Exploring comorbidity within mental disorders among a Danish national population
Open accessAbstract
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.
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Anxiety disorders often occur alongside other conditions such as depression, substance misuse and suicidal behaviour, and place young people at increased risk of experiencing comorbidities later in life.
“They o en occur alongside other conditions such as depression, substance misuse and suicidal behaviour (Essau 2018;Hill 2011), and place young people at increased risk of experiencing comorbidities later in life (Plana-Ripoll 2019).”
From Exercise for the treatment of anxiety in children and adolescents (2022) · cites this paper as Plana-Ripoll 2019
Different facets of mental health tend to strongly covary with one another.
“different facets of mental health tend to strongly covary with one another [66]”
Comorbidity (e.g., depression, anxiety, and PTSD) may lead to increased risk of developing chronic mental disorder relative to depression or anxiety presence alone.
“Such comorbidity (e.g., depression, anxiety, and PTSD) may lead to increased risk of developing chronic mental disorder relative to depression or anxiety presence alone (42), and so this unique group needs special attention.”
From Prevalence and Psychosocial Correlates of Mental Health Outcomes Among Chinese College Students During the Coronavirus Disease (COVID-19) Pandemic (2020) · cites this paper as [42]
DSM-5 and ICD-11 refer to drug-free patients and do not adequately consider iatrogenic comorbidity.
“Current diagnostic methods in psychiatry, both DSM-5 [66] and the forthcoming ICD-11 [67], refer to patients who are drug-free and do not take the issue of iatrogenic comorbidity into adequate consideration.”
From Iatrogenic Factors in Psychopathology (2019) · cites this paper as [67]
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- Authors
- Plana-Ripoll, O., Pedersen, C. B., Holtz, Y., Benros, M. E., Dalsgaard, S., de Jonge, P., Fan, C. C., Degenhardt, L., Ganna, A., Greve, A. N., Gunn, J., Iburg, K. M., Kessing, L. V., Lee, B. K., Lim, C. C. W., Mors, O., Nordentoft, M., Prior, A., Roest, A. M., Saha, S., Schork, A., Scott, J. G., Scott, K. M., Stedman, T., Sørensen, H. J., Werge, T., Whiteford, H. A., Laursen, T. M., Agerbo, E., Kessler, R. C., Mortensen, P. B., & McGrath, J. J.
- Affiliations
- National Centre for Register-based Research, Department of Economics and Business Economics, Aarhus University, Aarhus, Denmark
- Aarhus University (DK)
- The University of Queensland (AU)
- University of Copenhagen (DK)
- Developmental Psychology, Department of Psychology, Rijksuniversiteit Groningen, Groningen, the Netherlands
- University of California San Diego (US)
- UNSW Sydney (AU)
- Broad Institute (US)
- Aarhus University Hospital (DK)
- The University of Melbourne (AU)
- Drexel University (US)
- University Medical Center Groningen (NL)
- Mental Health Services (DK)
- University of Otago (NZ)
- West Moreton Division of Mental Health and Specialised Services, Archerfield, Queensland, Australia
- Harvard University (US)
- Corresponding author
- McGrath, John J.
- ORCID
- Pedersen, Carsten Bøcker
- Holtz, Yan
- Benros, Michael E.
- Dalsgaard, Søren
- Fan, Chun Chieh
- Degenhardt, Louisa
- Ganna, Andrea
- Greve, Aja Neergaard
- Gunn, Jane
- Iburg, Kim Moesgaard
- Kessing, Lars Vedel
- Lee, Brian K.
- Lim, Carmen C. W.
- Mors, Ole
- Nordentoft, Merete
- Prior, Anders
- Roest, Annelieke M.
- Saha, Sukanta
- Schork, Andrew
- Scott, James G.
- Scott, Kate M.
- Stedman, Terry
- Sørensen, Holger J.
- Werge, Thomas
- Whiteford, Harvey A.
- Laursen, Thomas Munk
- Agerbo, Esben
- Kessler, Ronald C.
- Mortensen, Preben Bo
- McGrath, John J.
- Venue
- JAMA Psychiatry
- Publisher
- American Medical Association (AMA)
- Published
- 2019-03-01
- Volume
- 76
- Issue
- 3
- Pages
- 259
- ISSN
- 2168-622X (ISSN-L)
- PMC
- PMC6439836
- OpenAlex
- W2908945164
- Cited by
- 584
- References
- 28
- Citations by year
- 2026: 62 · 2025: 71 · 2024: 87 · 2023: 86 · 2022: 93 · 2021: 82 · 2020: 75 · 2019: 28
- FWCI
- 87.33
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- JAMA Psychiatry (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, other-oa)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- Massachusetts General Hospital
- Aarhus Universitet
- Aarhus Universitetshospital
- Drexel University
- University of Otago
- Broad Institute
- Rijksuniversiteit Groningen
- University of Melbourne
- University of Queensland
- Gentofte Hospital
- Lundbeckfonden (R208-2015-3951, R155-2014-1724, R248‐2017‐2003, R278–2018-1411)
- Rigshospitalet
- Novo Nordisk Fonden (NNF 16OC0022018, NNF18OC0031194)
- University of California, San Diego
- Stanley Center for Psychiatric Research, Broad Institute
- Metro North Hospital and Health Service
- Queensland Brain Institute
- Institute for Molecular Bioscience, University Of Queensland
- FP7 Ideas: European Research Council (294838)
- Topics
- Social Sciences › Psychology › Social Psychology › Mental Health Treatment and Access
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Mental Health Research Topics
- Health Sciences › Medicine › Epidemiology › Chronic Disease Management Strategies
- Keywords
- mental illness, psychiatric comorbidity, intellectual disability, developmental disorders, eating disorders, anxiety disorders, depression, schizophrenia, bipolar disorder, substance use disorders, competing risks survival analysis, sex differences, mental health service utilization, outpatient care, primary care visits, health care costs
- MeSH terms
- Adult, Age Factors, Mental Disorders, Denmark, Female, Humans, Male, Registries, Sex Factors, Time Factors, Cohort Studies, Comorbidity, Young Adult
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