Psychiatric comorbidity may play an important role in the increased risk of premature death in people with attention-deficit/hyperactivity disorder (ADHD), according to a new extensive registry study conducted at Karolinska Institutet and Örebro University in Sweden. The results, which are published in JAMA Psychiatry, suggest that improved awareness and care of psychiatric comorbidities such as substance use disorders may help reduce serious outcomes associated with ADHD.

While previous research has shown that people with ADHD are at increased risk of premature death, the cause-specific risks and the potential role of psychiatric comorbidities has remained uncertain.

Studying national health registries with a sample of 2,675,615 individuals (86,670, 3.2% with ADHD diagnosis) born in Sweden between 1983 and 2009, researchers at Karolinska Institutet were able to examine cause-specific risks in ADHD, including suicide and unintentional injuries (eg, traffic accidents). The researchers also analyzed the potential role of early onset (such as autism spectrum disorders) and late-onset (such as substance use disorders) psychiatric comorbidities.

When analyzing children and adults separately, the study revealed that the risk of premature death was higher among adults with ADHD than among children. Individuals who received their ADHD diagnosis later in life also presented with a higher mortality risk compared to those who received their diagnosis earlier. Unintentional injuries and suicide were the leading causes of death among individuals with ADHD, accounting for 35.8% and 31.4% of the 414 deaths in the ADHD group, respectively.

According to the researchers, the study demonstrates in a variety of ways that psychiatric comorbidity plays an important role in the increased risk of premature death. For example, early onset psychiatric comorbidity contributed primarily to the association with death due to natural causes such as somatic diseases, whereas later-onset psychiatric comorbidity mainly influenced death due to unnatural causes, including suicide and unintentional injuries.

“Improved understanding of the role of psychiatric comorbidities for associations between ADHD and premature death could facilitate surveillance, intervention and prevention efforts,” says Shihua Sun, a doctoral student at the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, and lead author of the study.

Increased attention may help reduce serious outcomes associated with ADHD

Substance use disorders contributed substantially to the risk of death due to suicide, while the increased risk of death due to unintentional injuries seems to be present also in people with only ADHD and no psychiatric comorbidities.

“For individuals with a diagnosis of ADHD and their family members, we need to point out that most individuals with ADHD will not suffer from these serious outcomes,” says senior author Henrik Larsson, professor at Örebro University and visiting professor at Karolinska Institutet. “The take-home message is that clinicians should consider psychiatric comorbidities carefully in their risk assessments as it may assist in identifying individuals with increased risk of premature death. Increased attention and care of psychiatric comorbidities such as substance use disorders may help reduce serious outcomes associated with ADHD.”

The research was financed by Shire International GmbH, the Swedish Research Council, the Swedish Brain Foundation, the Swedish Initiative for Research on Microdata in the Social and Medical Sciences framework (Swedish Research Council), the National Institute of Mental Health, the European Union’s Horizon 2020 Research and Innovation Programme, the American Foundation for Suicide Prevention, Aarhus University Research Foundation, iPSYCH grants, the Lundbeck Foundation, the National Institutes of Health, the Novo Nordisk Foundation, and the Chinese Scholarship Council.

The work was conducted in collaboration between researchers from Karolinska Institutet, Örebro University, State University of New York (SUNY) Upstate Medical University, Indiana University and Aarhus University. Some of the authors of the study, including Henrik Larsson, have received income from pharmaceutical companies, and one of the authors (Stephen V. Faraone) holds a US patent for the use of sodium-hydrogen exchange inhibitors in the treatment of ADHD with his institution. See the scientific article for more information about potential conflicts of interest.