Genetic Risk of Autism, ADHD Decreased as Diagnoses Increased

Among people with diagnoses of autism spectrum disorder (ASD) or attention deficit-hyperactivity disorder (ADHD), genetic risk has decreased over time, a cohort study from Denmark suggested.

Among individuals with incident diagnoses made from 1994 to 2016, a more recent ADHD diagnosis was associated with a decreased genetic risk for the disorder, as shown by difference in mean polygenic score (β estimate per 10-year increase -0.06 standard deviations, 95% CI -0.09 to -0.03, P=0.001), and other disorders, including ASD, bipolar disorder, and schizophrenia, reported Sonja LaBianca, MD, PhD, of Copenhagen University Hospital, and colleagues.

In addition, a more recent ASD diagnosis was associated with decreased genetic risk for ASD (β estimate per 10-year increase -0.07 standard deviations, 95% CI -0.10 to -0.04, P<0.001) and other disorders and traits, including bipolar disorder, schizophrenia, and educational attainment, they wrote in JAMA Psychiatry.

“This cohort study offers a new perspective for ongoing debates about increasing diagnostic rates of ASD and ADHD,” LaBianca and team concluded. “By analyzing genetic risk profiles across 2 decades of diagnoses in a large population-based case cohort, we demonstrated that individuals diagnosed more recently had systematically lower genetic risk. These findings suggest that clinical practice and diagnostic criteria have changed over time to include a broader phenotypic manifestation of ASD and ADHD.”

LaBianca told MedPage Today that “the challenge with psychiatric diseases is that there aren’t good biomarkers to allow us to determine if individuals fit into [a certain] diagnostic category.”

Polygenic risk scores are the closest thing to a biomarker, she added, reflecting the sum of genetic variants an individual has that raise the risk for developing a particular disease.

Rates of ADHD and ASD have increased in recent decades across multiple populations, LaBianca and team said. They considered three hypotheses that might be driving that trend: that clinicians might be better at diagnosing these disorders; that more individuals are being diagnosed with milder forms of disorders; or that clinicians are moving individuals from one diagnosis to another, LaBianca said.

The study’s findings were “consistent with a lowering diagnostic threshold over time,” she noted. This makes sense given revisions in both the Diagnostic and Statistical Manual of Mental Disorders-5 and the International Classification of Diseases, “where we’ve gone from these more narrowly defined childhood disorder concepts to a broader spectrum perspective,” she explained.

LaBianca stressed that her team’s findings did not support the idea of overdiagnosis. If genetic risk had decreased to the level of the control group, overdiagnosis would be a concern, but that wasn’t the case. However, if trends continued — given that their data are a decade-old — that would raise concern for overdiagnosis, she said.

Alycia Halladay, PhD, chief science officer of the Autism Science Foundation in Scarsdale, New York, told MedPage Today that the findings are “very consistent” with previous studies.

“To have yet another scientific publication confirm what has been thought of previously, that’s how you arrive at the evidence-based conclusion that the rise in autism and ADHD has been driven by changes in diagnostic practices,” she said.

The study reinforces that ASD and ADHD are “still highly genetic,” and that there is overlap between them, Halladay noted, adding that it’s not uncommon to see ASD in a family where there is ADHD and vice versa.

However, the study authors don’t “rule out” the role of environmental factors, Halladay pointed out, including location, increased awareness of disorders, an increase in services, diet, medications, and medical interventions.

LaBianca also pointed to destigmatization and increased help-seeking as other possible environmental factors.

For this study, the authors used data from the Lundbeck Foundation Initiative for Integrative Psychiatric Research study, one of the largest studies of genetic and environmental causes of mental disorders worldwide, tracking all babies born in Denmark after 1981.

The researchers mapped polygenic scores for five psychiatric outcomes (ADHD, ASD, depression, bipolar disorder, and schizophrenia) and five cognitive-behavioral outcomes (addiction, educational attainment, IQ, neuroticism, and risk-taking) to explore changes in risk profiles over time.

The study population included 17,071 individuals diagnosed with ASD (mean age at diagnosis 9.7 years, 24.6% female) and 20,111 diagnosed with ADHD (mean age at diagnosis 11 years, 29.6% female).

One limitation of the study was the lack of access to symptom-level assessments, without which the team cannot suggest that more recently diagnosed patients are “less severely affected,” LaBianca said. We can only say participants are “less genetically burdened … but you could speculate that that would be the case.”

Another limitation was that the population in Denmark is mostly white and of European descent, and in autism some “rare genetic variants” are different across cultures, Halladay said.

In the long term, LaBianca said she hopes to identify and match genetic risk profiles for certain subtypes of ADHD and ASD to the best treatments for those subtypes.

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