Association of Psychiatric Comorbidity With the Risk of Premature Death Among Children and Adults With Attention-Deficit/Hyperactivity Disorder - PubMed (original) (raw)
Association of Psychiatric Comorbidity With the Risk of Premature Death Among Children and Adults With Attention-Deficit/Hyperactivity Disorder
Shihua Sun et al. JAMA Psychiatry. 2019.
Abstract
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.
Conflict of interest statement
Conflict of Interest Disclosures: Dr Sun reported receiving personal fees from China Scholarship Council during the conduct of the study. Dr Faraone reported receiving grants from European Union’s Horizon 2020 Research and Innovation Programme during the conduct of the study; receiving income, potential income, travel expenses, continuing education support, and/or research support from Tris Pharma, Inc, Otsuka Pharmaceutical Co, Ltd, Arbor Pharmaceuticals, Ironshore Pharmaceuticals, Shire Pharmaceuticals, Akili Interactive Labs, VAYA Pharma, Inc, Sunovion Pharmaceuticals, Inc, Supernus Pharmaceuticals, Inc, and Genomind; and holding US patent US20130217707 A1 for the use of sodium-hydrogen exchange inhibitors in the treatment of attention-deficit/hyperactivity disorder with his institution. Dr D’Onofrio reported receiving grants from the Swedish Research Council, the American Foundation for Suicide Prevention, and the National Institutes of Health during the conduct of the study. Dr Larsson reported receiving grants from Shire Pharmaceuticals during the conduct of the study; personal fees from and serving as a speaker for Shire Pharmaceuticals and Evolan Pharma AB outside the submitted work; and sponsorship for a conference on attention-deficit/hyperactivity disorder from Shire Pharmaceuticals outside the submitted work. No other disclosures were reported.
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