The pattern of gene activity for ADHD has been unlocked
Summary: Study reveals differences in gene activity in caudate and frontal cortices in individuals with 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), part of the NIH, found that people diagnosed with ADHD have differences in genes that code for known chemicals that brain cells use to communicate.
The results of the findings, published in Molecular Psychiatryshow how genomic differences can contribute to symptoms.
To date, this is the first study to use postmortem human brain tissue to investigate ADHD. Other approaches to studying mental health conditions include non-invasive brain scanning, which allows researchers to examine the structure and activation of brain regions. However, these studies lack information at the gene level and how they may affect cell function and cause symptoms.
The researchers used a genomic technique called RNA sequencing to examine how specific genes are turned on or off, also known as gene expression. They studied two related brain regions associated with ADHD: the caudate and the frontal cortex. These regions are known to be critical in controlling a person’s attention. Previous research has found differences in the structure and activity of these brain regions in people with ADHD.
As one of the most common mental health conditions, ADHD affects about 1 in 10 children in the United States. The diagnosis often occurs in childhood, and symptoms may persist into adulthood. People with ADHD can be hyperactive and have difficulty concentrating and controlling impulses, which can affect their ability to complete everyday tasks and their ability to focus at school or work.
With technological advances, researchers have been able to identify genes associated with ADHD, but until now they have been unable to determine how genomic differences in those genes work in the brain to contribute to symptoms.
“Multiple types of genomic studies indicate expression of the same genes,” said Gustavo Sudre, Ph.D., research associate in the Social and Behavioral Research Branch of NHGRI’s Intramural Research Program, who led the study. “Interestingly, these differences in gene expression were similar to those observed in other conditions, which may reflect differences in the way the brain functions, such as in autism.”
Importantly, the researchers found that these differences affect the expression of genes that code for neurotransmitters, chemicals that brain cells use to communicate with each other. Specifically, the results revealed 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 how the condition is linked to changes in the way certain genes are expressed in the brain. This allows us to get closer to understanding how genomic differences alter gene expression in the brain and contribute to ADHD symptoms,” says Philip Shaw, MD, Ph.D., a senior researcher in the Social and Behavioral Research Branch, who oversaw the study.
Postmortem studies are rare because of the limited donation of brain tissue, but they are incredibly valuable because they give researchers direct experimental access to the brain.
“Postmortem studies like this have advanced our understanding of other mental health challenges, but to date no such study has looked at ADHD,” said Dr. Shaw.
About this genetics and ADHD research news
Original Research: Closed access.
“Cortico-striatal transcriptome mapping in attention deficit hyperactivity disorder” Gustavo Sudre et al. Molecular Psychiatry
Cortico-striatal transcriptome mapping in attention deficit hyperactivity disorder
Despite progress in identifying rare and common genetic variants that confer risk for ADHD, a lack of transcriptomic understanding of the cortico-striatal brain circuit has stalled the molecular mechanistic understanding of this disorder.
To address this gap, we mapped the transcriptome of the caudate nucleus and anterior cingulate cortex in postmortem tissue from 60 individuals with and without ADHD. Significant differential gene expression was found in the anterior cingulate cortex and, to a lesser extent, in the caudate.
Significant down-regulation of neurotransmitter gene pathways, especially glutamatergic pathways, appeared consistent with models implicating these neurotransmitters in ADHD.
Consistent with the genetic overlap between mental disorders, correlations were found between cortico-striatal transcriptomic changes observed in ADHD and those observed in other neurodevelopmental and mood disorders.
This transcriptomic evidence points to abnormalities of cortico-striatal neurotransmitters in the pathogenesis of ADHD, consistent with current models of the disorder.
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