MSNBC: A Terrible Mystery

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*http://www.msnbc.msn.com/id/15792806/site/newsweek/

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*MSNBC Newsweek

*A Terrible Mystery

**New clues and new questions in the hunt for a cause.

*By Carmichael

Nov. 27, 2006 issue - * Insel spent years training as a

psychiatrist in the 1970s, and in all that time he saw not one child

with autism. In 1985, curiosity sent him searching; it took several

phone calls to find a single patient. *His only prior exposure to the

disorder was a lecture in which Bruno Bettelheim " explained that it was

due to evil mothers. " The '70s were, he says, " an era of psychiatry that

had no science. "

Today's psychiatry has science˜and it /is/ science˜and increasingly, it

is offering hope for patients with autism. As director of the National

Institute of Mental Health, Insel now heads an agency that funds autism

research all over the nation and also conducts projects of its own.

Thanks to revolutions in neuroscience and genetics, scientists are

starting to unravel the shroud of mystery that has hung over autism

since it was first described in 1943. But with each new discovery, more

questions arise.

That includes the most fundamental question of all: what is autism?

Although the basic symptoms are well defined, researchers are now trying

to categorize the secondary ones, a suite so varied that Insel's

colleagues have started referring to the disease as " autisms. " Some

children with the disorder never speak. Others " are so fluent that you

can't shut them up, " says Spence, a pediatric neurologist at the

NIMH. About 20 percent of kids with autism hit early developmental

milestones but regress around 15 to 18 months; the rest don't make it

that far. What binds them all together is largely unclear.

But autism is known to be highly heritable, and last month, in what was

viewed as a major breakthrough, Vanderbilt University's Pat Levitt

identified the first common gene that plays a role. The MET gene helps

build the brain in utero and in childhood. A faulty variant appears in

47 percent of the population, the vast majority of whom are healthy˜but

a child who carries that variant also carries more than double the risk

of the disease. Another, rarer gene, also implicated in brain

development, was identified in August, and mutations on almost every

chromosome have been suggested as possible culprits, including some

implicated in rare disorders related to autism, such as Rett's Disorder

and Fragile X. " There are perhaps hundreds of different causes, and I

think the field is finally coming to grips with that, " says UCLA

neurogeneticist Dan Geschwind.

The NIMH is also newly interested in *environmental factors *that might

set off the disorder in patients who are already genetically prone to

it. U.S. scientists recently teamed up with counterparts in Denmark and

Norway to screen samples of blood and amniotic fluid for possible

toxins. And research is underway to see if viruses might be involved.

Scientists have also recently found several regions of the brain that

differ from the norm in patients with autism, but none of them appears

to be the sole problem. The key to the disorder likely lies not in one

region but in the way the brain is wired. Some researchers pin the

problem on defects in the brain's decentralized " mirror neuron " network,

which allows healthy people to feel empathy. Other work shows that

distant parts of the autistic brain are connected by too few fibers,

while areas close to each other are connected by too many, tangled in

thickets of " white matter. "

*The ultimate goal of all the research is to find not just a cause but a

cure.* Early behavioral therapy can produce stunning results, and

parents have embraced it˜the intensive clinic at UCLA has an 18-month

waiting list. Still, says Insel, " it's hard to imagine that with a

disease this disabling there's been nothing but behavioral treatments. "

Although few drug companies conducted promising trials this year,

researchers are studying the antibiotic minocycline, the maternal

hormone oxytocin, the drug Ecstasy, and a host of other candidates. *The

NIMH has also just begun a trial of chelation, a process that draws

heavy metals out of the body. The therapy is popular among parents who

maintain that mercury from vaccines prior to 1999 plays a role in

autism˜despite scientists' assurances that it doesn't. " The hypothesis

is difficult to support, " says Swedo, the NIMH's chief of

pediatrics and developmental neuropsychology. " But the anecdotal

evidence is overwhelming. If this works, I want to know why. " Thousands

of scientists, parents and patients do too.

*