Hyperactivity Study Yields Clues to Cause, Therapy : Psychiatry: Brain abnormality associated with the condition is identified. Up to 5% of children are affected.

Researchers have for the first time identified a brain abnormality associated with hyperactivity, the disorder that causes up to 5% of children to be restless, inattentive and often disruptive in the classroom.

Using a highly sensitive imaging technique to observe the activity of brain cells, psychiatrists from the National Institute of Mental Health found decreased activity in the portions of the brain that are involved in control of attention and motor functions.

Their results, reported today in the New England Journal of Medicine, “represent a clear advance in our understanding” of hyperactivity, said psychiatrist Gabrielle Weiss of Montreal Children’s Hospital in an editorial in the same journal.

“It’s exciting because it gets us much closer to more effective treatment,” said Frederick K. Goodwin, head of the federal Alcohol, Drug Abuse and Mental Health Administration.

The results will also help to explain why the stimulant Ritalin can, paradoxically, calm the children and improve their attention span. Eventually, the studies could also lead to development of better drugs for the disorder, as well as to new ways to diagnose it--a task that is often very difficult.

Hyperactivity, which is now formally called attention deficit-hyperactivity disorder, is the most common psychiatric disorder of childhood, afflicting from 2% to 5% of all youngsters. It usually begins before the child reaches school age, and affects boys about eight times as often as girls.

Some previous evidence suggests that it is at least partially genetic in origin. As many as 60% of hyperactive children continue to display the symptoms in adulthood.

“Hyperactive children are frequently in trouble with their parents and teachers and are unpopular with other children,” Weiss wrote. About 25% of them have specific learning disabilities, and another 40% exhibit a pattern of starting fights, stealing and lying, or of disobedience, defiance and rule breaking.

Between 70% and 80% have their symptoms alleviated by taking the stimulant Ritalin, which is the most common form of therapy. As many as 800,000 Americans are now taking the drug for the disorder.

Psychiatrist Alan J. Zametkin and his colleagues at the National Institute of Mental Health studied 25 adults who were mildly hyperactive and 50 normal adults using a technique called positron emission tomography. The researchers injected sugar molecules labeled with a radioactive isotope into the subject’s bloodstream and used the scanning technique to monitor how brain cells use the sugar.

Zametkin and his colleagues found that the brains of the hyperactive adults used, on average, 8.1% less sugar than those of the normal controls, indicating that the brain cells were 8.1% less active. The largest reductions in activity were found in regions called the pre-motor cortex and the superior prefrontal cortex--regions that have been shown to be involved in the control of attention and motor activity.

“I’m very enthusiastic because . . . this gives us a window into the brain to know what areas are involved,” said psychiatrist James Satterfield of the National Center for Hyperactive Children in Encino. “It’s an exciting time because we’ve never been able to do this kind of thing before.”

Zametkin cautioned that his studies involved a very select group of patients: adults with mild hyperactivity who have never taken Ritalin and who have a hyperactive child themselves. Adults were chosen for the five-year study because the researchers did not want to infuse a radioactively labeled compound into children, because of the potential health risk and the children’s inability to give free consent to the procedure.

They are now studying teen-agers with no family history of hyperactivity in order to determine if the results can be extended to all types of patients. Zametkin said the studies are easier now that the researchers know precisely where to look for evidence of reduced activity. “And by studying younger and sicker kids, we may find a greater reduction (of activity),” he said.

He said they may eventually--and “very carefully”--extend the studies to still younger children in hopes that the technique might provide a definitive way to diagnosis the disorder.

The mental health institute group has also studied the effects of Ritalin on the patients in the hope of understanding how the drug works, but they are not yet ready to reveal their results because they have not been published.

Zametkin noted that previous studies in animals have shown that Ritalin increases the activity of brain cells, but added that “I would never in a million years bet a nickel that it is going to do the same thing in humans.”

The discovery would seem to close the door on the already discredited hypotheses that hyperactivity is caused by food additives or excessive sugar consumption.