title: Depression and subsequent risk of Parkinson disease: A nationwide cohort study.
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.
authors.affiliation: 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.
authors.forename: Helena
authors.initials: H
authors.lastname: Gustafsson
authors.affiliation: 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.
authors.forename: Anna
authors.initials: A
authors.lastname: Nordström
authors.affiliation: 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. peter.nordstrom@germed.umu.se.
authors.forename: Peter
authors.initials: P
authors.lastname: Nordström
mesh_terms: D016022:Case-Control Studies; D015331:Cohort Studies; D003866:Depressive Disorder / Q000453:epidemiology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D010300:Parkinson Disease / Q000453:epidemiology*; D011569:Psychiatric Status Rating Scales; D012008:Recurrence; D012307:Risk Factors; D035781:Siblings; D013548:Sweden / Q000453:epidemiology; D013997:Time Factors