationwide cohort study. Mov Disord. 2018;33(9):1456-64.
https://doi.org/10.1002/mds.27439

IV. Song H*, Sieurin J*, Wirdefeldt K, Pedersen NL, Almqvist C, Larsson H, Valdimarsdóttir UA, Fang F. Association of Stress-Related Disorders With Subsequent Neurodegenerative Diseases. JAMA Neurol. 2020;77(6):700-709. *Equal contribution.
https://doi.org/10.1001/jamaneurol.2020.0117