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Antidepressants can Break Through The Wall of Many Children's Autism, Duke Researchers say

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Duke Health News 919-660-1306

DURHAM, N.C. - Many autistic children may actually suffer
from a genetically linked depression that is treatable with
antidepressants such as Prozac (fluoxetine), according to Dr.
Robert DeLong, a Duke University Medical Center pediatric
neurologist.

In an article in the March 23 issue of the journal
Neurology, DeLong presents a new hypothesis that about
two-thirds of children with the most common form of infantile
autism actually have a treatable, genetically linked,
early-onset form of severe depression. The argument is based on
recent genetic analyses, behavioral studies and brain chemistry
and imaging analyses on autistic children by researchers at
Duke and several other institutions.

The research was funded by the Charles and Sara Goldberg
Charitable Trust and the Duke Children's Telethon.

"Several lines of evidence are now coming together to form a
cohesive picture of the biological basis of a disease that has
long baffled the medical community," said DeLong. "Genetic and
brain imaging studies, as well as a re-examination of the
classical symptoms of autism, all point to the conclusion that
many autistic children have an inherited disease that we know
how to treat."

Children with autism appear to be prisoners of their own
minds because they are unable to learn the language or social
skills necessary to get along in the world.

Autism is actually a spectrum of disorders with similar
symptoms, said DeLong. Children who develop autism, usually in
the second year of life, lose the ability to interact with
people or their environment and don't speak or use language,
even though many have normal intelligence.

While some autism is caused by diseases or injury to certain
areas of the developing brain, most cases of autism have no
known cause, and of these so-called idiopathic cases, DeLong
asserts that 70 percent now appear to be an inherited form of
an affective disorder, such as manic depression or
obsessive-compulsive disorder.

"Many years ago I noticed that if you look carefully at the
symptoms of autism, they look very much like those of
depression and manic depression," said DeLong. "These children
show none or the cheerfulness or spontaneity of normal
children. And they often have extreme moods swings, tantrums
and excessive fearfulness."

DeLong has identified several lines of evidence that
together show a distinct subgroup of autistic children who have
a genetic disease that can be treated with anti-depressive
medications.

When researchers examine the brains of children with
idiopathic autism, they find very low levels of the
neurotransmitter serotonin on the left side of the brain in the
area responsible for language. Serotonin is also important in
influencing mood and is low in people with clinical
depression.

"In the developing brains of children, serotonin not only
acts as a transmitter of information, but it is also an agent
of development that influences growth in the brain," said
DeLong. "When serotonin levels in the left hemisphere of the
brain don't reach a critical level in early childhood, one
might expect to see the symptoms we see in autism: blunting of
the child's cognitive, social and emotional development."

Studies of people in which the connection between the left
and right hemispheres of the brain are split surgically to
relieve symptoms of epilepsy, so-called "split brain"
experiments, show the left hemisphere is responsible for
language and reasoning skills, while the right hemisphere is
responsible for visual-spatial skills, musical ability and some
types of rote memorization. Serotonin levels in the right
hemisphere of most idiopathic autistic children are normal and
their visual and spatial skills are also normal. In fact, some
autistic savants show a type of overcompensation on the right
side of the brain that gives them extraordinary abilities in
math computation, music or artistic skills.

When the researchers studied older children and adolescents
diagnosed with manic depression, they found these children also
have greater visual-spatial abilities and lower language
skills, although the differences were not as great as in
autistic children.

All these lines of evidence led DeLong to try treating
autistic children with Prozac and other specific serotonin
re-uptake inhibitors (SSRIs). These medications, well known for
treating depression, work by making more serotonin available to
the brain.

In a study reported in the October 1998 issue of the Journal
of Developmental Medicine and Child Neurology, DeLong and his
colleagues showed that when 37 autistic children ages three to
seven were treated with Prozac (fluoxetine) for up to three
years, 22 responded well to the medication, regaining language
abilities, becoming more sociable and losing obsessive
compulsions such as fixating on a single object for hours on
end. Of those children who responded to the medication, all had
a family history of a major depressive disease, such as bipolar
disorder.

"It is tempting to say that autism and manic depression are
caused by a defect in the same gene," said DeLong, "and genetic
evidence is beginning to point in that direction."

Recent studies by DeLong and his colleagues at Duke point to
a gene somewhere on chromosome 15 as a potential autism gene.
And now several studies by investigators at other institutions
studying manic depression have narrowed down their search to
the same general area on chromosome 15 as well.

"While we can't yet definitively say that the genes are one
and the same, the evidence is tantalizing, and we expect to
have answers in the near future," said DeLong.

Such genetic studies offer hope of an earlier diagnosis,
said DeLong, and the development of more specific medications
to increase the availability of serotonin in the developing
brains of autistic children offers the hope of even more
effective treatment for the disease.

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