Autism: A study that discounts a suspected cause of the disorder gives way to more questions than answers

Researchers are looking at a variety of possible mechanisms: Do
these children suffer from “extreme male” brains? Are they prenatal victims of
their mothers’ overaggressive immune systems? Or does faulty insulation
between neurons fill their brains with maddening static? These are a few
of many competing theories.

“There are a variety of tantalizing trails of evidence,” says Diana
Schendel, a Centers for Disease Control and Prevention epidemiologist who
studies the disorder. “But none of them are conclusive, by any stretch of
the imagination.”

Last week’s issue of Pediatrics published a report on autism cases
in Denmark, which stopped using vaccines containing thimerosal, a common
mercury-based preservative, in 1992. (In the past three years, U.S.
manufacturers also have stopped or reduced thimerosal use in children’s
vaccines.) The Pediatrics study found that Denmark’s autism had risen
sharply since 1992. “If thimerosal causes autism, then you’d expect rates
to go down after it’s banned,” said the study’s main author, Dr. Kreesten
Madsen of the Danish Epidemiology Science Center.
Most autism experts agree with Madsen.

“This reaffirms that there is no evidence that thimerosal causes
autism,” said Dr. Neal Halsey, director of the Institute for Vaccine
Safety at the Johns Hopkins University.

But some critics called Madsen’s study deeply flawed. Because
Denmark has such a low autism rate, the study is irrelevant to the United States,
said Mark Blaxill, a director of the parent group Safe Minds. “We still
consider thimerosal a very important suspect,” he said.

Yet even scientists who suspect thimerosal minimize its role in the
disorder. “If thimerosal was a huge contributor, we would have picked that
up already,” said University of California researcher Isaac Pessah, who is
hunting for chemical triggers, including mercury and pesticides.

Most researchers suspect that autism is a family of disorders with
several causes. While autistic people share a core of symptoms – they
crave routine, have trouble communicating, and don’t understand intuitive social
rules – their behavior can vary greatly. While some have large
vocabularies, others barely speak. Some seem riotously overstimulated; others seem locked in a world with little sensation.

“Autism is no one thing. It probably has multiple causes,” said Dr. Andy Zimmerman of the Kennedy Krieger Institute’s Center for Autism and Related Disorders.

A combination of abnormal genes – probably between four and 20 –
likely lays the groundwork for the illness. Dozens of scientists are
trying to find these oddities. Among these is a group at Vanderbilt University,
which recently found that some autistics have a gene that may decrease
brain serotonin levels. This neurotransmitter plays a role in several key
autistic symptoms, including compulsiveness and anxiety.

But genes alone don’t cause the illness. Most experts think genes
simply create a vulnerability, and that environmental factors send some of
these children over the edge.

Zimmerman, a pediatric neurologist, suspects that immune system
abnormalities in mother and child may provide one push. Several studies
have found that maternal infections during pregnancy can increase a child’s
autism risk. He theorizes that the illness is set in motion when a mother’s aggressive immune response throws off the rhythm of fetal brain development.

In his most recent work, Zimmerman has found that in some autistics, the brain’s immune cells – the microglia – are overactive. His next step: to find out whether these cells are fighting off an attack or doing harm themselves.

At Harvard Medical School, pediatric neurologist Margaret Bauman
has recently found evidence of such subtle brain damage. In studying the
brains of autistic cadavers, she found abnormalities in the “white matter,”
insulation that keeps neuronal messages free of static.

Many scientists think the illness may stem from an oversized brain.
A study published this summer in the Journal of the American Medical
Association found that autistic toddlers had larger than average heads.

This “neuroproliferation” could explain why autistics often seem overwhelmed by
ordinary stimuli.

“There are too many cells, and they could potentially create too much noise,” said Rebecca Landa, director of the Center for Autism. “It’s like sticking your finger in a socket. Their brains can’t channel on the input.”

She is working on a study to measure the levels of neurochemicals
that may control brain size and structure. “Maybe the brain overbuilds itself,”
said Landa, who hopes to correlate neurochemical levels with specific
autistic behavior.

Other scientists are focusing not on the size of the autistic
brain, but its gender. Cambridge University psychiatrist Simon Baron-Cohen argues
that those with the illness have “extreme male brains.”

Men, he says, tend to see the world in terms of systems, while women view it through the prism of emotion and relationship. Autistics – 80 percent of whom are male – show many hyper-masculine traits, he argues.

They focus on details while neglecting the whole, have trouble interpreting
facial expressions and acquire language slowly. He has also found high rates of autism in families of physicists and engineers – professions that require systematizing skill.

Baron-Cohen is testing testosterone levels in the amniotic fluid of 3,000 children, some of them autistic. His hypothesis: high prenatal testosterone can produce an acutely “male” brain. The hormone may speed development of the right hemisphere, which probably controls these male characteristics.

If testosterone does play a role, prenatal treatments might help the disease. But Baron-Cohen is leery, arguing that “hormonal engineering” could radically alter personality.

“Would we want to intervene?” he asked. “You may make your child more sociable, but also maybe less focused on systems. There could be a cost for that.”

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