RT Journal Article SR Electronic T1 Depression and subsequent risk of Parkinson disease JF Neurology JO Neurology FD Lippincott Williams & Wilkins SP 2422 OP 2429 DO 10.1212/WNL.0000000000001684 VO 84 IS 24 A1 Helena Gustafsson A1 Anna Nordström A1 Peter Nordström YR 2015 UL http://n.neurology.org/content/84/24/2422.abstract AB 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.CI=confidence interval; ICD=International Classification of Diseases; NCC=nested case-control; NPR=National Patient Register; OR=odds ratio; PD=Parkinson disease