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From: Tim on 20 Mar 2007 05:07
Gene controlling circadian rhythms may be involved in onset of bipolar
disorder

Bipolar Disorder :: Gene controlling circadian rhythms may be involved
in onset of bipolar disorder
Disrupt the gene that regulates the biological clocks in mice and they
become manic, exhibiting behaviors similar to humans with bipolar
disorder, UT Southwestern Medical Center researchers have found.

In a study available online in the Proceedings of the National Academy
of Sciences, scientists from UT Southwestern show that the Clock gene,
which controls the body's circadian rhythms, may be integrally involved
in the development of bipolar disorder. Circadian rhythms include the
daily ups-and-downs of waking, eating and other processes such as body
temperature, hormone levels, blood pressure and heart activity.

"There's evidence suggesting that circadian genes may be involved in
bipolar disorder," said Dr. Colleen McClung, assistant professor of
psychiatry and the study's senior author. "What we've done is taken
earlier findings a step further by engineering a mutant mouse model
displaying an overall profile that is strikingly similar to human mania,
which will give us the opportunity to study why people develop mania or
bipolar disorder and how they can be treated."

Bipolar disorder, also known as manic-depressive illness, is a brain
disorder that causes dramatic shifts in a person's mood, energy and
ability to function � much more severe than the normal ups and downs
that most people experience. About 5.7 million American adults, or about
2.6 percent of the adult population, suffer from the psychiatric disorder.

The study included putting the mutant mice through a series of tests,
during which they displayed hyperactivity, decreased sleep, decreased
anxiety levels, a greater willingness to engage in "risky" activities,
lower levels of depression-like behavior and increased sensitivity to
the rewarding effects of substances such as cocaine and sugar.

"These behaviors correlate with the sense of euphoria and mania that
bipolar patients experience," said Dr. McClung. "In addition, there is a
very high co-morbidity between drug usage and bipolar disorder,
especially when patients are in the manic state."

During the study, lithium was given to the mutant mice. Lithium, a
mood-stabilizing medication, is most commonly used in humans to treat
bipolar patients. Once treated with the drug on a regular basis, the
majority of the study's mice reverted back to normal behavioral
patterns, as do humans.

The researchers also injected a functional Clock gene protein �
basically giving the mice their Clock gene back � into a specific region
of the brain that controls reward functions and where dopamine cells are
located. Dopamine is a neurotransmitter associated with the "pleasure
system" of the brain and is released by naturally rewarding experiences
such as food, sex and the use of certain drugs. This also resulted in
the mice going back to normal behaviors.

"While the Clock gene is expressed throughout the brain, it's really
only been studied in one particular brain region, which is the one
that's involved in circadian rhythms," said Dr. McClung. "This is one of
the first studies to show that Clock has a major effect on behavior in a
different brain region � specifically the one that controls reward
responses and mood."

Dr. Eric Nestler, chairman of UT Southwestern's psychiatry department
and also a study author, said the research is important because it
establishes the first complete mouse model for studying bipolar disorder.

"The lack of an animal model for bipolar disorder has been a crucial
limitation in our efforts to better understand the biological basis of
the disorder," said Dr. Nestler, who holds the Lou and Ellen McGinley
Distinguished Chair in Psychiatric Research. "Dr. McClung's findings are
therefore very important for the field and provide fundamentally new
directions for one day developing improved treatments."

(Last updated on Monday, March 19, 2007, and first posted on Monday,
March 19, 2007)

http://www.webmd.com/bipolar-disorder/news/20070319/body-clock-may-affect-bipolar-mania
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