How the pattern of brain gene activity differs in individuals with ADHD

Researchers at the National Institutes of Health (NIH) have successfully identified differences
in gene activity in the brains of people with attention deficit hyperactivity disorder (ADHD).
The study, led by scientists at the National Human Genome Research Institute (NHGRI), part of the National Institutes of Health, found differences in genes that code for known chemicals that brain cells use to communicate
.
The findings, published in Molecular Psychiatry, suggest that genomic differences may contribute to symptoms
.

So far, this is the first study
to use postmortem human brain tissue to investigate ADHD.
Other ways to study mental health conditions include non-invasive brain scans, which allow researchers to examine the structure and activation
of brain regions.
However, these studies lack gene-level information and how genes affect cell function and cause symptoms
.

The researchers used a genomic technique called RNA sequencing to probe how specific genes are turned on or off, also known as gene expression
.
They studied two brain regions associated with ADHD: the caudate nucleus and the frontal cortex
.
These areas are known to play a key role in controlling a
person's attention.
Previous studies have found differences
in the structure and activity of these brain regions in people with ADHD.

As one of the most common mental health disorders, about one in ten children in the United States has ADHD
.
Diagnosis usually occurs in childhood, and symptoms may persist into adulthood
.
People with ADHD may be hyperactive and have difficulty concentrating and controlling impulses, which may affect their ability to complete daily tasks, as well as their ability to
focus at school or work.

As technology has advanced, researchers have been able to identify genes associated with ADHD, but until now they have not been able to determine how genomic differences in these genes act on symptoms in the brain
.

"Multiple types of genomic studies point to the expression of the same genes," said Dr.
Gustavo Sudre, an associate investigator in the Social and Behavioral Research Division of NHGRI's intramural research program, who led the study
.
"Interestingly, these differences in gene expression are similar to those seen in other situations, which may reflect differences in brain function, such as autism
.
"

Importantly, the researchers found that these differences affected the expression of genes encoding neurotransmitters, chemicals that brain cells use to communicate with each other
.
In particular, the findings revealed differences in gene expression of glutamate neurotransmitters, which are important
for brain functions such as attention and learning.

"This study advances our understanding
of ADHD by showing how this condition is associated with changes in the expression of certain genes in the brain.
" This brings us closer to understanding how genomic differences alter gene expression in the brain and contribute to ADHD symptoms," said
Philip Shaw, Ph.
D.
, senior investigator in the Division of Social and Behavioral Research who oversaw the study.

Autopsy studies are few due to limited brain tissue donation, but they are valuable because they provide researchers with a direct avenue
for brain experimentation.

"This kind of post-hoc research has accelerated our understanding of other mental health challenges, but to date, there have been no studies on ADHD," Dr.
Sudre said
.

Gustavo Sudre, Derek E.
Gildea, Gauri G.
Shastri, Wendy Sharp, Benjamin Jung, Qing Xu, Pavan K.
Auluck, Laura Elnitski, Andreas D.
Baxevanis, Stefano Marenco, Philip Shaw.
Mapping the cortico-striatal transcriptome in attention deficit hyperactivity disorder.
Molecular Psychiatry, 2022