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March 22, 2007-Forwarded by Elise Miller- CHE-LDDI

Autism: It's Not Just in the Head

The devastating derangements of autism also show up in the gut and in the
immune system. That unexpected discovery is sparking new treatments that
target the body in addition to the brain.

by Jill Neimark, Discover

Article Summary:
Autism, traditionally seen as genetic and originating in the brain, is
starting to be viewed in a broader and very different light, as a possible
immune and neuroinflammatory disorder. As a result, autism is beginning to
look like a condition that can, in some and perhaps many cases, be
successfully treated. A disparate group -- immunologists, naturopaths,
neuroscientists, and toxicologists -- is turning up clues that are yielding
novel strategies to help autistic patients.

New studies are examining contributing factors ranging from vaccine
reactions to atypical growth in the placenta, abnormal tissue in the gut,
inflamed tissue in the brain, food allergies and disturbed brain wave
synchrony. Some clinicians are using genetic test results to recommend
unconventional nutritional therapies, and others employ drugs to fight
viruses and quell inflammation.

Above all, there is a new emphasis on the interaction between vulnerable
genes and environmental triggers, along with a growing sense that low-dose,
multiple toxic and infectious exposures may be a major contributing factor
to autism and its related disorders. One can distill a few revolutionary
insights from among the many potential avenues of research. First, autism
may not be rigidly determined but instead may be related to common gene
variants, called polymorphisms, that may be derailed by environmental
triggers. Second, affected genes may disturb fundamental pathways in the
body and lead to chronic inflammation across the brain, immune system, and
digestive system. Third, inflammation is treatable.

Harvard pediatric neurologist Martha Herbert has authored a 14,000-word
paper in the journal Clinical Neuropsychiatry that reconceptualizes the
universe of autism, pulling the brain down from its privileged perch as an
organ isolated from the rest of the body. "What I believe is happening is
that genes and environment interact, either in a fetus or young child,
changing cellular function all over the body, which then affects tissue and
metabolism in many vulnerable organs. And it's the interaction of this
collection of troubles that leads to altered sensory processing and impaired
coordination in the brain. A brain with these kinds of problems produces the
abnormal behaviors that we call autism."

Each child's path to autism may be distinct, she says, but they may share
common inflammatory abnormalities. She has shown through morphometric brain
imaging that white matter -- which carries impulses between neurons -- is
larger in children with autism. If white matter is chronically inflamed,
then one potential treatment approach is to down-regulate the brain's immune

Jill James, director of the Autism Metabolic Genomics Laboratory at the
Arkansas Children's Hospital Research Institute (and professor of pediatrics
at the University of Arkansas for Medical Sciences) has found that many
children with autism do not make as much of a compound called glutathione as
neurotypical children do. Glutathione is the cell's most abundant
antioxidant, and it is crucial for removing toxins. If cells lack sufficient
antioxidants, they experience oxidative stress, which is often found with
chronic inflammation. Oxidative stress in some autistic children may be
treatable with targeted nutritional intervention.

Genetic vulnerability -- related to immune system, brain, and gut -- must
also be considered. Pat Levitt, director of the Vanderbilt Kennedy Center
for Research on Human Development, and his colleagues recently discovered
that a common variant of a gene called MET doubles the risk of autism. The
finding was widely regarded as a breakthrough because MET modulates the
nervous system, gut, and immune system -- just the kind of finding that
matches up with the emerging new view of autism.

The gene variant occurs in 47 percent of the population -- in other words,
it is just one contributing factor, and it probably works in concert with
other vulnerability genes. The activity of the gene is affected by what is
known as oxidative stress -- the kind of damage one sees with excessive
exposure to toxins. Several large-scale, federally funded epidemiological
studies are under way to pinpoint possible environmental triggers, as well
as early biomarkers of autism. The trick is to build a large enough study to
be able to look at both genes and environment together. An ambitious study,
called the Autism Birth Cohort, by Columbia University and the Norwegian
Institute of Public Health will follow 100,000 pregnant women for 72 months,
studying their health and genetics and testing everything from blood to
urine samples.

The hope is to discover environmental factors that contribute to autism
risk, from diet or infection to toxins like heavy metals, pesticides, and
the countless synthetic molecules in products today. Other large NIH- and
EPA-funded studies are teasing out immune abnormalities that may contribute
to autism.

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