Now, researchers at McLean Hospital, the largest psychiatric teaching affiliate of Harvard Medical School, using a new brain imaging technique they developed, have identified a key area of the brain that is underactive in children with attention deficit hyperactivity disorder (ADHD).

The technique, a new form of functional magnetic resonance imaging (fMRI), also enabled the researchers to show how Ritalin restored function in ADHD children who were demonstrably hyperactive -- that is, children who had an impaired ability to sit still during a computerized motion analysis test.

The findings are significant because they provide further evidence for a biological basis for ADHD and bring new information to the discussion of Ritalin use in children and the subjectivity with which ADHD is diagnosed.

The research team, led by Martin Teicher, MD, PhD, director of McLean Hospital's Developmental Biopsychiatry Research Program, report their findings in the April 2000 issue of Nature Medicine.

The McLean study involved six healthy boys with no history of ADHD or psychiatric disorders, and 11 boys diagnosed with ADHD according to the standard DSM-IV criteria. All 17 boys also were given a computer test that uses an infrared motion analysis system to objectively measure activity, movement and attention. Six of the 11 boys who met DSM-IV criteria for ADHD were also confirmed to be hyperactive by the objective computer test.

Using their new fMRI technique, Teicher and his colleagues identified one area of the brain-the putamen-to which ADHD symptoms may be closely tied. Long-believed to be important in motor function and some aspects of attention, the putamen was shown to have diminished blood flow in the children with ADHD.

Further, the researchers found, the more objectively hyperactive or inattentive the children were, the greater was their impairment in blood flow to the putamen.

For the six ADHD boys who tested objectively hyperactive, the researchers found that use of Ritalin enhanced blood flow significantly in the putamen. Conversely, for the five ADHD boys who were not objectively hyperactive, Ritalin decreased blood flow in the putamen even further.

"This study supports other research that points to the putamen as an important region of the brain involved in ADHD, and that diminished blood flow in the putamen may be another way to objectively diagnose ADHD," said Teicher. "It also shows that Ritalin may not be effective for all children diagnosed with ADHD using only DSM-IV criteria.

"These criteria identify a mixed group of children with similar behavioral problems, some of whom have an identifiable neurobiological abnormality and a deficient capacity to sit still and pay attention. But the DSM-IV criteria are broad and seem to include children with similar behavioral problems that may arise for other reasons."

The 11 ADHD boys were treated one week at a time with randomly low, medium and high doses of Ritalin and placebo, and were scanned on each dose. The six healthy boys were not medicated and were scanned only once.

The new fMRI test, unlike conventional MRI, enabled investigators for the first time ever to study brain blood flow at rest in the boys while on Ritalin and on placebo, thus allowing them to see which area of the brain the medication was targeting and whether or not it was working.

"Many children have the capacity to sit still but do not utilize that capacity. Using our new technique, we found that children who tested objectively hyperactive had a physiological reason for not sitting still and that they are the ones who may receive the greatest benefit from Ritalin," said Teicher.

Study coauthors are Carl Anderson, PhD; Ann Polcari, RN; Carol Glod, PhD, and Perry Renshaw, MD, PhD, all of McLean Hospital; and Luis Maas, MD, of McLean Hospital and the Harvard-MIT Division of Health Sciences and Technology.

The study was funded by the National Institute of Mental Health and the National Institute for Drug Abuse.

McLean Hospital is the largest psychiatric teaching affiliate of Harvard Medical School, an affiliate of Massachusetts General Hospital and a member of Partners HealthCare System.

29-Mar-2000