Ritalin Blues

Researchers discovered that young rats given the stimulant Ritalin, the most common treatment for attention deficit hyperactivity disorder, are more likely to develop the rodent equivalent of depression. The finding raises new concerns about the widely prescribed drug and also bolsters the idea that the neurotransmitter dopamine may play an important role in both ADHD and depression in humans.

In ADHD, thought to affect between 3 and 5 percent of school-age children in the U.S., kids have trouble paying attention and cannot control their impulsive behavior. Diagnoses of the disease—and prescriptions for Ritalin—have climbed quickly in recent years. More than 2 million American children are currently diagnosed with ADHD, according to the National Institute on Drug Abuse. Yet few studies of the long-term effects of Ritalin on human children have been completed.

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In order to explore the relationship between cocaine addiction and Ritalin, William Carlezon, psychologist and director of McLean Hospital’s Behavioral Genetics Laboratory in Belmont, MA, and his colleague Susan Andersen studied how the stimulant changes the developing nervous system. They gave Ritalin to young rats for a period of time roughly equivalent to human development from age 4 to 12. As adults, these rats were much more likely to exhibit “learned helplessness,” the rodent behavior that psychologists think is much like human depression.

“No one can say for sure whether a rat is depressed,” Carlezon says. “But when we gave them a stress test, they gave up much faster than other rats.” Their lack of determination is thought to be something like the despair felt by human sufferers of depression.

The depressive rats were also less interested in cocaine than are normal lab rats, which led researchers to believe that the brain systems involving dopamine are at the root of both a tendency toward depression and an aversion to cocaine. In a young brain, they theorize, Ritalin disrupts the developing “reward” system.

“When we turn up the volume of the chemical dopamine by administering Ritalin,” Carlezon says, “the synapses that are forming disappear, and the ones still growing are cemented into place.” As a result, the rats grow up with a half-baked reward and pleasure system.

This theory points to a new direction in depression research. Previous studies have typically emphasized serotonin, the brain chemical influenced by drugs like Prozac. Carlezon now thinks that the dopaminergic system plays a larger role in depression than previously thought. “Both Ritalin and cocaine are more strongly linked to dopamine transporters than to serotonin transporters,” he explains. Inability to experience pleasure is a common symptom of depression.

Nonetheless, it’s dangerous to leap from baby rats to young humans when interpreting the results of the study, Carlezon warns. Because rats don’t develop ADHD, the experiment doesn’t necessarily shed much light on children with the disorder.

Nora Volkow, director of the National Institute on Drug Abuse, developed the theory that children with ADHD have too little dopamine in their brains. Ritalin works, she theorizes, because it “cleans up” the molecules that get rid of dopamine. In other words, it functions as a dopamine “reuptake inhibitor.”

Volkow agrees that further research of the long-term effects of Ritalin is necessary. “But we don’t want parents or doctors to panic, because that will do more damage than help,” she says. Parents of children with ADHD must weigh the risks against the consequences of not treating their child.

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