Genetic change in dopamine transporter linked to ADHD

Washington, July 9 : Researchers from Vanderbilt University Medical Centre have uncovered a mechanism that might be responsible for attention deficit hyperactivity disorder (ADHD) in kids

The study suggests that a genetic change in the dopamine transporter - one of the brain's dopamine-handling proteins might lead to ADHD.

While studying two brothers with ADHD, the researchers found that this altered function of the transporter gene variant supports a role for dopamine signalling in the disease.

"We believe that this is important evidence that ADHD can be caused by a functional deficit in the brain's dopamine signaling pathway," said Randy Blakely, Ph.D., director of the Center for Molecular Neuroscience.

Dopamine has roles in brain circuits linked to attention, motor function, reward and cognition, and drugs that target dopamine transporters and receptors are used to treat ADHD, bipolar disorder and schizophrenia.

The study suggests that because the altered transporter runs backward and pushes dopamine out into the space between neurons - like normal transporters do when amphetamine (and related drugs are used to treat ADHD) or 'speed,' is present, it alters dopamine signalling and contributes to the symptoms of ADHD.

While analysing, changes in this protein in patients with ADHD, they found a single "letter" change in the transporter gene.

Blakely said the particular mutation had been reported once before in a patient with bipolar disorder, which also has connections to dopamine signalling, but the functional impact of the mutation had not been pursued, Blakely said.

With the help of sensitive technology called amperometry that uses a small carbon fibre to "listen in" on how single cells release or transport dopamine, the researchers discovered that the altered transporters were running backward at an exaggerated rate, literally pushing dopamine out of the cell.

"We think this activity would short circuit the normal synaptic transmission process," Blakely said.

"Instead of the precise 'pop-pop-pop' of dopamine being released from vesicles (tiny packets of neurotransmitter), there's a cloud of dopamine bleeding out, and the dopamine signaling system is not as sharp as it should be.

"This observation unifies the action of these drugs and strongly suggests that backward-running transporters may be an important mechanism in ADHD, even for those who do not have this particular mutation," he added.

The study appears this week in The Journal of Neuroscience.

ANI