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Autism: One More Step on a Long Road

Autism: One More Step on a Long Road

With autism diagnoses rising, researchers hunt for clues that will illuminate the mechanisms behind the disorder. What science knows about the disorder, in fact, is dwarfed by what science has yet to find out. “ There are a lot of different routes to autism,” says William Eaton, PhD, Sylvia and Harold Halpert Professor and chair of the Department of Mental Health. “It has a complex set of etiologies.”

Most in the field agree that autism is perhaps the most strongly inherited mental illness—one out of 20 infants with an autistic sibling will also fall on the spectrum (compared with one out of 150 children in the general population). What’s still debated is how it’s inherited. 

While some forms of autism are purely genetic, there is strong evidence that points toward a congenital cause for other forms. A new study by Eaton and colleagues, published in Pediatrics, supports the theory that some forms of autism are created in utero, by environmental factors triggered by maternal immune system disorders.

Ten years ago, Andrew Zimmerman, MD, associate professor of Neurology, Psychiatry and Pediatrics at the Johns Hopkins School of Medicine, and colleagues published the first study to link autism to an autoimmune disorder—rheumatoid arthritis—in the autistic child’s mother. Since then, further studies have shown evidence of links between autism and two other parental autoimmune disorders, Type 1 diabetes and celiac disease (a disorder of the small intestine). Eaton’s study supports Zimmerman’s findings on rheumatoid arthritis, and it turned up a nearly threefold risk of autism associated with celiac disease in the mother.

“These findings lead us to believe that it may be the fetal environment,” says Eaton. “Something happens in gestation with disruption of the immune system.”

Eaton theorizes that the mother’s celiac disease exposes the fetus to a damaging agent that can cross the placenta and the fetus’s blood-brain barrier. Zimmerman thinks that damaging agent may be maternal antibodies— possibly triggered by autoimmune disorders— that attack the fetus’s brain.

Should women with autoimmune diseases avoid becoming pregnant? Both Eaton and Zimmerman say no. What is important, though, is that women get diagnosed and treated—as much as is possible—for these conditions before becoming pregnant. Disorders such as celiac disease, when untreated, can lead to conditions in the mother that would lead to low birth-weight and other obstetric complications known to increase risk for autism.

Eaton sees several possible next steps, from scouring the literature—and perhaps the genome—for genetic links, to searching further for effects of autoimmunity on the development of the fetus. The recent study underscores the importance of the latter.

“This study has brought us to a new level,” says Zimmerman. “We’ve been struggling for years to bring the importance of the immune system to the fore in autism."

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