Depression in context of low neuroticism is a risk factor for stroke A 9-year cohort study

Objective: Depression predicts stroke; however, meta-analyses show significant heterogeneity. We hypothesize that the risk of depression on incident stroke is conditional upon the relative contribution of vascular disease and of neuroticism in the underlying pathways to depression in a specific patient. We examined whether depression increases stroke in persons with low neuroticism and without preexisting cardiac disease. Methods: This was a population-based cohort study with 9-year follow-up (n = 2,050; >55 years, 52% female). The incidence of stroke was determined by self-report data as well as data from general practitioners and death certificates. Neuroticism was measured using the Dutch Personality Questionnaire and depression using the Center for Epidemiologic Studies-Depression scale. All data were analysed by Cox proportional hazards regression. Results: A total of 117 incident cases of stroke occurred during follow-up. Among persons with a history of cardiac disease (n = 401), depression predicted incident stroke independent of neuroticism level with a hazard ratio (HR) of 1.05 (95% confidence interval [CI] 1.01-1.10) (p = 0.02). In persons without cardiac disease (n = 1,649), depression and neuroticism interacted significantly in predicting incident stroke (p = 0.028). Stratified analyses showed that depression predicted incident stroke in those with low neuroticism, HR 1.05 (95% CI 1.00-1.09) (p = 0.033), but not in those with high neuroticism, HR 1.01 (95% CI 0.96-1.05) (p = 0.82). Conclusions: In persons without preexistent cardiac disease, depression is only predictive for future stroke in absence of high neuroticism. This might be explained by the hypothesis that late-life depression in context of low neuroticism is a marker of subclinical vascular disease.