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Association of psychiatric comorbidity with the risk of premature death among children and adults with attention-deficit/hyperactivity disorder.
Open accessAbstract
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.
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“several studies13,14,15,16,17,18,19 have suggested that persons with ASD or ADHD may be associated with an increased risk of mortality; however, the results are inconsistent.”
From Mortality in Persons With Autism Spectrum Disorder or Attention-Deficit/Hyperactivity Disorder: A Systematic Review and Meta-analysis (2022) · cites this paper as [17]
In the citing paper
“several studies13,14,15,16,17,18,19 have suggested that persons with ASD or ADHD may be associated with an increased risk of mortality; however, the results are inconsistent.”
From Mortality in Persons With Autism Spectrum Disorder or Attention-Deficit/Hyperactivity Disorder: A Systematic Review and Meta-analysis (2022) · cites this paper as [17]
In the citing paper
“Our systematic review and meta-analysis of epidemiologic studies for ASD and ADHD has only become possible in the past few years because several large population-based observational studies16,17,19,21 have been published that have reported similar mortality-related outcome measures.”
From Mortality in Persons With Autism Spectrum Disorder or Attention-Deficit/Hyperactivity Disorder: A Systematic Review and Meta-analysis (2022) · cites this paper as [17]
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Metadata
- Authors
- Sun, S., Kuja-Halkola, R., Faraone, S. V., D’Onofrio, B. M., Dalsgaard, S., Chang, Z., & Larsson, H.
- Affiliations
- Karolinska Institutet (SE)
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
- SUNY Upstate Medical University (US)
- Aarhus University (DK)
- Örebro University (SE)
- Corresponding author
- Sun, Shihua
- Venue
- JAMA Psychiatry
- Publisher
- American Medical Association (AMA)
- Published
- 2019-11-01
- Volume
- 76
- Issue
- 11
- Pages
- 1141
- ISSN
- 2168-622X (ISSN-L)
- PMC
- PMC6686979
- OpenAlex
- W2966248724
- Cited by
- 155
- References
- 43
- Citations by year
- 2026: 21 · 2025: 17 · 2024: 36 · 2023: 24 · 2022: 28 · 2021: 19 · 2020: 10
- FWCI
- 11.35
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- JAMA Psychiatry (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Foundation for Suicide Prevention
- European Commission (667302)
- Lundbeckfonden (R248‐2017‐2003)
- Vetenskapsrådet
- Novo Nordisk Fonden (NNF 16OC0022018)
- National Institutes of Health
- National Institute of Mental Health (R01MH102221)
- National Institute of Environmental Health Sciences (R01ES026993)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Social Sciences › Psychology › Clinical Psychology › Child and Adolescent Psychosocial and Emotional Development
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Keywords
- attention deficit hyperactivity disorder, psychiatric comorbidity, premature mortality, cause-specific mortality, all-cause mortality, childhood ADHD, adult ADHD, comorbidity burden, cardiovascular mortality, cancer mortality, suicide, substance use disorders, psychiatric hospitalization, socioeconomic status, Sweden, register-based cohort study
- MeSH terms
- Adolescent, Adult, Attention Deficit Disorder with Hyperactivity, Mental Disorders, Child, Child, Preschool, Female, Humans, Infant, Male, Prospective Studies, Registries, Sweden, Comorbidity, Young Adult, Mortality, Premature
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