Autism, ADHD Linked to Increased Mortality Risk

Heidi Splete

February 17, 2022

All-cause mortality is significantly higher for individuals with autism spectrum disorder or attention-deficit/hyperactivity disorder than for the general population, based on data from more than 600,000 individuals.

Studies of individuals with mental disorders have suggested an increased mortality risk, compared with the general population, but similar studies of individuals with autism spectrum disorder (ASD) or ADHD have yielded inconsistent results, Ferrán Catalá-López, PhD, of the Institute of Health Carlos III, Madrid, and colleagues wrote.

In a systematic review and meta-analysis published in JAMA Pediatrics, the researchers examined 27 studies including 642,260 individuals; 154,238 with ASD and 396,488 with ADHD. The studies were published up to April 1, 2021, and included deaths from natural causes (such as respiratory illness or cancer) and unnatural (external) causes, such as accident, injury, or poisoning. The proportion of females in the studies ranged from 14% to 100%; the follow-up ranged from 3 to 33 years; and three studies included first-degree relatives.

Overall, all-cause mortality was significantly higher among individuals with ASD (rate ratio, 2.37) and ADHD (RR, 2.13), compared with the general population. Among individuals with ASD, deaths from natural causes and unnatural causes were significantly increased, compared with the general population (RR, 3.80 and RR, 2.50, respectively). Among individuals with ADHD, deaths from natural causes were not significantly increased (RR, 1.62), but deaths from unnatural causes were significantly increased, compared with the general population (RR, 2.81).

Potential mechanisms to explain the excess mortality among individuals with ASD and ADHD include health determinants and biological pathways, but the complex nature of the associations make the establishment of causality a challenge, the researchers wrote in their discussion of the findings. In general, "severe mental and behavioral disorders appear to be associated with reduced life expectancy, both in terms of mortality from external causes and mortality from other medical conditions or diseases." With regard to ASD/ADHD in particular, these individuals often experience emotional and social problems as they enter adulthood. "Behaviors such as impulsivity and/or inattention can be contributing factors for injuries and unintentional incidents in children with ASD/ADHD," they added.

The study findings were limited by several factors including the possible omission of studies and the use of study-level data rather than individual participant data, as well as the limitation of electronic health records, the researchers noted. Also, the studies were mostly conducted in Western countries and the results may not be generalizable to other countries.

Although ASD and ADHD were associated with a significant increased risk of all-cause mortality, "the results should be interpreted with caution because there was evidence of heterogeneity between study estimates of the mortality risks," the researchers said. However, the results were strengthened by the large study sample, and offer a comprehensive look at the evidence supporting increased mortality risk among individuals with ASD or ADHD, and highlight the need to identify modifiable risk factors.

"Understanding the mechanisms of these associations may lead to targeted strategies to prevent avoidable deaths in high-risk groups of children and young people as an approach to improve public health," they said.

Recent Research Support Associations

The study was important because ASD and ADHD may persist into adulthood, but data from previous epidemiological studies on the impact of these disorders on mortality are inconsistent, lead author Catalá-López said in an interview.

"We conducted a systematic review and meta-analysis to evaluate all available studies of mortality associations in people with these disorders, which provide the most updated and evidence-based approach," he explained. "Our study has only become possible in the past few years because several large population-based epidemiological studies have been available reporting similar mortality-related outcomes."

Catalá-López said that the study findings have value in clinical practice. "We found that people with autism or attention-deficit/hyperactivity disorders would have an increased risk of mortality when compared to the general population. In our opinion, understanding the causes and mechanisms of these associations can lead to specific strategies to prevent avoidable deaths.

"Autism and attention-hyperactivity/deficit disorder are problems that can be managed with adequate and concrete programs at an early age, and most premature deaths, at least deaths from unnatural causes, can be prevented," Catalá-López said.

"Furthermore, we believe that these results may shed some light for future research. For example, more prospective studies would be needed, particularly to examine cause-specific mortality, in larger populations of children and youth with autism/attention-deficit/hyperactivity disorder, including some of the more common comorbidities," Catalá-López added.

Findings Support Need for Screening and Prevention Strategies

The clear message that individuals with ASD or ADHD often die of preventable or unnatural causes demands attention and "demands widespread recognition and the implementation of systematic screening and preventive approaches," Russell A. Barkley, PhD, of Virginia Commonwealth University, Richmond, and Geraldine Dawson, PhD, of Duke University, Durham, N.C., wrote in an accompanying editorial.

The studies included in the review also demonstrate that ADHD is associated with more than a twofold risk of early mortality in children and a more than a fourfold risk in mortality by age 45 years, they said.

The editorialists noted that the increased mortality risk may explain the ongoing conundrum among clinicians as to why the prevalence of ADHD seems to decline with age, "such that 5%-8% of children may meet diagnostic criteria for ADHD while that figure falls to 4%-5% of adults and 2%-3% of older adults," despite evidence that a majority of childhood cases will be rediagnosed in adulthood. However, the current study offers an alternative. "This systematic review and meta-analysis and the studies included within it make plain that another explanation is the greater loss of individuals with these conditions from the population over time owing to heightened mortality, compared with typical peers," they said.

"In addition to ADHD diagnosis, ASD diagnosis is also associated with other psychiatric comorbidities that are correlated with increased risk for mortality, including anxiety and affective disorders," the editorialists noted. Other considerations for increased mortality among individuals with ASD include different protective and risk factors associated with suicide risk, compared with the general population, as well as poorer social and daily living skills compared to the general population.

The study findings "argue for individuals with ADHD and individuals with ASD being viewed through a public health lens with screening and prevention strategies offered beginning in early childhood. These findings should also give impetus to efforts to try to reduce the first order risk factors that are predisposing to reduced life expectancy, such as obesity, substance use, poor diet, poor sleep, and limited exercise among children and adults with ASD and ADHD," they said.

"A preventive strategy would necessitate primary care physicians becoming more aware of the linkage between both ASD diagnosis and ADHD diagnosis and early mortality as well as their link to reduced [estimated life expectancy]," and such an approach could potentially reduce the higher mortality risk identified in the current review, they concluded.

Barkley reported speaking and other fees from Takeda, Medice Pharmaceutical, and AstraZeneca; book royalties from Guilford Publications and the American Psychological Association; and course royalties from ContiningEdCourses.net and Premier Educational Seminars. Dawson reported grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute of Mental Health during the submitted work and personal fees from Apple. Dawson also disclosed a patent for license to Apple, and Dawson and Duke University have benefited financially from technology and data that have been licensed to Apple. The study was supported by the Institute of Health Carlos III and Generalitat Valenciana. Researchers including lead author Catalá-López received funding from sources including the Centro de Investigación Biomédica en Red de Salud Mental; one coauthor received support from an Australian Research Council Discovery Early Career Researcher Award, a new investigator award from the Canadian Institutes of Health Research and the Drug Safety and Effectiveness Network, the Spanish Health Services Research on Chronic Patients Network, and Institute of Health Carlos III. The researchers had no financial conflicts to disclose.

This article originally appeared on MDedge.com, part of the Medscape Professional Network.

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