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Immune System Gene Tied to ADHD

Study marks first time body's protection system linked to disorder

MONDAY, Jan. 7, 2002 (HealthDayNews) -- Scientists hunting for genetic links to attention deficit-hyperactivity disorder (ADHD) say they've found a novel lead: A variation in an immune system gene may be tied to the behavior problem.

The discovery by Israeli researchers centers on molecules that block a substance called interleukin-1 (IL-1), a key actor in the adult brain. It protects neurons as they age, and guards against various non-immune stresses. The protein also appears to be involved in setting up the development of neurons early in life, encouraging the healthy growth of brain cells that secrete and respond to dopamine -- a vital brain chemical implicated in ADHD.

Earlier studies have pointed to other genes that regulate brain activity in ADHD, which affects between 3 percent and 5 percent of American schoolchildren. However, the latest study, which appears in the January issue of Molecular Psychiatry, is the first to suggest that the immune system may play a role.

Russell Barkley, an ADHD expert at the University of Massachusetts in Worcester, says the link is plausible. Mounting evidence shows that children with the disorder are more prone to allergies and autoimmune ailments, Barkley says. Moreover, because ADHD is at least partly due to problems with dopamine, an immune gene flaw that interrupts that messaging system connects two dots.

"It's all very tentative, but their results are not farfetched," he says.

To date, the most compelling genetic link to ADHD has been the association between a dopamine gene mutation and the behavior disorder. Barkley says he knows of at least 16 labs that are exploring the molecular genetics of ADHD.

"There are many sub-types [of ADHD], and it's likely that different genes are going to be related to different variations of the disorder," he says.

In the latest study, Ronen Segman, a psychiatrist at Hadassah-Hebrew University Medical Center in Jerusalem, and his colleagues looked for genes tied to ADHD in 86 children with the condition and their parents. They saw that a particular gene variation in IL-1 receptor antagonists (IL-1Ra) -- molecules that prevent brain cells from interacting with interleukin -- was commonly transmitted to affected children.

They also saw that children with ADHD were less likely to inherit a different form of the receptor-blocker gene, suggesting that gene might have a protective effect.

Dr. Julio Lucinio, a psychiatrist at the University of California in Los Angeles, discovered in 1991 that the brain produced its own interleukin antagonists, leading him to speculate that the substances might play a role in mental disorders.

Lucinio, who now edits Molecular Psychiatry, says the Israeli discovery could lead to new therapies for ADHD, although it may be the case that once the mutation occurs, damage to the brain's interleukin system is irreversible. On the other hand, he says, ADHD is marked by spurts of disruptive behavior and it might be possible to even those out with a drug that compensates for the gene variations.

The Israeli researchers looked only at how frequently these genes were passed from parent to child, not how common they are in the general population. So it's impossible to know what percentage of patients with ADHD carry the suspect variation. "I think that future work should try to look at what is the contribution of this variation to ADHD," Lucinio says.

Dr. Pierandrea Muglia, a University of Toronto psychiatrist who specializes in the genetics of mental and behavioral disorders, says the Israeli work underscores the importance of taking a broad view of the origins of ADHD.

"The brain is wired in a very complicated way, so every system might be implicated in some way," Muglia says. However, he adds that the study's relatively small size and the likely modest effect of the gene variations on the risk of ADHD dilute the strength of its conclusions.

What To Do

ADHD can persist into adulthood if untreated. To learn more about the condition, visit Children and Adults with Attention-Deficit/Hyperactivity Disorder.

You can also try the National Institute of Neurological Disorders and Stroke.

SOURCES: Interviews with Russell Barkley, Ph.D., professor, psychiatry and neurology, University of Massachusetts Medical School, Worcester, Mass.; Julio Lucinio, M.D., professor, psychiatry and medicine, University of California at Los Angeles; Pierandrea Muglia, M.D., CIHR post-doctoral research fellow, University of Toronto; January 2002 Molecular Psychiatry
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