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Discovery Magazine, Autism, It's Not Just In the Head

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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

March 22, 2007

http://discovermagazine.com/2007/apr/autism-it2019s-not-just-in-the-head

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

response.

Jill , 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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