Medical conditions and the risk of subsequent major depressive disorder: a nationwide, register-based, retrospective cohort study

Abstract

Background: Major depressive disorder can develop subsequent to medical conditions; however, it is unknown if some individuals are at higher risk than others. We aimed to provide comprehensive estimates for the risk of major depressive disorder subsequent to the onset of various medical conditions. Methods: In this nationwide, population-based, retrospective cohort study, individuals living in Denmark between Jan 1, 1995, and Dec 31, 2022, were included. Individuals who already had a medical condition or major depressive disorder within a 5-year washout period were excluded. Information on medical conditions and major depressive disorder was obtained from the National Danish Registries. The exposure was onset of medical conditions, defined as any of nine categories: circulatory, endocrine, pulmonary, gastrointestinal, urogenital, musculoskeletal, haematological, cancers, and neurological. The endpoint was major depressive disorder. Hazard ratios (HRs) were estimated with adjusted Cox regression models. Absolute risks were estimated with competing-risk survival analysis. Findings: 6 528 353 individuals were followed up for a total of 100 770 621 person-years. 2 114 575 (32·4%) individuals were diagnosed with a medical condition and 1 112 043 (17·0%) individuals were diagnosed with major depressive disorder. Individuals with medical conditions had a higher rate of major depressive disorder than those without (HR 2·26, 95% CI 2·25–2·28). In the first month after onset of a medical condition, the HR for major depressive disorder was 4·62 (95% CI 4·50–4·74). The HR in the first months after onset of a medical condition was further elevated in individuals aged 60 years or older (HR 9·04, 95% CI 8·63–9·47), in patients hospitalised for a medical condition (11·83, 11·25–12·45), and in those with at least two medical conditions (8·92, 8·74–9·11). Musculoskeletal conditions had the highest HR for major depressive disorder (2·50, 2·49–2·51), whereas endocrine conditions had the lowest (1·35, 1·34–1·36). More than 10 years after onset of a medical condition the HR for major depressive disorder was 1·84 (95% CI 1·82–1·86). The absolute risk for major depressive disorder 20 years after onset of a medical condition was 18·9% (18·8–19·0) in men and 24·4% (24·3–24·5) in women compared with 6·9% (6·8–7·0%) in matched men without a medical condition and 10·7% (10·6–10·8%) in matched women without a medical condition. Interpretation: Onset of medical conditions is associated with an elevated risk of major depressive disorder and is further elevated immediately after diagnosis and in specific subgroups. These findings can be used for early detection and to give attention to specific groups in the period after onset of medical conditions. Funding: The Research Council of Rigshospitalet.