Individuals diagnosed with autism spectrum disorder (ASD) or attention-deficit/hyperactivity disorder (ADHD) in recent years carried a lower genetic burden than those diagnosed decades ago, suggesting that expanded diagnostic criteria may account for much of the increase in diagnoses.

The population-based cohort study included 17,071 individuals with ASD and 20,111 with ADHD diagnosed in Denmark from 1994 to 2016. The results showed that for every 10-year increase in diagnosis year, mean polygenic scores declined by 0.07 SDs for ASD and 0.06 SDs for ADHD. 

“In this cohort study, we found a decreasing genetic risk by year of diagnosis of ASD and ADHD over a period in which the diagnostic rate increased more than fourfold,” the investigators led by Sonja LaBianca, MD, PhD, of the University of Copenhagen in Copenhagen, Denmark.

“We interpret these results as consistent with prior studies suggesting a broadening of diagnostic criteria is the most plausible driver of increasing rates of both diagnoses,” they noted. 

The study was published online on June 10 in JAMA Psychiatry. 

Bigger Net? 

Rates of ASD and ADHD have risen sharply over recent decades, fueling debate over whether the increase reflects new risk factors, greater awareness, or changes in diagnostic practices.

The investigators examined whether the genetic risk profiles of people diagnosed with ASD or ADHD have changed as diagnosis rates increased. They analyzed data from the Danish iPSYCH cohort, including more than 17,000 individuals with ASD and more than 20,000 with ADHD diagnosed between 1994 and 2016.

The results showed that individuals diagnosed more recently had significantly lower polygenic risk scores than those diagnosed in earlier years.

The ASD polygenic risk score declined by 0.07 SDs for every 10-year increase in diagnosis year, while the ADHD polygenic score declined by 0.06 SDs per decade. Similar declines were observed for genetic liability to bipolar disorder and schizophrenia among both groups.

The genetic patterns observed most closely fit what the authors termed a “lowering threshold” scenario, suggesting that the diagnostic spectrum has expanded to include individuals with lower inherited genetic liability than those diagnosed in earlier years.

They cautioned that the study is not able to determine whether the broader diagnostic spectrum reflects improved recognition of milder presentations, evolving disease definitions, environmental influences, or a combination of these factors.

“We are limited in our ability to draw strong conclusions as to why a lowering threshold appears most consistent with our data,” they wrote.

Nonetheless, they said the findings suggest that clinical practice and diagnostic criteria have changed over time to include a broader phenotypic manifestation of ASD and ADHD, which may include individuals with less severe symptoms, different clinical presentations, or a greater contribution from environmental risk factors. 

Aligned With Clinical Practice

Reached for comment, Audrey C. Brumback, MD, PhD, assistant professor of neurology and pediatrics at the Dell Medical School at The University of Texas at Austin, and a member of the Coalition of Autism Scientists, told Medscape Medical News that the “major conclusion of the study is aligned with what we observe in clinical practice for most medical conditions, including autism and ADHD.”

“The severest cases are the ones that are characterized first. Over the years, we develop a more nuanced understanding of the condition and identify subtler versions that were always there but weren’t recognized as such,” she explained.

“I do think that having a better understanding of the common genetic variants studied in this paper and environmental factors that influence brain development is going to help us understand the subtler versions of autism that tend toward the diversity end of the autism spectrum rather than the disability end,” Brumback added. 

The study received no commercial funding. Disclosures for the authors are available with the original study publication. Brumback had no relevant disclosures.