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. 2015 Jun 16;84(24):2422-9.
doi: 10.1212/WNL.0000000000001684. Epub 2015 May 20.

Depression and subsequent risk of Parkinson disease: A nationwide cohort study

Helena Gustafsson  1 , Anna Nordström  1 , Peter Nordström  2
Affiliations

Depression and subsequent risk of Parkinson disease: A nationwide cohort study

Helena Gustafsson et al. Neurology. .

Abstract

Objective: To investigate the long-term risk of Parkinson disease (PD) after depression and evaluate potential confounding by shared susceptibility to the 2 diagnoses.

Methods: The nationwide study cohort included 140,688 cases of depression, matched 1:3 using a nested case-control design to evaluate temporal aspects of study parameters (total, n = 562,631). Potential familial coaggregation of the 2 diagnoses was investigated in a subcohort of 540,811 sibling pairs. Associations were investigated using multivariable adjusted statistical models.

Results: During a median follow-up period of 6.8 (range, 0-26.0) years, 3,260 individuals in the cohort were diagnosed with PD. The multivariable adjusted odds ratio (OR) for PD was 3.2 (95% confidence interval [CI], 2.5-4.1) within the first year of depression, decreasing to 1.5 (95% CI, 1.1-2.0) after 15 to 25 years. Among participants with depression, recurrent hospitalization was an independent risk factor for PD (OR, 1.4; 95% CI, 1.1-1.9 for ≥5 vs 1 hospitalization). In family analyses, siblings' depression was not significantly associated with PD risk in index persons (OR, 1.1; 95% CI, 0.9-1.4).

Conclusions: The time-dependent effect, dose-response pattern for recurrent depression, and lack of evidence for coaggregation among siblings all indicate a direct association between depression and subsequent PD. Given that the association was significant for a follow-up period of more than 2 decades, depression may be a very early prodromal symptom of PD, or a causal risk factor.

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Figures

Figure 1
Figure 1. Flow diagram of nested case-control cohort selection
PD = Parkinson disease.
Figure 2
Figure 2. Risk of PD according to depression, from 3 months to 25 years after enrollment in the nested case-control cohort, estimated by a flexible parametric Royston–Parmar model adjusted for age, sex, education level, and comorbid diagnoses
Hazard ratios with 95% CIs are presented. CI = confidence interval; PD = Parkinson disease.
See this image and copyright information in PMC

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