Secondary depression in severe anxiety disorders: A population-based cohort study in Denmark

Background: Depression and anxiety disorders are highly comorbid conditions and a worldwide disease burden; however, large-scale studies delineating their association are scarce. In this retrospective study, we aimed to assess the effect of severe anxiety disorders on the risk and course of depression. Methods: We did a population-based cohort study with prospectively gathered data in Denmark using data from three Danish population registers: The Danish Civil Registration System, the Danish Psychiatric Central Register, and the Danish National Hospital Registry. We selected the cohort from people born in Denmark between Jan 1, 1955, and Dec 31, 2002, who we followed up from Jan 1, 1994, to Dec 31, 2012. The cohort was restricted to individuals with known parents. First, we investigated the effect of specific anxiety diagnoses on risk of single depressive episodes and recurrent depressive disorder. Second, we investigated the effect of comorbid anxiety on risk of readmission for depression, adjusting for sex, age, calendar year, parental age, place at residence at time of birth, and the interaction of age with sex. Findings: We included 3 380 059 individuals in our study cohort. The adjusted incidence rate ratio (IRR) for single depressive episodes was 3·0 (95% CI 2·8-3·1, p<0·0001) and for recurrent depressive disorder was 5·0 (4·8-5·2) in patients with severe anxiety disorders compared with the general population. Compared with control individuals, the offspring of parents with anxiety disorders were more likely to be diagnosed with single depressive episodes (1·9, 1·8-2·0) or recurrent depressive disorder (2·1, 1·9-2·2). Comorbid anxiety increased the readmission rates in both patients with single depressive episodes and patients with recurrent depressive disorder. Interpretation: Severe anxiety constitutes a significant risk factor for depression. Focusing on specific anxiety disorders might help to identify individuals at risk of depression, thereby providing new insights for prevention and treatment. Funding: The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH).