McLean Researchers Uncover New Link Between Ritalin and Brain

Discovery Could Lead to New Methods for Diagnosing and Treating ADHD

July 31, 2002

Public Affairs

Belmont, MA - McLean Hospital researchers have made a discovery that could help clinicians identify those children with attention deficit hyperactivity disorder (ADHD) who will most benefit from Ritalin. The discovery, reported in the August American Journal of Psychiatry, could also lead to new methods for diagnosing this often confusing disorder.

The researchers, led by Carl M. Anderson, PhD, and Martin Teicher, MD, PhD, of the Brain Imaging Center and Developmental Biopsychiatry Research Program at McLean Hospital, monitored the effects of Ritalin on two forms of activity-overall movement and neural activity in an obscure area of the brain, the vermis-in 10 boys with ADHD. Those who displayed high levels of both forms of activity at the start of the study were most likely to benefit from Ritalin. They displayed less kinetic movement and neural activity levels in their vermis appeared to drop after receiving the drug. Those with low initial levels of the two forms of activity exhibited little change or a slight increase in vermis activity.

Whether the apparently high levels of neural activity in the vermis of the most active boys contribute to their overall hyperactivity is not clear, due in large part to lack of attention. ADHD researchers are just beginning to recognize the role of the vermis, which is located in the cerebellum. "The vermis is a completely new frontier in ADHD research," said Anderson.

Though preliminary, the current findings could help address a longstanding debate about the appropriate use of Ritalin and also the correct diagnosis of ADHD in American children. The techniques used in the study to precisely measure not just vermis activity but also overall movement, or hyperactivity, could lead to more refined methods of prescribing medications and of making diagnoses of ADHD, Anderson said.

"ADHD is a very heterogeneous disorder. If we have some way to start categorizing patients that is connected to the underlying neurobiology, that is going to be beneficial. That is the great value of this study."

Until recently, most ADHD researchers tended to focus on two other areas of the brain—the frontal lobe and the basal ganglia, a cluster of nuclei deep in the brain. But there were hints that the vermis might play a role. For example, a massive study by National Institutes of Health researchers showed that it tends to be smaller in children with ADHD.

In the current study, Anderson and his colleagues measured the overall movement patterns of 10 boys, as well as their vermis neural activity levels, to see if there was a more substantive link. Each had been diagnosed with ADHD, the symptoms of which include hyperactivity, inattention or both. The children were put on a series of four week-long doses of Ritalin-0, 0.5, 0.8, and 1.5mg/kg. At the end of each week, a series of measurements were taken on each child, including behavioral evaluations by parents and teachers and, in Teicher's lab, a movement assessment and a functional brain image.

Key to the success of the project were two new techniques developed or refined by McLean researchers. The first is a new instrument developed in Teicher's lab that uses an optical tracking camera against an infrared background to measure tiny changes in children’s movement. The second is T2 relaxometry, which was refined in the lab of Perry Renshaw, MD, PhD, director of the Brain Imaging Center at McLean. It is a method for imaging and quantifying blood flow, a measure of neural activity, in specific areas of the brain.

The discovery that only those children with initially high levels of hyperactivity and vermis neural activity benefit from Ritalin addresses a controversy in the ADHD community. Although stimulants are known to have a rate-dependent effect-alleviating symptoms in severely affected patients, increasing activity in those less affected and normal subjects-many researchers and clinicians did not think Ritalin's effect on ADHD fell into this category. "This study shows rate-dependence is very strong for the vermis," Anderson said.

He believes that the information could be used to enhance Ritalin's effect, and possibly to design new drugs for ADHD. "Up until now, the whole mindset has been the frontal lobes," Anderson said. "This study suggest that when people are designing new drugs they might be more interested in targeting the cerebellum."

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