Disease trajectories and mortality among individuals diagnosed with depression: a community-based cohort study in UK Biobank

Abstract

Patients with depression are at increased risk for a range of comorbid diseases, with, however, unclear explanations. In this large community-based cohort study of the UK Biobank, 24,130 patients diagnosed with depression were compared to 120,366 matched individuals without such a diagnosis. Follow-up was conducted from 6 months after the index date until death or the end of 2019, for the occurrence of 470 medical conditions and 16 specific causes of death. The median age at the time of the depression diagnosis was 62.0 years, and most of the patients were female (63.63%). During a median follow-up of 4.94 years, 129 medical conditions were found to be significantly associated with a prior diagnosis of depression, based on adjusted Cox regression models. Using disease trajectory network analysis to visualize the magnitude of disease-disease associations and the temporal order of the associated medical conditions, we identified three main affected disease clusters after depression (i.e., cardiometabolic diseases, chronic inflammatory diseases, and diseases related to tobacco abuse), which were further linked to a wider range of other conditions. In addition, we also identified three depression-mortality trajectories leading to death due to cardiovascular disease, respiratory system disease and malignant neoplasm. In conclusion, an inpatient diagnosis of depression in later life is associated with three distinct network-based clusters of medical conditions, indicating alterations in the cardiometabolic system, chronic status of inflammation, and tobacco abuse as key pathways to a wide range of other conditions downstream. If replicated, these pathways may constitute promising targets for the health promotion among depression patients.

Fig. 1. Flow chart of study population selection and main analysis steps.

This figure shows the study design, the inclusion and exclusion process of study population selection, and main analysis steps.

Fig. 2. Hazard ratios (HRs) of other medical conditions among depression individuals compared to matched individuals without depression.

The X axis shows the disease categories according to ICD-10 codes A-N and S-Y. The Y axis shows the significant hazard ratios after Bonferroni correction of each medical condition when comparing depression individuals to individuals without depression. Details of the hazard ratios, number of cases, and 95% confidence intervals are listed in Supplementary Table 1.

Fig. 3. Trajectories of three main disease clusters among depression individuals.

This figure illustrates three following subgroups of disease trajectories identified in our analysis: A-Cardiometabolic diseases, B-Chronic inflammatory diseases, C-Tobacco abuse. The combined ICD-10 codes for the medical conditions are shown within the circle and round rectangle. The color of the circle represents the hazard ratios of this condition when comparing depression individuals to matched individuals without depression. The number above the arrow connecting two circles corresponds to the number of disease pairs among depression individuals. The color of the arrows indicates the odds ratio of the sequential association between the two medical conditions among depression individuals.

Fig. 4. Disease trajectories leading to mortality with different death causes among depression individuals.

This figure shows the identified disease trajectories leading to CVDD (Cardiovascular disease death), RSDD (Respiratory system disease death), and MND (Malignant neoplasm death) among depression individuals. The death causes are shown within the octagons. The combined ICD-10 codes for the medical conditions are shown within the circle and round rectangle. The color of the circle and octagon represents the hazard ratios of this medical condition when comparing depression individuals to matched individuals without depression. The number above the arrow connecting two circles and circle with octagon corresponds to the number of disease pairs among depression individuals. The color of the arrows indicates the odds ratio of the sequential association between the two medical conditions among depression individuals.