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    Body Clock May Affect Bipolar Mania

    Glitch in a Circadian Rhythm Gene Tied to Mania in Mice
    WebMD Health News
    Reviewed by Louise Chang, MD

    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 activities.

    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 researchers.

    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 brain.

    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 gene mutation.

    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.

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