New Study Discovers Genetic Differences in Black and White Children with ADHD

Researchers from the Children's Hospital of Philadelphia found there might be important genetic differences in the causes of attention-deficit hyperactivity disorder (ADHD) between patients who are Black and those who are White.

The study, which was published in the journal Scientific Reports, generated whole-genome sequences on 875 people, including 205 who were diagnosed with ADHD. The ADHD cases included 116 African-American patients and 89 patients of European ancestry.

The researchers confirmed several structural variants and target genes linked with ADHD identified in previous research, but the researchers also found 40 new structural variants in patients with ADHD. Those included a cluster of structural variants in the non-coding region of pathways involved in brain function that are very important to the development of ADHD.

But the researchers also discovered that there was just 6% of overlap in the genes impacted by single nucleotide variants (which happen when one part of a DNA sequence is altered) between ADHD patients who were of African-American descent and those who had European ancestry. Researchers hope this discovery can potentially lead to stronger targeted treatments for ADHD in the future.

Reasons for the Genetic Differences

“There are multiple neurotransmitters in the brain—mediators that brain cells/neurons use to communicate with each other—that are involved with multiple brain executive functions, such as learning, memory, attention, cognition, sleep, mood, and behavior, many of which are affected in ADHD,” senior study author Hakon Hakonarson, MD, PhD, director of the Center for Applied Genomics at the the Joseph Stokes Jr. Research Institute at the Children's Hospital of Philadelphiae, tells Verywell. Those mediators linked to ADHD include:

• Glutamate: a neurotransmitter that is critical to learning, memory, and attention
• Acetylcholine: important for cognition
• Serotonin
• Dopamine
• Adrenaline

“Mutations involving different neurotransmitter systems can lead to ADHD and, as the mutation spectrum landscape is very different in people of African American ancestry than European ancestry, some mutations are more prone to cause ADHD in people of African ancestry and other mutations of European ancestry,” Hakonarson says.

“African genomes are much more complex and have many more variants than European genomes—this is believed in part to be due to that when man moved out of Africa 20,000 to 30,000 years ago, only a small proportion of the variation moved out,” Hakonarson says. Some diseases are specific to certain genomic ancestries, he says, and that includes some genetic mutations that lead to ADHD.

How the Findings Can Impact ADHD Treatment

Typically, ADHD is treated with a combination of behavioral therapy and medication, the CDC says. For children who are preschool-aged, behavioral therapy, along with training for their parents, is typically recommended to reduce behaviors associated with ADHD as a first line of treatment before medication.

There are two main classes of medications used to treat children with ADHD, per the CDC. Those include stimulants, which are the most widely used ADHD medications, and non-stimulants, which do not work as quickly as stimulants but can have longer-lasting effects.

The genetic variants discovered in the new study impact how well patients respond to medication for ADHD, but Hakonarson is hoping to change that.

“As different mutations and different neurotransmitter mediators are affected in different people with ADHD, this opens up an opportunity for precision-based therapies to target specifically the different causes of ADHD,” Hakonarson says.

It’s unclear at this point how, exactly, this will work, but Hakonarson says his team is now focused on precision-based therapies to help address the genetic differences.

“We are likely to develop future medicines that may work better in one ethnicity/ancestry compared to another as the mutation load may be higher for that particular neurotransmitter pathway,” he says. “But the initial goal will be to fix or correct the consequences of these mutations.”

Ultimately, Hakonarson says, new medications “will likely benefit anyone that has that particular neurotransmitter pathway affected, independent of race or ethnicity.”