Summary: Study shows differential gene activity in caudate and frontal cortex in ADHD.
Researchers at the National Institutes of Health 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), a part of the NIH, found that individuals with ADHD had differences in the genes for chemicals known to be used by brain cells to communicate.
The results of the findings, published in Molecular psychiatryShow how genomic variation contributes to disease symptoms.
To date, this is the first study to examine postmortem human brain tissue for ADHD. Other approaches to studying mental health conditions include non-invasive brain scanning, which allows researchers to examine the structure and activation of areas of the brain. However, these studies lack information on how they affect gene levels and cell function and cause symptoms.
The researchers used RNA sequencing, a genomic technique known as gene expression, to examine how specific genes are turned on or off. They studied two related brain regions associated with ADHD: the caudate and the frontal cortex. These regions are known to be critical in controlling human attention. Previous research has found differences in the structure and activity of these brain regions in individuals with ADHD.
As one of the most common mental health conditions, ADHD affects about 1 in 10 children in the United States. The diagnosis usually occurs in childhood, and symptoms can persist into adulthood. Individuals with ADHD can be hyperactive and have trouble concentrating and controlling emotions, which can affect their ability to complete daily tasks and concentrate at school or work.
With technological advances, researchers have been able to identify genes associated with ADHD, but until now they have not been able to understand how the genomic differences in these genes work in the brain and contribute to the symptoms.
“Several genomic studies point to the expression of the same genes,” said Gustavo Sudre, PhD, associate investigator of the Social and Behavioral Research Branch, who led the study. “Interestingly, these gene-expression differences are similar to those seen in other conditions, such as autism, which may reflect differences in how the brain works.”
Most importantly, the researchers found that these differences affected the expression of genes that code for neurotransmitters, chemicals that brain cells use to communicate with each other. In particular, the results showed differences in gene expression for glutamate neurotransmitters, which are important for brain functions such as attention and learning.
“The study advances our understanding of ADHD by showing changes in how certain genes are expressed in the brain. This genomic variation will allow us to better understand how gene expression in the brain can contribute to ADHD symptoms,” said Philip, a senior researcher in the Social and Behavioral Sciences Branch who led the study. said Shaw, MD, Ph.D.
Postmortem studies are rare because of the limited donation of brain tissue, but they are extremely valuable because they give researchers direct experimental access to the brain.
“Such postmortem studies have accelerated our understanding of other mental health challenges, but until now, such studies have not looked at ADHD,” Dr. Shaw said.
So genetics and ADHD research news
Preliminary study: Closed access.
“Cortico-striatal transcriptome mapping in attention deficit hyperactivity disorder.” by Gustavo Sudre et al. Molecular psychiatry
Cortico-striatal transcriptome mapping in attention deficit hyperactivity disorder.
Despite the potential for identifying rare and common genetic variants for ADHD, a lack of transcriptional understanding of cortico-striatal brain circuitry has limited understanding of the molecular mechanisms of this disease.
To address this gap, we mapped the transcriptome of the caudate nucleus and anterior cingulate cortex of postmortem tissue from 60 individuals with and without ADHD. Significant gene expression was found in the anterior cingulate cortex and, to a lesser extent, in the caudate.
A significant downregulation of neurotransmitter gene pathways, particularly glutamatergic, was observed in ADHD, maintaining models of these neurotransmitters.
Consistent with the genetic overlap between mental disorders, correlations have been found between cortico-striatal transcriptomic changes in ADHD and changes seen in other neurodevelopmental and mood disorders.
This transcriptomic evidence implicates cortico-striatal neurotransmitter abnormalities in the pathogenesis of ADHD, consistent with current models of the disorder.