Exploring Comorbidity Within Mental Disorders among a Danish National Population

Oleguer Plana-Ripoll; Carsten Bøcker Pedersen; Yan Holtz; Michael E. Benros; Søren Dalsgaard; Peter De Jonge; Chun Chieh Fan; Louisa Degenhardt; Andrea Ganna; Aja Neergaard Greve; Jane Gunn; Kim Moesgaard Iburg; Lars Vedel Kessing; Brian K. Lee; Carmen C.W. Lim; Ole Mors; Merete Nordentoft; Anders Prior; Annelieke M. Roest; Sukanta Saha; Andrew Schork; James G. Scott; Kate M. Scott; Terry Stedman; Holger J. Sørensen; Thomas Werge; Harvey A. Whiteford; Thomas Munk Laursen; Esben Agerbo; Ronald C. Kessler; Preben Bo Mortensen; John J. McGrath

doi:10.1001/jamapsychiatry.2018.3658

Exploring Comorbidity Within Mental Disorders among a Danish National Population

Oleguer Plana-Ripoll, Carsten Bøcker Pedersen, Yan Holtz, Michael E. Benros, Søren Dalsgaard, Peter De Jonge, Chun Chieh Fan, Louisa Degenhardt, Andrea Ganna, Aja Neergaard Greve, Jane Gunn, Kim Moesgaard Iburg, Lars Vedel Kessing, Brian K. Lee, Carmen C.W. Lim, Ole Mors, Merete Nordentoft, Anders Prior, Annelieke M. Roest, Sukanta SahaAndrew Schork, James G. Scott, Kate M. Scott, Terry Stedman, Holger J. Sørensen, Thomas Werge, Harvey A. Whiteford, Thomas Munk Laursen, Esben Agerbo, Ronald C. Kessler, Preben Bo Mortensen, John J. McGrath

Department of Clinical Medicine

114 Citations (Scopus)

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 5940778 persons were included in this study (2958293 men and 2982485 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..

Original language	English
Journal	JAMA Psychiatry
Volume	76
Issue number	3
Pages (from-to)	259-270
ISSN	2168-622X
DOIs	https://doi.org/10.1001/jamapsychiatry.2018.3658
Publication status	Published - Mar 2019

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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., ... McGrath, J. J. (2019). Exploring Comorbidity Within Mental Disorders among a Danish National Population. JAMA Psychiatry, 76(3), 259-270. https://doi.org/10.1001/jamapsychiatry.2018.3658

Plana-Ripoll, O, Pedersen, CB, Holtz, Y, Benros, ME, Dalsgaard, S, De Jonge, P, Fan, CC, Degenhardt, L, Ganna, A, Greve, AN, Gunn, J, Iburg, KM, Kessing, LV, Lee, BK, Lim, CCW, Mors, O, Nordentoft, M, Prior, A, Roest, AM, Saha, S, Schork, A, Scott, JG, Scott, KM, Stedman, T, Sørensen, HJ, Werge, T, Whiteford, HA, Laursen, TM, Agerbo, E, Kessler, RC, Mortensen, PB & McGrath, JJ 2019, 'Exploring Comorbidity Within Mental Disorders among a Danish National Population', JAMA Psychiatry, vol. 76, no. 3, pp. 259-270. https://doi.org/10.1001/jamapsychiatry.2018.3658

@article{5974f63b5bfc4b83b916ec437c75762d,

title = "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 5940778 persons were included in this study (2958293 men and 2982485 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..",

author = "Oleguer Plana-Ripoll and Pedersen, {Carsten B{\o}cker} and Yan Holtz and Benros, {Michael E.} and S{\o}ren Dalsgaard and {De Jonge}, Peter and Fan, {Chun Chieh} and Louisa Degenhardt and Andrea Ganna and Greve, {Aja Neergaard} and Jane Gunn and Iburg, {Kim Moesgaard} and Kessing, {Lars Vedel} and Lee, {Brian K.} and Lim, {Carmen C.W.} and Ole Mors and Merete Nordentoft and Anders Prior and Roest, {Annelieke M.} and Sukanta Saha and Andrew Schork and Scott, {James G.} and Scott, {Kate M.} and Terry Stedman and S{\o}rensen, {Holger J.} and Thomas Werge and Whiteford, {Harvey A.} and Laursen, {Thomas Munk} and Esben Agerbo and Kessler, {Ronald C.} and Mortensen, {Preben Bo} and McGrath, {John J.}",

year = "2019",

month = mar,

doi = "10.1001/jamapsychiatry.2018.3658",

language = "English",

volume = "76",

pages = "259--270",

journal = "JAMA Psychiatry",

issn = "2168-622X",

publisher = "The JAMA Network",

number = "3",

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TY - JOUR

T1 - Exploring Comorbidity Within Mental Disorders among a Danish National Population

AU - Plana-Ripoll, Oleguer

AU - Pedersen, Carsten Bøcker

AU - Holtz, Yan

AU - Benros, Michael E.

AU - Dalsgaard, Søren

AU - De Jonge, Peter

AU - Fan, Chun Chieh

AU - Degenhardt, Louisa

AU - Ganna, Andrea

AU - Greve, Aja Neergaard

AU - Gunn, Jane

AU - Iburg, Kim Moesgaard

AU - Kessing, Lars Vedel

AU - Lee, Brian K.

AU - Lim, Carmen C.W.

AU - Mors, Ole

AU - Nordentoft, Merete

AU - Prior, Anders

AU - Roest, Annelieke M.

AU - Saha, Sukanta

AU - Schork, Andrew

AU - Scott, James G.

AU - Scott, Kate M.

AU - Stedman, Terry

AU - Sørensen, Holger J.

AU - Werge, Thomas

AU - Whiteford, Harvey A.

AU - Laursen, Thomas Munk

AU - Agerbo, Esben

AU - Kessler, Ronald C.

AU - Mortensen, Preben Bo

AU - McGrath, John J.

PY - 2019/3

Y1 - 2019/3

N2 - 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 5940778 persons were included in this study (2958293 men and 2982485 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..

AB - 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 5940778 persons were included in this study (2958293 men and 2982485 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..

U2 - 10.1001/jamapsychiatry.2018.3658

DO - 10.1001/jamapsychiatry.2018.3658

M3 - Journal article

C2 - 30649197

AN - SCOPUS:85060214766

SN - 2168-622X

VL - 76

SP - 259

EP - 270

JO - JAMA Psychiatry

JF - JAMA Psychiatry

IS - 3

ER -

Exploring Comorbidity Within Mental Disorders among a Danish National Population

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