How Gene Variant Linked to ADHD Could Operate

ADHD and other disorders characterized by decreased impulse control, including drug abuse, have been linked to dysfunction of the dopamine D4 receptor subtype. One subtype variant, D4.7, has been of particular interest because of its increased prevalence in those diagnosed with attention deficit-hyperactivity disorder (ADHD), but its function in ADHD has been poorly understood.

However, a mouse study published recently in Molecular Psychiatry provides insight into how D4.7 could play a role in increasing a person’s risk for ADHD and could also help explain how stimulants work to treat symptoms of ADHD.

Researchers inserted three variants of the dopamine D4 receptor into cells and into mice to investigate differences in biological activities. The researchers found that the D4.7 variant, unlike its D4.2 and D4.4 counterparts, was unable to interact with the short version of the dopamine type 2 (D2S) receptor to reduce glutamate release in a brain region associated with impulsivity and symptoms of ADHD in humans.

“Although previous studies have shown that dysfunctional dopamine D4 receptors are implicated in ADHD, this is the first study to show how this genetic difference might translate into functional deficits seen with this disorder,” Nora D. Volkow, MD, said in a press release. “Further research is needed to explore how this deficient interaction between receptors might be remedied, which could then lead to new medications for the treatment of ADHD,” added Volkow, who is director of the National Institute on Drug Abuse.

Although psychostimulant medications, which are the most commonly used treatment for ADHD, alleviate some symptoms, it is unclear how these compounds act within the brain to do so.

“Our results suggest that psychostimulants might reduce glutamate release by amplifying this D4/D2S interaction,” said Sergi Ferre, MD, the study’s primary author, said in a press release. “These results might also explain why these medications are less efficient in patients with the D4.7 variant.”

SourceScientists Show How Gene Variant Linked to ADHD Could Operate [Molecular Psychiatry]