Research
On this page you will find articles and links to
current research into or related to Attention Deficit/Hyperactivity Disorder. This is
provided to give you the visitor information as to what is currently being done in this
area. It only contains information about research that we know of and does not constitute
a complete list of everything going on in this field. Please also note that by providing
this information, it does not necessarily mean that adders.org or Thanet ADDers agree or
disagree with any article.
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Serotonin May Hold Key to Hyperactivity Disorder Disorder Treatment
Paying Attention
Treating Children's Sleep Disorders Improves Attention Deficit Symptoms
Serotonin May Hold Key to Hyperactivity Disorder
Disorder Treatment
The following is an extract from Howard Hughes Medical Institute News. Please visit their web site for
more information.
January 15, 1999—Much concern has been raised over
prescribing Ritalin® or other stimulants to control hyperactivity disorders in children.
Relatively little is known about the long-term effects of these stimulants or how they
alter brain chemistry.
Researchers at the Howard Hughes Medical Institute at Duke University
have discovered that Ritalin® and other stimulants exert their paradoxical calming
effects by boosting serotonin levels in the brain. Elevating serotonin appears to restore
the delicate balance between the brain chemicals dopamine and serotonin and calms
hyperactivity, says HHMI investigator Marc Caron at
Duke University Medical Center. Caron is an author of the study published in the January
15, 1999, issue of the journal Science.
Attention deficit hyperactivity disorder (ADHD) affects three to six
percent of school-aged children. Symptoms include restlessness, impulsiveness, and
difficulty concentrating. Stimulants commonly used to treat ADHD are so effective that
"researchers haven't really taken the time to investigate how they work," says
Caron.
Previous dogma, says Caron, held that the calming action of Ritalin®
works through the neurotransmitter dopamine. Specifically, researchers believed that
Ritalin® and other stimulants interact with the dopamine transporter protein (DAT), a
housekeeper of sorts for nerve pathways. After a nerve impulse moves from one neuron to
another, DAT removes residual dopamine from the synaptic cleft-the space between two
neurons-and repackages it for future use.
Caron's team suspected that dopamine wasn't the only key to
understanding ADHD, so they turned to mice in which they had "knocked out" the
gene that codes for DAT. Since there is no DAT to "mop up" dopamine from the
synaptic cleft, the brains of the mice are flooded with dopamine. The excess dopamine
causes restlessness and hyperactivity, behaviors that are strikingly similar to those
exhibited by children with ADHD.
When placed in a maze that normal mice negotiate in less than three
minutes, the knockout mice became distracted-performing extraneous activities such as
sniffing and rearing-and they failed to finish in less than five minutes. The knockout
mice also seemed unable to suppress inappropriate impulses-another hallmark of ADHD.
Surprisingly, the knockout mice were still calmed by Ritalin®,
Dexedrine® and other stimulants even though they lacked the protein target on which
Ritalin® and Dexedrine® were thought to act. "That caused us to look for other
systems that these stimulants might affect," says Caron.
To test whether the stimulants interact with dopamine through another
mechanism, the researchers administered Ritalin® to the normal and knockout mice and
monitored their brain levels of dopamine. Ritalin® boosted dopamine levels in the normal
mice, but it did not alter dopamine levels in knockout mice. That result implied that
"Ritalin® could not be acting on dopamine," says Caron.
Next, the researchers gave the knockout mice a drug that inactivates
the norepinephrine transport protein. With transport disabled, norepinephrine levels
increased as expected, but the boost in norepinephrine did not ameliorate the symptoms of
ADHD as it should. This suggested to Caron's team that Ritalin® exerted its effects
through another neurotransmitter.
They then studied whether the stimulants altered levels of the
neurotransmitter serotonin. The scientists administered Prozac®-a well-known inhibitor of
serotonin reuptake-to the knockout mice. After ingesting Prozac®, the knockout mice
showed dramatic declines in hyperactivity.
"This suggests that rather than acting directly on dopamine, the
stimulants create a calming effect by increase serotonin levels," Caron says.
"Our experiments imply that proper balance between dopamine and
serotonin are key," says Raul Gainetdinov, a member of Caron's research team.
"Hyperactivity may develop when the relationship between dopamine and serotonin is
thrown off balance."
The brain has 15 types of receptors that bind to serotonin, and
Gainetdinov is now trying to determine which specific serotonin receptors mediate the
effects of Ritalin®.
The hope, says Caron, "is that we can replace Ritalin® with a
very specific compound that targets a single subset of receptors." While Prozac®
calmed hyperactivity in the knockout mice, Gainetdinov says that "Prozac® isn't the
best, because it isn't very selective." Caron and Gainetdinov are optimistic that a
new generation of compounds that interact more specifically with the serotonin system will
prove to be safer and more effective for treatments for ADHD.
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Paying Attention
The following are extracts from the Scientific American
website in an "In Focus" article, entitled "Paying Attention". Please
visit their website for the full article.
"......Alan Zametkin of the National Institute of Mental Health
(NIMH) has found, that a small subset of ADHD people have a different receptor for thyroid
hormone and that 70 to 80 percent of all people with this very rare difference in their
thyroid receptor have ADHD.
Other studies have found an association between ADHD and three genes
encoding receptors for the neurotransmitter dopamine......
