Summary: Study finds differences in gene activity in the caudate and frontal cortex in people with ADHD.
Researchers from 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 from the National Human Genome Research Institute (NHGRI), part of the NIH, found that people diagnosed with ADHD had differences in genes that code for chemicals known brain cells use to communicate.
The research results, published in Molecular psychiatryshow how genomic differences can contribute to symptoms.
To date, this is the first study to use post-mortem human brain tissue to study ADHD. Other approaches to studying mental health issues include noninvasive brain scanning, which allows researchers to examine the structure and activation of brain areas. However, these studies lack information at the level of genes and how they might influence 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 connected 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 revealed differences in the structure and activity of these brain regions in people with ADHD.
As one of the most common mental health problems, ADHD affects approximately 1 in 10 children in the United States. Diagnosis often occurs in childhood and symptoms may persist into adulthood. People with ADHD may be hyperactive and have difficulty concentrating and controlling their impulses, which can affect their ability to perform daily tasks and their ability to concentrate at school or work.
Thanks to advances in technology, researchers have been able to identify genes associated with ADHD, but they had 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 point to the expression of the same genes,” said Gustavo Sudre, Ph.D., research associate in the social and behavioral research arm of the NHGRI 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 brain function, such as in autism.”
Importantly, the researchers found that these differences affected the expression of genes that code for neurotransmitters, which are chemicals that brain cells use to communicate with each other. In particular, 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 how certain genes are expressed in the brain. This allows us to better understand how genomic differences alter gene expression in the brain. brain and contribute to ADHD symptoms,” says Philip Shaw, MD, Ph.D., principal investigator in the Social and Behavioral Research Branch, who supervised the study.
Post-mortem studies are rare due to the limited donation of brain tissue, but are extremely valuable because they provide researchers with direct experimental access to the brain.
“Such post-mortem studies have accelerated our understanding of other mental health conditions, but to date, no such study has focused on ADHD so far,” Dr. Shaw said.
About this genetics and ADHD research news
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“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 advances in identifying rare and common genetic variants conferring ADHD risk, the lack of transcriptomic understanding of cortico-striatal brain circuitry has hampered a molecular mechanistic understanding of this disorder.
To fill this gap, we mapped the transcriptome of the caudate nucleus and anterior cingulate cortex in postmortem tissues from 60 people with and without ADHD. Significant differential gene expression was found in the anterior cingulate cortex and, to a lesser extent, the caudate.
Significant downregulation emerged of neurotransmitter gene pathways, particularly glutamatergic, consistent with models that implicate these neurotransmitters in ADHD.
Consistent with the genetic overlap between mental disorders, correlations have been found between the 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.