[Adta] Fw: COMMON GENE VERSION OPTIMIZES THINKING -- BUT WITH A
POSSIBLE DOWNSIDE
Barbara A Busse
busse002 at mc.duke.edu
Mon Feb 12 10:46:52 EST 2007
Thought this was very interesting. Barbara Busse
----- Forwarded by Barbara A Busse/MCLibrary/mc/Duke on 02/12/2007 10:45 AM
-----
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THINKING -- BUT WITH A POSSIBLE
DOWNSIDE
02/09/2007 09:24
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U.S. Department of Health and Human Services
NATIONAL INSTITUTES OF HEALTH
NIH News
National Institute of Mental Health (NIMH)
<http://www.nimh.nih.gov/>
EMBARGOED FOR RELEASE: Thursday, February 8, 2007, 5:00 p.m. ET
CONTACT: Jules Asher, NIMH press office, 301-443-4356, <e-mail:
NIMHpress at nih.gov>
COMMON GENE VERSION OPTIMIZES THINKING -- BUT WITH A POSSIBLE DOWNSIDE
Most people inherit a version of a gene that optimizes their brain's
thinking circuitry, yet also appears to increase risk for schizophrenia*, a
severe mental illness marked by impaired thinking, scientists at the
National Institutes of Health's (NIH) National Institute of Mental Health
(NIMH) have discovered. The seeming paradox emerged from the first study
to explore the effects of variation in the human gene for a brain master
switch, DARPP-32.
The researchers identified a common version of the gene and showed how it
impacts the way two key brain regions exchange information, affecting a
range of functions from general intelligence to attention.
Three fourths of subjects studied had at least one copy of the version that
results in more efficient filtering of information processed by the brain's
executive hub, the prefrontal cortex. However, the same version was also
more prevalent among people who developed schizophrenia, a severe mental
illness marked by delusions, hallucinations and impaired emotion that
affects one percent of the population.
"We have found that DARPP-32 shapes and controls a circuit coursing between
the human striatum and prefrontal cortex that affects key brain functions
implicated in schizophrenia, such as motivation, working memory and reward
related learning," explained Andreas Meyer-Lindenberg, M.D.
"Our results raise the question of whether a gene variant favored by
evolution, that would normally confer advantage, may translate into a
disadvantage if the prefrontal cortex is impaired, as in schizophrenia,"
added Daniel Weinberger, M.D. "Normally, enhanced cortex connectivity with
the striatum would provide increased flexibility, working memory capacity
and executive control. But if other genes and environmental events conspire
to render the cortex incapable of handling such information, it could
backfire -- resulting in the neural equivalent of a superhighway to a
dead-end."
Meyer-Lindenberg, Weinberger and colleagues in the NIMH Genes, Cognition
and Psychosis program report their results in the February 9, 2007 issue of
the "Journal of Clinical Investigation".
Previous studies in animals over two decades, most notably by Nobel
Laureate and NIMH grantee Paul Greengard, M.D., Rockefeller University, had
established that DARPP-32 in the striatum switches streams of information
from multiple brain chemical systems for processing by the cortex. Both the
neurotransmitter that it works through, dopamine, and the chromosomal site
of its gene have been implicated in schizophrenia.
"Although several groups have looked for possible clinical relevance of
DARPP-32, they have not met with great success," noted Greengard. "This
study shows a strong connection between this molecule and human cognition
-- and perhaps with schizophrenia."
"These first glimpses of DARPP-32 at work in the living human brain build
on a quarter century of investigations by Greengard's team that ultimately
linked this pivotal protein to depression and substance abuse as well as to
schizophrenia," added NIMH Director Thomas Insel, M.D.
To understand DARPP-32's role in the human brain, the NIMH researchers used
genetic, structural and functional magnetic resonance imaging, and
post-mortem techniques to identify the human gene's variants and their
functional consequences. Seventy five percent of subjects had the most
common version of the gene, which boosted circuit activation, structural
and functional connectivity and performance on thinking tasks, likely by
increasing gene expression. In 257 affected families, people with
schizophrenia were more likely to have this common version of the DARPP-32
gene.
Also participating in the study were: Richard Straub, Barbara Lipska, Beth
Verschinski, Terry Goldberg, Joseph Callicott, Michael Egan, Stephen
Huffaker, Venkata Mattay, Bhaskar Kolachana, Joel Kleinman, NIMH.
The National Institute of Mental Health (NIMH) mission is to reduce the
burden of mental and behavioral disorders through research on mind, brain,
and behavior. More information is available at the NIMH website <
http://www.nimh.nih.gov>.
The National Institutes of Health (NIH) -- The Nation's Medical Research
Agency -- includes 27 Institutes and Centers and is a component of the U.S.
Department of Health and Human Services. It is the primary federal agency
for conducting and supporting basic, clinical and translational medical
research, and it investigates the causes, treatments, and cures for both
common and rare diseases. For more information about NIH and its programs,
visit <www.nih.gov>.
---------------------------
*Schizophrenia information: <
http://www.nimh.nih.gov/healthinformation/schizophreniamenu.cfm>.
"Meyer-Lindenberg A, Straub R, Lipska B, Verchinski, B Goldberg T,
Callicott J, Egan M, Huffaker S, Mattay V, Kolachana B, Kleinman J,
Weinberger D. Genetic evidence implicating DARPP-32 in human
fronto-striatal structure, function and cognition. J.clin.investigation,
2/8/2007".
----------------------------
###
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<http://www.nih.gov/news/pr/feb2007/nimh-08.htm>.
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