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Autism: A
Study That Discounts a Suspected Cause of the Disorder Gives Way
to More Questions Than Answers
by David Kohn, Baltimore Sun, 2003
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In recent years,
autism research has been a battleground. A vocal group of
parents, advocates and a few scientists focused on vaccines
containing traces of mercury as the lead suspects in the
disorder. But most autism researchers were suspicious, arguing
that the theory didn't fit the evidence.
Now, with a new Danish study offering the strongest evidence yet
against the vaccine theory, the controversy may give way to a
more baffling question: If vaccines aren't the culprit, then
what is? The range of theories underscores how little is known
about autism, a developmental illness that afflicts as many as
one in 200 American children and makes it difficult for them to
connect with the outside world.
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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