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A Neurological Basis for ADHD

http://www.technologyreview.com/Biotech/19197/page1/

Scientists have identified a genetically determined pattern of brain

development linked to ADHD.

By Singer

A genetic variation that boosts risk for Attention Deficit Hyperactivity

Disorder (ADHD) paradoxically appears to predict who will grow out of the

learning disability. Scientists found that brain development in ADHD-afflicted

children with this variation was out of whack at age 8 but normalized by 16.

ADHD symptoms in this group were also more likely to disappear with age. The

study is the first to identify a genetically determined pattern of brain

development linked to ADHD and indicates a real neurological basis for the

disorder, which has been viewed by some as a contrivance of pharmaceutical

marketers or the product of bad parenting.

ADHD brains: Scientists found that children with ADHD who had a

particular genetic variation started out with an unusually thin cortex in the

parts of the brain important for attention. But over time, their brains became

indistinguishable from those of healthy teens. This time-lapse series of images

shows how their brains normalized over time--the brightly colored sections

indicate the parts of the brain that were most different in the ADHD group.

These sections disappear as the children aged.

Credit: Philip Shaw, M.D., NIMH Child Psychiatry Branch

" This is the first step in individualizing treatment for ADHD based on genetic

make-up, " says Philip Shaw, a neuroscientist at the National Institute of Mental

Health in Bethesda, MD, who led the study.

ADHD is one of the most common childhood disorders in the United States,

affecting about three to five percent of school-aged kids. Scientists have

already uncovered several genetic variations that raise risk for ADHD, which is

likely caused by a complex combination of genetic and other factors. The biggest

genetic culprit identified to date is a variation in a receptor for

dopamine--one of the brain's signaling molecules--which increases risk for the

disorder by 20 to 30 percent.

To try to understand how this variation influences attention, Shaw and

colleagues scanned the brains of 105 children with ADHD and 103 healthy controls

between 8 and 16 years old, repeating the scans in a subset of children through

their teen years. They also determined how many copies, if any, the children

carried of the target variation.

Scientists found that ADHD-afflicted children with the high-risk genetic

variation seemed to be worst off at younger ages--parts of the cortex crucial

for attention were thinner in this group than in both their normal counterparts

and in children with ADHD lacking that variation. However, the high-risk variant

group also showed the best chance of recovery. In contrast to other children

with ADHD, the cortices of these children naturally normalized by age 16. Like

gangly teenagers growing into their too-long limbs, they were also most likely

to have grown out of their ADHD symptoms. " People who have the risk gene have a

distinctive pattern of brain growth that normalizes with age, " says Shaw. " That

might be what's driving the good clinical outcome they have. " The findings were

published this week in the Archives of General Psychiatry.

Scientists don't yet know exactly how this genetic marker contributes to

differences in brain size or in behavior. But previous research has shown that

receptors with the variation don't respond to dopamine as effectively as other

forms of the gene. " That biological action of the brain may help to explain why

in this study, the cortical thickness was thinner in the people who carried this

variant, " says Kennedy, professor of psychiatry at the University of

Toronto. " The reasoning would be that people with that allele would have a bit

less nerve transmission activity in areas of their brain where this is located. "

Kennedy likens grey matter in the brain to muscle, which gets bigger with

exercise. " The more you use it, the more synapses are formed and the more volume

is created. "

Shaw and others caution that it's too early to use the findings to diagnose

the disorder or to influence treatment. " But with more research, it may be

possible to do an MRI study before starting medication and then predict what

type of treatment might be best for that individual based on their brain image

and genotype, " says Kennedy.

The findings may also help quell some controversy surrounding the disorder.

ADHD is diagnosed mainly by a child's behavior, and some have argued that pushy

pharmaceutical companies, impatient parents and overburdened teachers have led

to chronic overdiagnosis and unnecessary medication of children. Identifying a

mechanism by which a genetic allele might influence ADHD helps solidify a

neurological basis of the disorder.

In addition, the study supports the idea that ADHD sometimes disappears in

adulthood. While that idea had gone out of favor, recent large-scale follow

studies suggest that some children do get better and stay better, says

Swanson, professor of psychiatry at University of California, Irvine. The new

findings may provide a biological basis for this pattern, he says.

He adds that the gene itself is very interesting. The variation linked to ADHD

shows signs that it was selected for during evolution, suggesting that it

confers some kind of advantage. " [The variation] might be linked to a different

way of thinking or acting that is diagnosed as ADHD in childhood but could be

beneficial at other times in development, " says Swanson.

Rick Tallman

Defender of Truth, Justice and the American way

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Hmmmm.

The second of many that turn up when you google mercury and dopamine.

I don't suppose these researchers bothered to do porphyrin tests on any of their

test

subjects?

Sue

http://www.chem-tox.com/pregnancy/mercury.htm

Dopamine Uptake in Brain Cells Changed By Methylmercury

Attention Deficit Disorder children were reported in other headings in this book

as having

altered dopamine levels. Several compounds, including alcohol, have been shown

to alter

dopamine levels in test animals. Now, researchers at Duke University Medical

School have

shown that even very low levels of methylmercury result in dopamine and

norepinephrine

brain neurotransmitter changes.

Litters of rat pups were exposed to methylmercury via drinking water for 21 days

beginning the day after birth. Levels of mercury exposure were 1 mg/kg, 2.5

mg/kg and 5

mg/kg.

Results showed that the uptake of dopamine in the animals brains was 58% under

normal

when the animals were 5 days of age when exposed to the 5.0 mg/kg dose, and

approximately 15% under normal at 10 days of age at the 2.5 mg/kg dose.

