Working Memory, Vigilance Linked to ADHD

A study comparing cognitive endophenotypes to see which mediate genetic risk of ADHD found working memory and arousal regulation (vigilance) to be the top 2 candidates.

Joel T. Nigg, PhD

New research singles out working memory and arousal regulation as promising cognitive endophenotypes when it comes to mediating genetic risk of attention deficit hyperactivity disorder (ADHD).

The scientific literature has no shortage of studies proposing links between various traits and ADHD. Researchers from the Oregon Health and Science University (OHSU) and the State University of New York Upstate Medical University, Syracuse, wanted to take a bird’s-eye view to determine which cognitive endophenotypes mediate common variant genetic risk for ADHD.

To find out, they studied 656 children ages 7—11, assessing each child on multiple domains: working memory, arousal/alertness, response inhibition, response speed and mental clock.

“We selected 5 domains that all have substantial claims in the literature, in an effort to let them ‘compete’ head to head to see which ones best picked up the genetic signal,” Joel T. Nigg, PhD, the study’s lead author and a professor of psychiatry and behavioral neuroscience at OHSU said.

The “competition” had 2 clear winners — working memory and arousal regulation — each of which were statistically found to mediate genetic risk in the children included in the study.

Niggs said that much was predictable, but he was surprised by other findings.

“I wasn’t too surprised that working memory and arousal performed here — both have long, venerable literatures arguing they are important clues to ADHD,” Nigg said. “I was surprised that response inhibition did not show a strong finding — it has an equally strong set of claims in the literature.”

To get to those findings, the researchers undertook a complex statistical analysis. Study participants were assessed using a “multi-informant, best-estimate diagnostic procedure and laboratory measures” of traits such as working memory and processing speed.

The team then created latent variables for the cognitive measures and for teacher and parent assessments of ADHD dimensions.

Next, they created polygenic risk scores (PGS) using data from more than 55,000 individuals with and without ADHD from a database of Psychiatric Genetics Consortium.

“Cognitive measures that survived multiple testing correction for association with the PGS were evaluated for mediation with ADHD using structural equation models,” the authors wrote.

The large majority of children in the study (514) were of homogeneous European ancestry, however, the researchers noted that they found the same results for those in the European ancestry subgroup and the overall sample.

Nigg said the study helps set the stage for further research.

“The field has tended to chase each of these targets in parallel and to argue whether or not they are related to common genetic variants,” he said. “Now, based on this work, the field can do a better job of honing in on which genes are affecting the working memory and arousal aspects of ADHD, knowing that there are common variants involved.”

Nigg said researcher could also try to “look for other genetic mechanisms or other etiologies for problems in things like response inhibition.”

The study appeared last month in the Journal of the American Academy of Child and Adolescent Psychiatry. It is titled, “Working Memory and Vigilance as Multivariate Endophenotypes Related to Common Genetic Risk for Attention-Deficit/Hyperactivity Disorder.”

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