Neurochemistry is not the whole story. Scientists have also discovered
structural abnormalities. F. Xavier Castellanos of the NIMH used magnetic resonance
imaging to measure the total brain volume and several different brain regions in 57 ADHD
boys and 55 healthy control subjects. His team found that the anterior frontal part of the
brain was on average more than 5 percent smaller on the right side in ADHD boys. The right
caudate and the globus pallidus, too, were smaller. These structures form the main neural
circuit by which the cortex inhibits behavior, and so damage there might well manifest
itself as a lack of impulse control. Castellanos warns that this result offers but part of
the puzzle: "It's only slightly better than phrenology. Now we're just measuring the
bumps on the inside of the brain."
Another facet of ADHD malfunctioning comes from positron emission
tomography (PET) studies. Julie B. Schweitzer of Emory University monitored brain activity
in ADHD and unaffected men while they completed a task. Participants heard a series of
numbers, one every 2.4 seconds, and were asked to add the last two digits they heard.
Looking at the PET scans, Schweitzer saw two major differences between the groups. First,
the ADHD individuals maintained high levels of blood flow, whereas the controls displayed
deactivation in the temporal gyrus region-indicating some kind of learning."
Our thanks to Carol T. for bringing this to our attention.
[Back To Top Menu]
Treating Children's Sleep Disorders Improves Attention
Deficit Symptoms
Description: By treating children's sleep disorders, parents may find
that their attention deficit hyperactivity disorder (ADHD) improves as well, according to
a new study.
Treating Children's Sleep Disorders Improves Attention Deficit Symptoms
By treating children's sleep disorders, parents may find that their attention deficit
hyperactivity disorder (ADHD) improves as well, according to a study released during the
American Academy of Neurology's 50th Anniversary Annual Meeting April 25-May 2 in
Minneapolis, MN.
The study involved children with ADHD as well as restless legs syndrome
and/or periodic limb movements of sleep. ADHD is a chronic, neurologically based syndrome
characterized by restlessness, distractibility and impulsivity. Restless legs syndrome is
a neurological disorder characterized by sensations of discomfort in the legs during
periods of inactivity relieved by moving or stimulating the legs. Periodic limb movements
of sleep involves episodes of repetitive leg movements causing brief awakenings in brain
activity. Both sleep disorders can cause interrupted sleep and fatigue or sleepiness
during the day.
In the study, five children were treated with the drug levodopa, which
has been shown to improve symptoms of these sleep disorders but not ADHD.
"The children showed marked improvement," said neurologist
Arthur S. Walters, MD, of the UMDNJ-Robert Wood Johnson Medical School and Lyons VA
Medical Center in New Brunswick, NJ. "Their sleep disorders improved, and so did
their behavior and mental acuity."
The children's attention spans improved, along with their memory. And
parents also reported that their children's behavior improved.
Walters said the sleep disruption may cause the children to be
inattentive and hyperactive due to sleep deprivation. The children also may have leg
discomfort when sitting at their school desks that is relieved only by moving around, he
said.
Walters cautioned, "It is not definitely proven that periodic limb
movements of sleep leads to symptoms of ADHD. An alternative possibility is that these
disorders simply appear together frequently."
Children with ADHD have a higher incidence of periodic limb movements
of sleep than children who don't have ADHD, Walters said. Also, the parents of children
with ADHD and periodic limb movements of sleep have a higher incidence of restless legs
syndrome than other parents.
Researchers also have another theory why levodopa improves the
children's ADHD symptoms.
"There may be a common link -- a dopaminergic deficiency in the
brain that causes both the sleep disorders and the ADHD," Walters said.
One argument supporting this theory is that Ritalin), a common
treatment for ADHD, promotes dopamine action in the brain, as does levodopa. "No one
understands why a stimulant -- Ritalin(r) -- improves hyperactive behavior," Walters
said. "This could be why."
Walters said the benefits of the levodopa appear to last long term. The
next step to confirm these results is a double-blind, placebo-control trial, he said. The
drug should also be tested with children with ADHD who do not have these sleep
disturbances, he said. Our thanks to Kathy West for bringing this to our
attention.
COMMENT
Dr.Billy Levin writes in reaction to the above article....
"There is a very clear association between A.D.H.D. and sleep
disturbances starting with the infant who just does not sleep until he is exhausted. ,
followed by the toddler who won't go to sleep on his own or will only sleep in the parents
bed. The young child who is afraid of the dark, or takes ages to fall asleep or a very
restless sleeper. The older child may go late to bed, have nightmares or wake at the crack
of dawn. Separation anxieties may manifest here or bed wetting. All these to a greater or
lesser degree and some or all may present.
As to Ritalin, the stimulating effect, boosts the immature inhibitory
function on the left hemisphere giving the patient on treatment better "brakes".
When many young A.D.H.D patients are given a sedative the opposite takes place. That is,
they are stimulated and hyperactivity gets worse. Clearly the inhibitory centers on the
left hemisphere are sedated with fewer "brakes" and more activity takes place.
This is the well known "paradoxical reaction" often seen, to medications, in
these children. ADHD must be seen as an over developed right hemisphere giving behavior
problems or and immaturity of the left hemisphere giving rise to learning problems or a
mixture of both in varying degrees." [Back To Top Menu]
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