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Association of Psychiatric Comorbidity With the Risk of Premature Death Among Children and Adults With Attention-Deficit/Hyperactivity Disorder
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Department of Psychiatry, State University of New York (SUNY) Upstate Medical University, Syracuse, USA; Department of Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, USA.
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Psychological and Brain Sciences, Indiana University, Bloomington,USA.
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2019 (English)In: JAMA psychiatry, ISSN 2168-6238, E-ISSN 2168-622X, Vol. 76, no 11, p. 1141-1149Article in journal (Refereed) Published
Abstract [en]

Importance: A previous register-based study reported elevated all-cause mortality in attention-deficit/hyperactivity disorder (ADHD), but cause-specific risks and the potential associations of psychiatric comorbidities remain unknown.

Objectives: To investigate the all-cause and cause-specific mortality risks in ADHD and to explore the potential role of psychiatric comorbidities.

Design, Setting, and Participants: This prospective cohort study used Swedish national registers to identify 2 675 615 individuals born in Sweden from January 1, 1983, through December 31, 2009, as the study population, among whom 86 670 individuals (3.2%) received a diagnosis of ADHD during follow-up. Follow-up was completed December 31, 2013, and data were analyzed from October 2018 through March 2019.

Exposures: Attention-deficit/hyperactivity disorder identified by first clinical diagnosis or first prescription of ADHD medications as recorded in Swedish registers. Clinical diagnosis of psychiatric comorbidity was available in the National Patient Register.

Main Outcomes and Measures: All-cause and cause-specific mortalities and hazard ratios (HRs) using Cox proportional hazards regression models.

Results: In the overall cohort of 2 675 615 individuals, 1 374 790 (51.4%) were male (57 919 with an ADHD diagnosis) and 1 300 825 (48.6%) were female (28 751 with an ADHD diagnosis). Mean (SD) age at study entry was 6.4 (5.6) years. During follow-up, 424 individuals with ADHD and 6231 without ADHD died, resulting in mortality rates of 11.57 and 2.16 per 10 000 person-years, respectively. The association was stronger in adulthood (HR, 4.64; 95% CI, 4.11-5.25) compared with childhood (HR, 1.41; 95% CI, 0.97-2.04) and increased substantially with the number of psychiatric comorbidities with ADHD (HR for individuals with only ADHD, 1.41 [95% CI, 1.01-1.97]; HR for those with ≥4 comorbidities, 25.22 [95% CI, 19.60-32.46]). In adulthood, when adjusting for early-onset psychiatric comorbidity, the association between ADHD and risk of death due to natural causes was attenuated substantially and was no longer statistically significant (HR, 1.32; 95% CI, 0.94-1.85). When adjusting for later-onset psychiatric disorders, the association was attenuated to statistical nonsignificance for death due to suicide (HR, 1.13; 95% CI, 0.88-1.45) but remained statistically significant for death caused by unintentional injury (HR, 2.14; 95% CI, 1.71-2.68) or other external causes (HR, 1.75; 95% CI, 1.23-2.48).

Conclusions and Relevance: Psychiatric comorbidity appears to play an important role in all-cause and cause-specific mortality risks in ADHD. In adulthood, early-onset psychiatric comorbidity contributed primarily to the association with death due to natural causes, whereas later-onset psychiatric comorbidity mainly influenced death due to unnatural causes, including suicide and unintentional injury. These findings suggest that health care professionals should closely monitor specific psychiatric comorbidities in individuals with ADHD to identify high-risk groups for prevention efforts.

Place, publisher, year, edition, pages
American Medical Association , 2019. Vol. 76, no 11, p. 1141-1149
National Category
Psychiatry
Identifiers
URN: urn:nbn:se:oru:diva-75815DOI: 10.1001/jamapsychiatry.2019.1944ISI: 000503200800010PubMedID: 31389973Scopus ID: 2-s2.0-85070560298OAI: oai:DiVA.org:oru-75815DiVA, id: diva2:1345134
Funder
Swedish Research Council, 2018-02259The Swedish Brain Foundation, F02018-0273Novo Nordisk, 22018
Note

Funding Agencies:

Shire International GmbH

Swedish Initiative for Research on Microdata in the Social and Medical Sciences framework (Swedish Research Council) 340-2013-5867

United States Department of Health & Human Services

National Institutes of Health (NIH) - USA

NIH National Institute of Mental Health (NIMH) 1R01MH102221

European Union (EU) 667302

American Foundation for Suicide Prevention  

Aarhus University Research Foundation AUFF-E-2015-FLS-8-61

iPSYCH from the Lundbeck Foundation R102-A9118R155-2014-1724

United States Department of Health & Human Services

National Institutes of Health (NIH) - USA R01E5026993

China Scholarship Council 201600160084

Available from: 2019-08-23 Created: 2019-08-23 Last updated: 2020-01-14Bibliographically approved

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