Attention-deficit/hyperactivity disorder (ADHD) is a complex disorder with a multifactorial etiology, meaning that there is no single pattern of gene activity that can fully explain its development. However, there is evidence to suggest that ADHD may be influenced by multiple genes, each with a small effect size.
The National Institutes of Health (NIH) has successfully identified differences in gene activity in people with attention deficit hyperactivity disorder’s brains (ADHD). The study, led by scientists at the National Human Genome Research Institute (NHGRI), a division of the National Institutes of Health (NIH), discovered that people with ADHD had differences in genes that code for known chemicals that brain cells use to communicate. The findings, published in Molecular Psychiatry, demonstrate how genomic differences may contribute to symptoms.
To date, this is the first study to investigate ADHD using postmortem human brain tissue. Non-invasive brain scanning allows researchers to examine the structure and activation of brain areas, which is another approach to studying mental health conditions. However, these studies lack information at the gene level about how genes may influence cell function and cause symptoms.
The study contributes to our understanding of ADHD by demonstrating how the condition is linked to changes in how certain genes are expressed in the brain. This advances our understanding of how genomic differences affect gene expression in the brain and contribute to ADHD symptoms.
Philip Shaw
The researchers used RNA sequencing, a genomic technique, to investigate how specific genes are turned on or off, also known as gene expression. They looked at two brain regions linked to ADHD: the caudate and the frontal cortex. These areas are known to be important for controlling a person’s attention. Previous research discovered differences in the structure and activity of these brain regions in ADHD patients.
ADHD is one of the most common mental health conditions, affecting approximately one in every ten children in the United States. Diagnosis is frequently made during childhood, and symptoms can last into adulthood. Individuals with ADHD may be hyperactive, have difficulty concentrating, and control impulses, which may impair their ability to complete daily tasks and focus at school or work.
Researchers have been able to identify genes associated with ADHD thanks to technological advances, but they have not been able to determine how genomic differences in these genes act in the brain to contribute to symptoms until now.
“Multiple types of genomic studies are pointing to the expression of the same genes,” said Gustavo Sudre, Ph.D., the study’s lead author and associate investigator in the Social and Behavioral Research Branch of NHGRI’s Intramural Research Program. “Intriguingly, these gene-expression differences were similar to those seen in other conditions, such as autism, which may reflect differences in how the brain functions.”
Importantly, the researchers discovered that these variations influenced the expression of genes that code for neurotransmitters, which are chemicals used by brain cells to communicate with one another. The findings revealed differences in gene expression for glutamate neurotransmitters, which are essential for brain functions like attention and learning.
“The study contributes to our understanding of ADHD by demonstrating how the condition is linked to changes in how certain genes are expressed in the brain. This advances our understanding of how genomic differences affect gene expression in the brain and contribute to ADHD symptoms” According to Philip Shaw, M.D., Ph.D., senior investigator in the Social and Behavioral Research Branch and study supervisor.
Postmortem studies are uncommon due to the scarcity of donated brain tissue, but they are extremely valuable because they allow researchers direct experimental access to the brain. “Such postmortem studies have accelerated our understanding of other mental health challenges, but until now, no such studies have looked at ADHD,” Dr. Shaw said.
