Attention Deficit: Is It In The Genes?

New research suggests it is. Now a reliable test and more treatment options are in sight

Many parents have long suspected that their lively kids are being diagnosed, too quickly, as victims of attention deficit hyperactivity disorder. A new study suggests they're right. At Michigan State University, researchers reviewed 15 months' worth of Medicaid billing records and found that 233 children between the ages of one and three were diagnosed with ADHD--an alarming age to be judged for a disorder that can be hard to diagnose even in school-age kids. Even more troubling, nearly 60% of those toddlers were treated with psychotropic medications such as Ritalin and Prozac, though little is known about the impact of such drugs on children so young. "I don't think we can give a simple diagnosis of ADHD in a child of this age," warns Dr. Marsha D. Rappley, associate professor of pediatrics at Michigan State.

That may change in the next few years. Right now there is no objective diagnostic test for ADHD that can point to a biological malfunction, though some 3 million children and 4 million adults in the U.S. are thought to suffer from it. ADHD is characterized by a persistent pattern of impulsive behavior, inability to pay attention, and hyperactivity. The most common treatment is Novartis' Ritalin, a mild stimulant that helps the brain disregard distracting stimuli.

Over the years, doctors have blamed the condition on a dysfunctional home environment, brain damage at birth, even refined sugar and food additives. All these theories have been disproved. But highly sophisticated brain-scanning technology seems to have finally honed in on the biological cause. Researchers now blame a genetically induced imbalance of the brain chemical dopamine.

Dopamine modulates the activity of neurons associated with emotions and movement. People who carry the gene associated with ADHD apparently overproduce dopamine, which impairs their self-control and inhibitions. Based on this discovery, a diagnostic test is now in clinical trials that may be able to finally determine exactly who does and does not have the disorder.

Boston Life Sciences Inc., a small biotech startup in Boston, has developed an agent, Altropane, that binds to the brain cells that create dopamine. When used with a relatively simple brain-scanning method called single photon emission computer tomography (SPECT), doctors can determine if patients have the elevated number of dopamine-producing neurons associated with ADHD. Altropane is already in the final stage of clinical trials as a diagnostic agent with Parkinson's disease, caused when the brain cells that produce dopamine die off.

PREVALENT DISORDER. Dr. Alan J. Fisch- man, director of nuclear medicine at Massachusetts General Hospital, says preliminary studies of adult patients with longstanding ADHD found that all had a much higher level of dopamine-producing neurons than non-ADHD adults of the same age. He cautions that the test must be still be tried on a far larger population, but early results hold out promise for a method that would allow both a quick, accurate diagnosis and a treatment individually tailored to the patient's dopamine imbalance.

An accurate ADHD test would likely be in huge demand. Various studies have estimated that between 3% and 9.5% of all school-age children worldwide have the disorder, and half of these children manifest symptoms throughout their lives. But despite its prevalence, ADHD is one of the most controversial childhood disorders. A panel of experts convened a year ago by the National Institutes of Health to settle on treatment standards for ADHD concluded that it had too little information to form a consensus. "There is no consistency in treatment, diagnosis, or follow-up for children with ADHD," lamented panel chair Dr. David J. Kupfer, professor of psychiatry at the University of Pittsburgh School of Medicine. "It is a major public health problem."

The situation creates an paradox. "I think what's going on is that ADHD is overdiagnosed and undertreated," says Dr. Joseph Biederman, director of the pediatric psychopharmacology unit at Mass General. Because many of the symptoms of ADHD are similar to other psychological problems, doctors not trained to recognize the disorder may slap the ADHD label on any hard-to-handle kid. This is particularly true for boys, who are diagnosed with ADHD five to nine times as often as girls. Dr. Mark A. Stein, director of the ADHD program at Children's National Medical Center in Washington, D.C., says about 40% of the children referred to him have been misdiagnosed by doctors who did not bother to test for such problems as sleep disorders, depression, even mild retardation. "We waste so much money by not trying to figure out exactly what their problem is," says Stein.

ADDICTION FEARS. Even if a good test is devised, there still needs to be a consensus on treatment. Less than half of all kids diagnosed with ADHD take Ritalin, despite its proven effectiveness and limited side effects. Parents often resist Ritalin therapy because they don't like their children taking pills throughout the day, and they fear addiction. However, a recent four-year study by Biederman of boys diagnosed with ADHD found that those treated with Ritalin or similar stimulants were three times less likely as untreated boys to develop later substance abuse problems.

Some newer ADHD drugs in development could be more popular with parents, says Piper Jaffray Inc. analyst Peter L. Ginsburg. Celgene Corp.'s Attenade and Alza Corp.'s Concerta are both longer-acting versions of the same stimulant used in Ritalin, so do not need to be taken as often. Shire Richwood Inc.'s Adderall, an amphetamine, has also proven effective against ADHD. Ginsburg estimates that these drugs should broaden demand, boosting sales of ADHD treatment in the U.S. from $300 million a year now to between $800 million and $1 billion by 2003. And with a new diagnostic test, parents and doctors alike could be more confident that the right kids are getting the proper therapy.

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