Groundbreaking study uncovers the cause of ADHD
[Dec 8, 2022: D. Halperin, Ben Gurion University]
ADHD is one of the most common neurological disorders that usually first show up during childhood. (CREDIT: Creative Commons)
Israeli scientists have cracked code to better understand the genetic causes of attention deficit hyperactivity disorder (ADHD).
This new study was carried out by researchers from the Ben-Gurion University of the Negev and Soroka-University Medical Center and was published in the peer-reviewed academic journal Nature Communications.
ADHD is one of the most common neurological disorders that usually first show up during childhood. This disorder in particular is characterized by inattention, hyperactivity, impulsivity and difficulty focusing.
But what causes it?
It is obvious that there is a genetic predisposition to it. But how exactly does it work? Which genes are affected?
According to the new study, that gene may just be CDH2, should that gene mutate.
CDH2 is a gene that encodes N-cadherin, which is responsible for helping in brain synapse activity and formation. A mutation in CDH2, however, alters this activity. This, in turn, impacts molecular pathways and dopamine levels in two specific brain structures: the ventral midbrain and the prefrontal cortex, both of which are involved in ADHD.
This was tested by using CRISPR to insert this type of mutation in homologous mouse genes, which caused hereditary hyperactivity.
The regular CDH2 gene, and the gene in mutated form as found in the Israeli family that was subject of the Ben Gurion University study, and in the mice subsequently raised. (CREDIT: Ben Gurion University)
The implications of this finding could help pave the way for further understanding how ADHD works, and how it can be treated and managed.
“We raised mice with exactly the same mutation in their genes and put them through 15 behavior tests, which show they clearly have ADHD,” one of the authors, Prof. Ohad Birk, said in a statement.
Prof. Ohad Birk (left) and his MD-PhD student Daniel Halperin (CREDIT: Ben Gurion University)
"In addition to the scientific importance of finding a clear delineation of a novel genetic basis and molecular pathways for ADHD, both the mutant human cells and the mouse strain carrying the human mutation can serve as an effective model system for the discovery of novel medications for ADHD," said Birk.
“These mice, and others like them, will become a standard tool for researchers studying ADHD, including those finding medications."
Structural analysis and disrupted cleavage of CDH2-mutated peptides. In-silico protein modeling. Ribbon representation of N-cadherin extracellular domains allows assessing the location of the identified mutation. Red, prodomain; green, extracellular cadherin domains (CADs 1-5); Blue, unstructured linker. (CREDIT: Nature Communications)
"Normally, it’s very hard to create a good animal model for studying ADHD, as several genes can be involved, and possibly also environmental factors. Here there’s just one gene that causes ADHD, and all the symptoms we look for are there, which is what makes ours such a reliable model.”
Further studies have been initiated by the Birk team at BGU’s National Institute for Biotechnology in the Negev (NIBN).
Symptoms of ADHD
Some people with ADHD have fewer symptoms as they age, but some adults continue to have major symptoms that interfere with daily functioning, according to the Mayo Clinic. In adults, the main features of ADHD may include difficulty paying attention, impulsiveness and restlessness. Symptoms can range from mild to severe.
Many adults with ADHD aren't aware they have it — they just know that everyday tasks can be a challenge. Adults with ADHD may find it difficult to focus and prioritize, leading to missed deadlines and forgotten meetings or social plans. The inability to control impulses can range from impatience waiting in line or driving in traffic to mood swings and outbursts of anger.
Adult ADHD symptoms may include:
Disorganization and problems prioritizing
Poor time management skills
Problems focusing on a task
Excessive activity or restlessness
Low frustration tolerance
Frequent mood swings
Problems following through and completing tasks
Trouble coping with stress
What's typical behavior and what's ADHD?
Further from the Mayo Clinic, almost everyone has some symptoms similar to ADHD at some point in their lives. If your difficulties are recent or occurred only occasionally in the past, you probably don't have ADHD. ADHD is diagnosed only when symptoms are severe enough to cause ongoing problems in more than one area of your life. These persistent and disruptive symptoms can be traced back to early childhood.
Diagnosis of ADHD in adults can be difficult because certain ADHD symptoms are similar to those caused by other conditions, such as anxiety or mood disorders. And many adults with ADHD also have at least one other mental health condition, such as depression or anxiety.
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Note: Materials provided above by Ben Gurion University. Content may be edited for style and length.
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