Exploring Comorbidity Within Mental Disorders Among a Danish National Population

Abstract

Importance: Individuals with mental disorders often develop comorbidity over time. Past studies of comorbidity have often restricted analyses to a subset of disorders and few studies have provided absolute risks of later comorbidity.

Objectives: To undertake a comprehensive study of comorbidity within mental disorders, by providing temporally ordered age- and sex-specific pairwise estimates between the major groups of mental disorders, and to develop an interactive website to visualize all results and guide future research and clinical practice.

Design, setting, and participants: This population-based cohort study included all individuals born in Denmark between January 1, 1900, and December 31, 2015, and living in the country between January 1, 2000, and December 31, 2016. The analyses were conducted between June 2017 and May 2018.

Main outcomes and measures: Danish health registers were used to identify mental disorders, which were examined within the broad 10-level International Statistical Classification of Diseases and Related Health Problems, 10th Revision, subchapter groups (eg, codes F00-F09 and F10-F19). For each temporally ordered pair of disorders, overall and lagged hazard ratios and 95% CIs were calculated using Cox proportional hazards regression models. Absolute risks were estimated using competing risks survival analyses. Estimates for each sex were generated.

Results: A total of 5 940 778 persons were included in this study (2 958 293 men and 2 982 485 women; mean [SD] age at beginning of follow-up, 32.1 [25.4] years). They were followed up for 83.9 million person-years. All mental disorders were associated with an increased risk of all other mental disorders when adjusting for sex, age, and calendar time (hazard ratios ranging from 2.0 [95% CI, 1.7-2.4] for prior intellectual disabilities and later eating disorders to 48.6 [95% CI, 46.6-50.7] for prior developmental disorders and later intellectual disabilities). The hazard ratios were temporally patterned, with higher estimates during the first year after the onset of the first disorder, but with persistently elevated rates during the entire observation period. Some disorders were associated with substantial absolute risks of developing specific later disorders (eg, 30.6% [95% CI, 29.3%-32.0%] of men and 38.4% [95% CI, 37.5%-39.4%] of women with a diagnosis of mood disorders before age 20 years developed neurotic disorders within the following 5 years).

Conclusions and relevance: Comorbidity within mental disorders is pervasive, and the risk persists over time. This study provides disorder-, sex-, and age-specific relative and absolute risks of the comorbidity of mental disorders. Web-based interactive data visualization tools are provided for clinical utility.

Figure 1.. Risk of Persons With and Without a Diagnosis of a Prior Disorder Receiving a Diagnosis of Another Disorder

Each panel shows the pairwise comorbidity between prior disorders and later disorders. Some 95% CIs are obscured by the effect size symbol used to display the hazard ratio (HR). Estimates were obtained via Cox proportional hazards regression models with age as the underlying time scale, adjusting for sex and calendar time (model A) and further adjustment for other mental disorders that had onset before the prior disorder (model B). The line of unity is shown as a dotted line in each panel.

Figure 2.. Lagged Associations Between Mood Disorders and All Other Disorders

Hazard ratios (HRs) and 95% CIs are shown of receiving a diagnosis of each disorder comparing those with and without a prior diagnosis of mood disorders, and depending on time since the first diagnosis of mood disorders, and receiving a diagnosis of mood disorders comparing those with and without a prior diagnosis of each other disorder, and depending on time since the first diagnosis of the prior disorder. Estimates were obtained via Cox proportional hazards regression models with age as the underlying time scale, adjusting for sex, calendar time, and all other mental disorders that had onset before the prior disorder (model B). The reference category is persons without a diagnosis of mood disorders or persons without a diagnosis of the specific prior disorder. The line of unity is shown as a dotted line in each panel.

Figure 3.. Absolute Risks of Receiving a Diagnosis of Each Disorder After a Prior Diagnosis of Mood Disorders

A, Cumulative incidence proportions estimated across all ages of receiving a diagnosis of each later disorder after a prior diagnosis of mood disorders. B, Specific details of prior mood disorders and later neurotic disorders, stratified by age at diagnosis of mood disorders.

Figure 4.. Screenshots of Sankey Diagram and Symmetry Plot Available in the Interactive Data Visualization Website

A, Sankey diagram that shows the significant associations between all possible pairs of mental disorders. The site allows users to select male and/or female sex, or to show associations with a magnitude of effect larger than a certain threshold. B, Symmetry plot for mood disorders. On the left side, the associations in which mood disorders is the prior disorder are displayed; the bars represent the hazard ratio of receiving a diagnosis of each disorder, depending on whether persons have a previous diagnosis of mood disorders. On the right side, the associations in which mood disorders is the later disorder are displayed; the bars represent the hazard ratio of receiving a diagnosis of mood disorders, depending on whether persons have a previous diagnosis of each other disorder. The site allows users to select the main disorder of interest, male and/or female sex, linear or log scale, or different statistical models depending on potential confounders adjusted for. Dis indicates disabilities.