New research from investigators at the National Institutes of Health (NIH) has revealed differences in the gene activity in the brains of people identified as having attention deficit hyperactivity disorder (ADHD). The study, conducted by scientists at NIH’s National Human Genome Research Institute (NHGRI) found that people with ADHD had differences in certain genes that code for the chemicals used by brain cells to communicate.
The study, published in the journal Molecular Psychiatry, used human post mortem brain tissue, the first time this method has been used to research ADHD, which allowed the researchers to discover genes-level activities and how they might influence cell function and give rise to symptoms. The team employed RNA sequencing to probe investigate gene expression in two connected brain regions associated with ADHD—the caudate and the frontal cortex. Both regions are known to be critical in controlling a person’s attention.
“Despite advances in identifying rare and common genetic variants conferring risk for ADHD, the lack of a transcriptomic understanding of cortico-striatal brain circuitry has stymied a molecular mechanistic understanding of this disorder,” the researchers wrote.
To address this gap, the team mapped the transcriptome of the caudate nucleus and anterior cingulate cortex in post-mortem tissue from 60 people, both those with—and without—ADHD. They uncovered significant differential expression of genes in the anterior cingulate cortex and, to a lesser extent, the caudate.
“Multiple types of genomic studies are pointing towards the expression of the same genes,” said Gustavo Sudre, PhD, associate investigator in the Social and Behavioral Research Branch in NHGRI’s Intramural Research Program, who led this study. “Interestingly, these gene-expression differences were similar to those seen in other conditions, which may reflect differences in how the brain functions, such as in autism.”
Specifically, the investigators found these variations affected the gene expression to code for neurotransmitters—particularly differences in gene expression for glutamate neurotransmitters, which are known to be vital for brain functions such as attention and learning.
“The study advances our understanding of ADHD by showing how the condition is tied to changes in how certain genes are expressed in the brain,” said Philip Shaw, MD, PhD, senior investigator in the Social and Behavioral Research Branch, who supervised the study. “This allows us to inch closer to understanding how genomic differences alter gene expression in the brain and contribute to ADHD symptoms.”
The team noted that gaining access to the post-mortem brain tissue used in the study is not common due to limited donations of brain tissue. That said, these types of studies offer and opportunity to understand brain function in a way that other, non-invasive methods such as brain scans cannot provide.
“Such postmortem studies have accelerated our understanding of other mental health challenges, but to date no such studies have looked at ADHD until now,” Shaw noted.