Body Clock May Affect Bipolar Mania
Glitch in a Circadian Rhythm Gene Tied to Mania in Mice
WebMD News Archive
March 19, 2007 -- Mania in bipolar illness may be tied to a mutation in a
"body clock" gene, a new study shows.
Bipolar disorder, formerly called manic depression, is marked by two starkly
different phases -- the manic phase and the depressive phase.
Symptoms of the manic phase may include unusually high energy, less need for
sleep, excessive talk, racing thoughts, euphoria, irritability, inflated
self-esteem, hallucinations, and delusions.
Symptoms of the depressive phase may include depression, low self-esteem,
low energy levels, sadness, loneliness, helplessness, guilt, slow speech,
fatigue, poor coordination, insomnia, oversleeping, suicidal thoughts and
feelings, poor concentration, and lack of pleasure or interest in usual
The new study only included mice, not people. But the mouse model of mania
shows a "striking" similarity to some human manic behaviors, note the
They included Colleen McClung, PhD, assistant professor of psychiatry at the
University of Texas Southwestern Medical Center in Dallas.
Circadian Rhythm Gene
McClung's team studied the CLOCK gene in mice. The CLOCK gene is involved in
circadian rhythms (the so-called "body clock"), which affect sleep,
activity, hormones, and appetite.
The researchers studied some mice with a CLOCK gene mutation. For
comparison, they also studied mice with normal CLOCK genes.
In a series of lab tests, the mice with the CLOCK gene mutation displayed
manic behavior. Those mice were hyperactive, less anxious, and less depressed
than mice without the CLOCK gene mutation.
For instance, the mice with the mutation were less fearful than other mice
when they were put in a wide open space.
The mice with the CLOCK gene mutation also slept less and showed a greater
brain response to sugary water, cocaine, and mild electrical stimulation to the
Responsive to Lithium
Lastly, the researchers added lithium, a drug used to treat bipolar
disorder, to the drinking water of the mice with the CLOCK gene mutation.
After drinking the lithium-laced water, the mice with the CLOCK gene
mutation shed their manic behavior and began acting like mice without the CLOCK
The mice's mania with the CLOCK gene mutation was "strikingly similar in
several behavioral dimensions to bipolar patients when in the manic state,
including their treatment by lithium," write McClung and colleagues.
The CLOCK gene may help regulate mood, note the researchers.
"Our analysis of CLOCK's role in these behaviors is just beginning,"
write McClung and colleagues.
Their findings appear in the early online edition of Proceedings of the
National Academy of Sciences.