Tourette Updates

Mecamylamine Relieves Depression in Children With Tourette's Syndrome
Source: University of South Florida College of Medicine
A well-tolerated drug that blocks nicotine receptors in the brain
appears to relieve depression and mood instability in children and
adolescents with Tourette's syndrome, a preliminary study by
University of South Florida College of Medicine researchers has
found.

The multicenter, placebo-controlled study of the drug mecamylamine
is published in the latest issue of the journal Depression and
Anxiety.

"These preliminary findings are consistent with anecdotal
observations that mecamylamine stabilizes mood," said lead author
Douglas Shytle, PhD, assistant professor in the USF Departments of
Neurosurgery and Psychiatry. "In addition, this is the first
clinical evidence supporting the hypothesis that many
antidepressants function, in part, by inhibiting nicotinic
receptors."

Dr. Shytle emphasized that larger clinical studies are needed to
determine if nicotine antagonists like mecamylamine would provide a
new avenue for treating depression and other mood disorders.

In a 1998 study, the USF researchers reported that small doses of
mecamylamine (trade name Inversine(TM)), a drug originally used to
treat hypertension, seemed to reduce the rage reactions and
irritability that many children with Tourette's experience.

In this national randomized study, the researchers examined the
effect of mecamylamine on symptom improvement in a group of 50
children and adolescents co-diagnosed with Tourette's syndrome and
at least one of several mood disorders. The mood disorders were
major depression, attention deficit hyperactivity disorder (ADHD),
oppositional defiance disorder, obsessive compulsive disorder, and
hypomania.

Of the 50 participants, 38 completed the full 8-week trial -- 17 on
mecamylamine and 21 receiving a placebo pill.

The four Tourette's patients co-diagnosed with major depression
showed the greatest mecamylamine-related improvements in behavioral
and emotional symptoms, including significant decreases in sudden
mood changes, irritability, demanding attention, inattention,
restlessness, anxiety and impulsiveness. The medication's most
beneficial effect appeared to be stabilizing mood.

The depressed patients treated with the placebo showed no benefit.

In a report published this summer in the journal Molecular
Psychiatry, the USF researchers suggest that many newer, more
selective antidepressants such as Prozac work, in part, by
inactivating nicotine receptors in the brain. These receptors appear
to be overstimulated by the biochemical messenger acetylcholine in
patients who are depressed.

The most common current explanation for how antidepressants work is
by boosting levels of serotonin, a brain biochemical that is low in
people with depression.

"Our preliminary findings with mecamylamine suggest that another way
antidepressants may improve depressed moods is by blocking
acetylcholine's excess activation of nicotine receptors," said
investigator Paul R. Sanberg, PhD, DSc, professor and director of
the USF Neuroscience Program.

"It allows us to explore a new class of drugs for neuropsychiatric
disorders," said investigator Archie Silver, MD, director of the USF
Center for Infant and Child Development.

The USF research team recently started a controlled study of
mecamylamine in children and adolescents with bipolar disorder, also
known as manic depression. This latest study is funded in part by
the Stanley Medical Research Institute.

Other authors of study in Depression and Anxiety were Kathy Sheehan,
PhD; and David Sheehan, MD.

The study was supported in part by a grant from the USF High-Tech
Corridor Project. The researchers got mecamylamine through Layton
BioScience, Inc., a California biotechnology firm that owned rights
to the medication at the time of the study.

Mecamylamine (Inversine(TM)) is now owned and marketed by Targacept,
a Salem, NC pharmaceutical company that licenses USF's patent
covering the use of nicotine antagonists for the treatment of
neuropsychiatric disorders."

Reference:

Shytle RD, Silver AA, Sheehan KH, Sheehan DV, Sanberg PR. Neuronal
nicotinic receptor inhibition for treating mood disorders:
preliminary controlled evidence with mecamylamine. Depression and
Anxiety, 2002;16(3):89-92


Copyright © 2002 Acurian Inc. All Rights Reserved.

##########################################



Reported July 21, 2003
Depression Risk in the Genes
(Ivanhoe Newswire) -- Why do some people become depressed after a
stressful event while others don't? New research suggests it could
be a specific version of a gene.
Researchers from Wisconsin and London followed more than 800
participants from birth into adulthood. Seventeen percent of the
participants carried two copies of a short version of the serotonin
transporter gene, about 30 percent carried two copies of a long
version of the gene, and about 50 percent carried one copy of each
version of the gene.
Results of the study show more than 40 percent of the participants
carrying two short genes suffered from depression following a
traumatic life event. Less than 20 percent of those with long genes
developed depression after a stressful event. Researchers define
a "stressful event" as losing a job, having a loved-one die, being
diagnosed with a serious illness, or experiencing a break-up or
divorce.
Terrie Moffitt, Ph.D., from the University of Wisconsin and King's
College in London, says, "We found the connection [between the gene
version and depression] because we looked at the study members'
stress history."
Everyone inherits two copies of the serotonin transporter gene, one
copy from each parent. Each version of the gene functions
differently. The short version makes less protein, resulting in
increased levels of serotonin. Researchers say this may be why it
appears less efficient at stopping unwanted messages.
Participants with the short genes who had experienced four or more
life stresses accounted for nearly one quarter of the cases of
depression. Among those with four or more life stresses who
developed depression, more than 40 percent had two copies of the
short gene compared to 17 percent with two copies of the long
version of the gene.
Researchers say more research is needed to confirm their findings.
This article was reported by Ivanhoe.com, who offers Medical Alerts
by e-mail every day of the week. To subscribe, go to:
http://www.ivanhoe.com/newsalert/.
SOURCE: Science, 2003;301:386-389
http://www.ivanhoe.com/channels/p_channelstory.cfm?storyid=6626

##########################################

Neuroscience researchers

Neuroscience researchers at Washington University School of
Medicine in St. Louis are studying the brains of patients with
Tourette Syndrome (TS) to see whether they can use sophisticated
imaging techniques to identify differences in the dopamine system of
people with the tics that characterize TS. A team of researchers,
led by Kevin J. Black, M.D., assistant professor of psychiatry,
neurology and radiology at Washington University School of Medicine,
is using PET imaging to see what the brain does in response to
levodopa, a natural amino acid that has been used for many years to
treat movement disorders, such as Parkinson's disease. With PET
imaging, the researchers can measure the boost in the brain's
dopamine levels in response to the drug both in people with Tourette
Syndrome and in those who do not have tics. By identifying
differences, they hope to isolate the causes of tics and to help
people with TS control or eliminate them.
http://news-info.wustl.edu/tips/page/normal/294.html

----------------------------------------------------------------
Note, If a link does not work, try cutting and pasting the entire
link into a new browser.
----------------------------------------------------------------
Credits
----------------------------------------------------------------

Paul Marshall PhD***
Tourette – Updates Moderator
http://groups.yahoo.com/group/Tourette-Updates

To receive these updates in your personal mail box send a blank e-
mail to:
Tourette-Updates-subscribe@yahoogroups.com

Comments or Questions:
Paul@t...

For more information on Tourette Syndrome you may visit my site at:
http://paul.tourette.info we are always adding and updating files.

***Permission is granted for posting this message in other groups
and
forums when including everything from the credits lines in your post
for our service at Tourette – Updates.

----------------------------------------------------------------
End
----------------------------------------------------------------