Study points to more targeted use of Ritalin — Drug not effective for all

While examining the brains of hyperactive, inattentive boys with a new type of scanner, Harvard researchers found a reduced flow of blood into a specific area of the brain. Known as the putamen and located deep in the center of the brain, this area helps to control movement and attention.

When doctors gave the drug Ritalin to the six of 11 of these boys, blood flow into the putamen increased significantly. The same doses, however, decreased blood flow even further in five other boys.

“This study points to the putamen as an important region of the brain involved in ADHD (Attention Deficit /Hyperactivity Disorder),” says Martin Teicher, associate professor of psychiatry at Harvard Medical School. “Diminished blood flow may be a new way to objectively diagnose ADHD, rather than relying strictly on reports of behavior. The study also shows that Ritalin may not be effective for all children diagnosed with the disorder.”

Attention deficit/hyperactivity disorder ranks as one of the most common psychiatric problems among children in the United States. Estimates of how many school-age children have the disorder range from 2 million to almost 4 million, a reflection of the uncertainty of diagnosis. Most of these cases are boys 6-12 years old.

Just as the number of cases is imprecise, “so is the use of Ritalin,” Teicher concludes. “If a child behaves like we expect someone with ADHD to behave, we label the child with that disorder, then treat him or her with medication. That fails to distinguish between children who can’t sit still and those who can but don’t.”

Six of the boys in Teicher’s test fell into the first category. “Giving Ritalin to kids like these can be helpful,” he notes. “Those that benefit most from the drug have an impaired ability to control their activity. In the classroom, that can be disruptive, but on the playground they may be no more hyperactive than a normal kid.”

The finding adds to a growing body of evidence that ADHD has a biological basis; in other words, it’s not just willful, disobedient behavior. These children can be successfully treated with medication and behavior therapy, lifting a great emotional stone from the backs of harassed parents.

Teicher points out that “many girls have a more subtle but measurable form of hyperactivity that would benefit from Ritalin. Because they are not as rambunctious as boys, the disorder is underdiagnosed in girls.

“What is needed for both boys and girls are better objective tests, like blood flow measurement to the putamen, to distinguish between biological abnormalities and natural boisterousness.”

As part of the effort to avoid overmedication, this month the American Academy of Pediatrics issued new guidelines for diagnosing ADHD.

Pruning the Brain

The new brain-scanning technique used for the Ritalin studies is also employed for studies of how childhood abuse can produce lifetime changes in the brain and, hence, behavior. The technique was developed by Perry Renshaw and Luis Maas, researchers at McLean Hospital, a Harvard-affiliated teaching hospital in Belmont, Mass., where both research programs are being carried out.

At ages 5 to 7 years, an abundance of new connections among nerve cells are being made in the brain. This activity peaks at puberty, then the luxuriance of connections undergoes a natural pruning.

“It’s a normal and necessary process that fine-tunes the brain,” Teicher explains. He follows this natural cycle by examining the brains of rats, which mimic the changes in humans on a much shorter time scale.

Teicher notes that the schedule of overproduction then pruning corresponds with the waxing and waning of ADHD. “The symptoms of restlessness and inattention often decrease in adolescence, and that may be a result of the pruning of brain connections,” he says.

Girls undergo markedly less overproduction and pruning than boys. Teicher believes that is the reason why boys are much more likely to show symptoms of ADHD. “Girls are less likely to get the disorder than boys, and less likely to outgrow when they do get it,” he notes. “The reason probably involves early exposure to testosterone and other male hormones that determine the course of brain development.”

Losing connections among brain cells may work two ways. As children reach adolescence they become more vulnerable to schizophrenia, a serious disturbance in thinking, emotions, and behavior. “It well may be that pruning unmasks congenital defects not evident during the earlier years of brain overproduction,” Teicher comments.

Abuse damages brains

The malleability of young brains leads to other problems when their owners are victims of physical and sexual abuse and witnesses to violence at home and other traumas. Studies done over the past seven years on people who were mistreated before age 18 reveal alterations in brain structure that last a lifetime.

Brain scans show fewer nerve cell connections between the left and right halves of the brain. In right-handed people, the left side deals with logical thoughts and language; the right side is more involved in emotion, particularly negative emotion, and sensory perception. (The situation is more complicated in left-handers.) Fewer connections may result in a reduced ability to use thought and logic to control emotions. That, in turn, can lead to abrupt switches from rational to emotional, angry, or paranoid behavior. In extreme cases, it could provide the basis for development of multiple personalities.

Damage to other brain areas can lead to memory lapses and to feelings of déjà vu and jamais vu (familiar people and objects suddenly feel strange; for example, a person may feel unfamiliar with a place he or she has been to many times). Automatic behaviors, like continually turning the head, may occur as well as visual disturbances and hallucinations of smell.

Teicher found what he calls a “nice association” between dissociation and early verbal abuse, being yelled at repeatedly, scolded, and criticized. All the problems of integrating logical and emotional responses may occur as they do in other types of abuse. In addition, verbal abuse apparently makes people more vulnerable to other mishaps and mistreatment, such as a mugging, attack by a dog, or an automobile accident, according to Teicher.

The researchers also find unexpected differences between men and women. Males are more susceptible to neglect than females; females are more vulnerable to sexual abuse. There are also age differences. While sexual abuse affects the brain at all ages, it produces its greatest impact between 13 and 15 years. Physical abuse has its major impact before age 12.

Because they are more sensitive to neglect than girls, “boys need extra attention,” Teicher notes. “And they often get it. Rat mothers lick and groom males more than females. Human mothers hold, hug, cuddle, and rock boys more than girls.” Lack of such attention seems to effect the cerebellum, located at the lower back of the brain, an area that deals with eye movements, posture, and control of emotions and attention. That, too, apparently ties in with the overwhelming preponderance of attention deficit and hyperactivity among boys.