Interestingly,

by the time the animals were 32 days old and 11 days after mercury exposure

terminated,

the animalsÕ dopamine uptake levels had now jumped 50-70% above normal levels

and

were considered statistically significant. Similar significant changes were also

seen with

the neurotransmitter norepinephrine.

In summary, the researchers stated,

" These studies show that neonatal methylmercury exposure produces both acute and

long-lasting effects on maturation of central catecholamine neurotransmitter

systems

which may be transmitter specific. In keeping with the behavioral teratology of

this

substance, abnormalities of neurotransmitter biochemistry can be detected at

doses well

below those which suppress growth of the organism (only the 5 mg/kg dose altered

growth parameters, i.e. brain weight).

Dr. Bartolome, Trepanier

Department of Pharmacology, Duke University, North Carolina

Toxicology And Applied Pharmacology 65: 92-99, 1982

>

>

> A Neurological Basis for ADHD

http://www.technologyreview.com/Biotech/19197/

page1/

> Scientists have identified a genetically determined pattern of brain

development linked

to ADHD.

> By Singer

> A genetic variation that boosts risk for Attention Deficit Hyperactivity

Disorder (ADHD)

paradoxically appears to predict who will grow out of the learning disability.

Scientists

found that brain development in ADHD-afflicted children with this variation was

out of

whack at age 8 but normalized by 16. ADHD symptoms in this group were also more

likely

to disappear with age. The study is the first to identify a genetically

determined pattern of

brain development linked to ADHD and indicates a real neurological basis for the

disorder,

which has been viewed by some as a contrivance of pharmaceutical marketers or

the

product of bad parenting.

> ADHD brains: Scientists found that children with ADHD who had a

particular

genetic variation started out with an unusually thin cortex in the parts of the

brain

important for attention. But over time, their brains became indistinguishable

from those of

healthy teens. This time-lapse series of images shows how their brains

normalized over

time--the brightly colored sections indicate the parts of the brain that were

most different

in the ADHD group. These sections disappear as the children aged.

> Credit: Philip Shaw, M.D., NIMH Child Psychiatry Branch

> " This is the first step in individualizing treatment for ADHD based on

genetic make-

up, " says Philip Shaw, a neuroscientist at the National Institute of Mental

Health in

Bethesda, MD, who led the study.

> ADHD is one of the most common childhood disorders in the United States,

affecting

about three to five percent of school-aged kids. Scientists have already

uncovered several

genetic variations that raise risk for ADHD, which is likely caused by a complex

combination of genetic and other factors. The biggest genetic culprit identified

to date is a

variation in a receptor for dopamine--one of the brain's signaling

molecules--which

increases risk for the disorder by 20 to 30 percent.

> To try to understand how this variation influences attention, Shaw and

colleagues

scanned the brains of 105 children with ADHD and 103 healthy controls between 8

and 16

years old, repeating the scans in a subset of children through their teen years.

They also

determined how many copies, if any, the children carried of the target

variation.

> Scientists found that ADHD-afflicted children with the high-risk genetic

variation

seemed to be worst off at younger ages--parts of the cortex crucial for

attention were

thinner in this group than in both their normal counterparts and in children

with ADHD

lacking that variation. However, the high-risk variant group also showed the

best chance

of recovery. In contrast to other children with ADHD, the cortices of these

children

naturally normalized by age 16. Like gangly teenagers growing into their

too-long limbs,

they were also most likely to have grown out of their ADHD symptoms. " People who

have

the risk gene have a distinctive pattern of brain growth that normalizes with

age, " says

Shaw. " That might be what's driving the good clinical outcome they have. " The

findings

were published this week in the Archives of General Psychiatry.

> Scientists don't yet know exactly how this genetic marker contributes to

differences in

brain size or in behavior. But previous research has shown that receptors with

the

variation don't respond to dopamine as effectively as other forms of the gene.

" That

biological action of the brain may help to explain why in this study, the

cortical thickness

was thinner in the people who carried this variant, " says Kennedy,

professor of

psychiatry at the University of Toronto. " The reasoning would be that people

with that

allele would have a bit less nerve transmission activity in areas of their brain

where this is

located. " Kennedy likens grey matter in the brain to muscle, which gets bigger

with

exercise. " The more you use it, the more synapses are formed and the more volume

is

created. "

> Shaw and others caution that it's too early to use the findings to diagnose

the disorder

or to influence treatment. " But with more research, it may be possible to do an

MRI study

before starting medication and then predict what type of treatment might be best

for that

individual based on their brain image and genotype, " says Kennedy.

> The findings may also help quell some controversy surrounding the disorder.

ADHD is

diagnosed mainly by a child's behavior, and some have argued that pushy

pharmaceutical

companies, impatient parents and overburdened teachers have led to chronic

overdiagnosis and unnecessary medication of children. Identifying a mechanism by

which

a genetic allele might influence ADHD helps solidify a neurological basis of the

disorder.

> In addition, the study supports the idea that ADHD sometimes disappears in

adulthood. While that idea had gone out of favor, recent large-scale follow

studies suggest

that some children do get better and stay better, says Swanson, professor

of

psychiatry at University of California, Irvine. The new findings may provide a

biological

basis for this pattern, he says.

> He adds that the gene itself is very interesting. The variation linked to

ADHD shows

signs that it was selected for during evolution, suggesting that it confers some

kind of

advantage. " [The variation] might be linked to a different way of thinking or

acting that is

diagnosed as ADHD in childhood but could be beneficial at other times in

development, "

says Swanson.

>

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> Rick Tallman

> Defender of Truth, Justice and the American way

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