A new theory on autism put forward 自閉症新觀點

A new theory on autism put forward

1. April 2009 20:54

Scientists at Albert Einstein College of Medicine of Yeshiva University have

proposed a sweeping new theory of autism that suggests that the brains of

people with autism are structurally normal but dysregulated, meaning

symptoms of the disorder might be reversible.

The central tenet of the theory, published in the March issue of Brain Research

Reviews , is that autism is a developmental disorder caused by impaired

regulation of the locus coeruleus, a bundle of neurons in the brain stem that

processes sensory signals from all areas of the body.

The new theory stems from decades of anecdotal observations that some autistic

children seem to improve when they have a fever, only to regress when the fever

ebbs. A 2007 study in the journal Pediatrics took a more rigorous look at fever

and autism, observing autistic children during and after fever episodes and

comparing their behavior with autistic children who didn't have fevers. This study

documented that autistic children experience behavior changes during fever.

"On a positive note, we are talking about a brain region that is not irrevocably

altered. It gives us hope that, with novel therapies, we will eventually be able to

help people with autism," says theory co-author Mark F. Mehler, M.D., chairman

of neurology and director of the Institute for Brain Disorders and Neural

Regeneration at Einstein.

Autism is a complex developmental disability that affects a person's ability to

communicate and interact with others. It usually appears during the first three

years of life. Autism is called a "spectrum disorder" since it affects individuals

differently and to varying degrees. It is estimated that one in every 150 American

children has some degree of autism.

Einstein researchers contend that scientific evidence directly points to the locus

coeruleus–noradrenergic (LC-NA) system as being involved in autism. "The LCNA

system is the only brain system involved both in producing fever and

controlling behavior," says co-author Dominick P. Purpura, M.D., dean emeritus

and distinguished professor of neuroscience at Einstein.

The locus coeruleus has widespread connections to brain regions that process

sensory information. It secretes most of the brain's noradrenaline, a

neurotransmitter that plays a key role in arousal mechanisms, such as the "fight

or flight" response. It is also involved in a variety of complex behaviors, such as

attentional focusing (the ability to concentrate attention on environmental cues

relevant to the task in hand, or to switch attention from one task to another). Poor

attentional focusing is a defining characteristic of autism.

"What is unique about the locus coeruleus is that it activates almost all higherorder

brain centers that are involved in complex cognitive tasks," says Dr.

Mehler.

Drs. Purpura and Mehler hypothesize that in autism, the LC-NA system is

dysregulated by the interplay of environment, genetic, and epigenetic factors

(chemical substances both within as well as outside the genome that regulate the

expression of genes). They believe that stress plays a central role in

dysregulation of the LC-NA system, especially in the latter stages of prenatal

development when the fetal brain is particularly vulnerable.

As evidence, the researchers point to a 2008 study, published in the Journal of

Autism and Developmental Disorders, that found a higher incidence of autism

among children whose mothers had been exposed to hurricanes and tropical

storms during pregnancy. Maternal exposure to severe storms at mid-gestation

resulted in the highest prevalence of autism.

Drs. Purpura and Mehler believe that, in autistic children, fever stimulates the LCNA

system, temporarily restoring its normal regulatory function. "This could not

happen if autism was caused by a lesion or some structural abnormality of the

brain," says Dr. Purpura.

"This gives us hope that we will eventually be able to do something for people

with autism," he adds.

The researchers do not advocate fever therapy (fever induced by artificial

means), which would be an overly broad, and perhaps even dangerous, remedy.

Instead, they say, the future of autism treatment probably lies in drugs that

selectively target certain types of noradrenergic brain receptors or, more likely, in

epigenetic therapies targeting genes of the LC-NA system.

"If the locus coeruleus is impaired in autism, it is probably because tens or

hundreds, maybe even thousands, of genes are dysregulated in subtle and

complex ways," says Dr. Mehler. "The only way you can reverse this process is

with epigenetic therapies, which, we are beginning to learn, have the ability to

coordinate very large integrated gene networks."

"The message here is one of hope but also one of caution," Dr. Mehler adds.

"You can't take a complex neuropsychiatric disease that has escaped our

understanding for 50 years and in one fell swoop have a therapy that is going to

reverse it — that's folly. On the other hand, we now have clues to the

neurobiology, the genetics, and the epigenetics of autism. To move forward, we

need to invest more money in basic science to look at the genome and the

epigenome in a more focused way."

http://www.aecom.yu.edu/

Souce: http://www.news-medical.net/news/2009/04/01/47775.aspx