For the first time, researchers have identified areas of abnormally low metabolism in the brains of adults with hyperactivity disorder, one of the leading causes of behavior and school problems, according to a study published today.
The findings, which appear in this week's issue of the New England Journal of Medicine, pinpoint key regions of the brain that apparently have altered function in people with hyperactivity, and may make possible the development of a much-needed diagnostic test for the condition, also known as attention-deficit hyperactivity disorder.
"It's very exciting," said Joseph Biederman, director of Pediatric Psychopharmacology at Massachusetts General Hospital in Boston. The report "substantiates the notion that this is a biological condition, not a purely psychological response," he said.
Hyperactivity affects 2 to 4 percent of school-age children. They show varying degrees of restlessness, inattention, distractability and impulsiveness that often lead to trouble in school and serious behavior problems.
The symptoms may persist in adulthood. Children as young as preschool age have been diagnosed with hyperactivity, although most cases are identified at about age 7. In recent years, hyperactivity also has been increasingly detected in adults in whom it went undiagnosed during childhood.
In the new study, researchers at the National Institute of Mental Health found that the rate at which the brain uses glucose, its main energy source, was 8 percent lower in a group of adults with hyperactivity than in a similar group who did not have the condition.
"Not only is brain metabolism abnormally low in this disorder, but it is low in the parts of the brain that we have known for years and years to be important for attention, handwriting, motor control and inhibiting responses," said Alan J. Zametkin, senior staff psychiatrist in NIMH's section on clinical brain imaging and principal author of the study.
Zametkin, Robert M. Cohen and their colleagues at the NIMH used a sophisticated brain-imaging technique, known as positron emission tomography (PET) scanning, to measure brain metabolism in 75 adults. They chose to study adults first because the test involves exposure to a small amount of radiation.
Included in the study were 50 healthy adults and 25 adults with hyperactivity. The hyperactive participants were all well-functioning individuals who were free of other serious medical or psychiatric conditions and who had never received medication for their hyperactivity. In addition, they all had at least one hyperactive child.
PET scans, which were developed at the NIMH by Louis Sokoloff, measure the metabolism of brain cells -- that is, the rate at which they extract energy from glucose. The study found that brain metabolism was 8 percent lower inthose with hyperactivity than in the control group. When researchers looked at specific regions in the brain, they found that 30 of 60 different regions studied had significantly lower rates of energy use in the hyperactive adults than in the control group.
The largest reductions were found in areas of the brain known as the premotor cortex and the superior prefrontal cortex -- regions that the authors note have previously been shown "to be involved in the control of attention and motor activity."
Gabrielle Weiss, professor of psychiatry at McGill University in Montreal noted in an editorial accompanying today's report that it will be important to determine whether these findings apply to "a distinct group of those with hyperactivity, or whether they apply to all with the disorder."
Researchers long believed that children with hyperactivity outgrew the condition. But studies now show that at least half of affected youngsters face lifelong problems. There is also an important genetic component to the disorder. According to studies by Harvard's Biederman, at least 30 percent of children with hyperactivity have a parent with the condition.
The PET scan results offer the hope that the procedure, or perhaps a simpler and less expensive version of the test, may prove useful to diagnose hyperactivity. At present, the diagnosis depends on observing a child's behavior and interviewing teachers and parents.
Zametkin and his colleagues are now studying adolescents and children with hyperactivity to see if their brains will show similar alterations in metabolism. They also plan to use PET scans to see what effect the commonly prescribed drug for hyperactivity has on the brain. A stimulant called methylphenidate hydrochloride, marketed under the trade name Ritalin, is the usual treatment, although its use has been controversial.
Zametkin said preliminary results suggest that stimulants may work not by boosting brain metabolism in areas with low energy use, but by better equalizing rates of energy use in the brain as a whole.