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June 16, 2015; 84 (24) Article

Depression and subsequent risk of Parkinson disease

A nationwide cohort study

Helena Gustafsson, Anna Nordström, Peter Nordström
First published May 20, 2015, DOI: https://doi.org/10.1212/WNL.0000000000001684
Helena Gustafsson
From the Department of Community Medicine and Rehabilitation, Geriatrics (H.G., P.N.), and Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine (H.G., A.N.), Umeå University, Sweden.
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Anna Nordström
From the Department of Community Medicine and Rehabilitation, Geriatrics (H.G., P.N.), and Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine (H.G., A.N.), Umeå University, Sweden.
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Peter Nordström
From the Department of Community Medicine and Rehabilitation, Geriatrics (H.G., P.N.), and Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine (H.G., A.N.), Umeå University, Sweden.
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Citation
Depression and subsequent risk of Parkinson disease
A nationwide cohort study
Helena Gustafsson, Anna Nordström, Peter Nordström
Neurology Jun 2015, 84 (24) 2422-2429; DOI: 10.1212/WNL.0000000000001684

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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.

GLOSSARY

CI=
confidence interval;
ICD=
International Classification of Diseases;
NCC=
nested case-control;
NPR=
National Patient Register;
OR=
odds ratio;
PD=
Parkinson disease

Footnotes

  • Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Received November 11, 2014.
  • Accepted in final form March 9, 2015.
  • © 2015 American Academy of Neurology
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