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Original Investigation
January 16, 2019

Exploring Comorbidity Within Mental Disorders Among a Danish National Population

Author Affiliations
  • 1National Centre for Register-based Research, Department of Economics and Business Economics, Aarhus University, Aarhus, Denmark
  • 2The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Copenhagen, Denmark
  • 3Centre for Integrated Register-based Research at Aarhus University, Aarhus, Denmark
  • 4Queensland Brain Institute, University of Queensland, St Lucia, Queensland, Australia
  • 5Mental Health Centre Copenhagen, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
  • 6Developmental Psychology, Department of Psychology, Rijksuniversiteit Groningen, Groningen, the Netherlands
  • 7Interdisciplinary Center Psychopathology and Emotion Regulation, University Medical Center Groningen, Groningen, the Netherlands
  • 8Department of Cognitive Science, University of California San Diego, La Jolla
  • 9Center for Multimodal Imaging and Genetics, School of Medicine, University of California San Diego, La Jolla
  • 10National Drug and Alcohol Research Centre, University of New South Wales, Sydney, New South Wales, Australia
  • 11Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts
  • 12Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts
  • 13Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston
  • 14Psychosis Research Unit, Aarhus University Hospital Risskov, Risskov, Denmark
  • 15Department of General Practice, Melbourne Medical School, The University of Melbourne, Parkville, Victoria, Australia
  • 16Department of Public Health, Aarhus University, Aarhus, Denmark
  • 17Copenhagen Affective Disorder Research Centre, Psychiatric Centre Copenhagen, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
  • 18Institute of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
  • 19Department of Epidemiology and Biostatistics, School of Public Health, Drexel University, Philadelphia, Pennsylvania
  • 20Queensland Centre for Mental Health Research, The Park Centre for Mental Health, Queensland, Australia
  • 21Psychosis Research Unit, Psychiatry, Aarhus University Hospital, Aarhus, Denmark
  • 22Research Unit for General Practice, Aarhus, Denmark
  • 23Institute of Biological Psychiatry, Copenhagen Mental Health Services, Copenhagen, Denmark
  • 24Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia
  • 25Metro North Mental Health, Royal Brisbane and Women’s Hospital, Brisbane, Queensland, Australia
  • 26Department of Psychological Medicine, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand
  • 27West Moreton Division of Mental Health and Specialised Services, Archerfield, Queensland, Australia
  • 28Mental Health Centre Copenhagen, Hellerup, Denmark
  • 29Faculty of Health Sciences, Copenhagen University Hospital, Copenhagen, Denmark
  • 30Institute of Biological Psychiatry, MHC Sct. Hans, Mental Health Services Copenhagen, Roskilde, Denmark
  • 31Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
  • 32School of Public Health, University of Queensland, St Lucia, Queensland, Australia
  • 33Department of Health Care Policy, Harvard Medical School, Boston, Massachusetts
JAMA Psychiatry. 2019;76(3):259-270. doi:10.1001/jamapsychiatry.2018.3658
Key Points

Question  After an individual receives a diagnosis of a specific mental disorder, does the risk of developing other mental disorders increase?

Findings  This population-based cohort study of 5 940 778 individuals, followed up for 83.9 million person-years, found that comorbidity within mental disorders was pervasive (there was an increased risk of developing all other mental disorders after an index mental disorder) and that the risk of developing comorbidity was most prominent in the first year after the onset of a mental disorder; however, the increased risk persisted over at least 15 years. For some disorders (eg, mood disorders) the absolute risks of developing specific later disorders (eg, anxiety disorders) was substantial (eg, 30%-40% over 5 years).

Meaning  If clinicians and individuals with mental disorders had ready access to diagnosis-, age-, and sex-specific absolute risks of potential future comorbidity, this information could permit more tailored interventions and better education about self-management (ie, personalized medicine).


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.