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Thread: Lithium Builds Gray Matter in Bipolar Brains, UCLA Study Shows

  1. #1

    Lithium Builds Gray Matter in Bipolar Brains, UCLA Study Shows

    Well this obviously supports the lithium SCI trials that are to begin with ChinaSCINet. I wonder if any other MRI based growth comparisons were made in this study, such as the spinal cord or any other part of the neurological system? Would be interesting to see how ingesting lithium could possibly affect only one area of the nervous system, but not others...


    Christopher



    http://www.newsroom.ucla.edu/page.asp?RelNum=7842

    Date: April 6, 2007
    Contact: Mark Wheeler ( mwheeler@mednet.ucla.edu )
    Phone: 310-794-2265

    Lithium Builds Gray Matter in Bipolar Brains, UCLA Study Shows


    Neuroscientists at UCLA have shown that lithium, long the standard treatment for bipolar disorder, increases the amount of gray matter in the brains of patients with the illness.

    The research is featured in the July issue of the journal Biological Psychiatry and is currently available online.

    Carrie Bearden, a clinical neuropsychologist and assistant professor of psychiatry at UCLA, and Paul Thompson, associate professor of neurology at the UCLA Laboratory of NeuroImaging, used a novel method of three-dimensional magnetic resonance imaging (MRI) to map the entire surface of the brain in people diagnosed with bipolar disorder.

    When the researchers compared the brains of bipolar patients on lithium with those of people without the disorder and those of bipolar patients not on lithium, they found that the volume of gray matter in the brains of those on lithium was as much as 15 percent higher in areas that are critical for attention and controlling emotions.

    The neurobiological underpinnings of bipolar disorder — an illness marked by a roller coaster of emotions between mania and depression — are not well understood. Nor is it understood how lithium works in controlling these severe mood swings, even though it has been the standard treatment for some 50 years. These new findings suggest that lithium may work by increasing the amount of gray matter in particular brain areas, which in turn suggests that existing gray matter in these regions of bipolar brains may be underused or dysfunctional.

    This is the first time researchers were able to look at specific regions of the brain that may be affected by lithium treatment in living human subjects, said Bearden.

    "We used a novel method for brain imaging analysis that is exquisitely sensitive to subtle differences in brain structure," she said. "This type of imaging has not been used before to study bipolar patients. We also revealed how commonly used medications affect the bipolar brain."

    Although other studies have measured increases in the overall volume of the brain, Bearden said, this imaging method allowed the researchers to see exactly which brain regions were affected by lithium.

    "Bipolar patients who were taking lithium had a striking increase in gray matter in the cingulate and paralimbic regions of the brain," she said. "These regions regulate attention, motivation and emotion, which are profoundly affected in bipolar illness."

    While conventional MRI studies have measured brain volume in total, this new image analysis allows researchers to examine differences in cortical anatomy at a much greater spatial resolution.

    In this study, Bearden and colleagues at UCLA used computer analysis to analyze brain scans collected by collaborators at the University of Pittsburgh in order to determine whether bipolar patients showed changes in brain tissue and, if so, whether those changes were influenced by lithium treatment. Specifically, they employed high-resolution MRI and cortical pattern-matching methods to map gray matter differences in 28 adults with bipolar disorder — 70 percent of whom were lithium-treated — and 28 healthy control subjects. Detailed spatial analyses of gray matter distribution were conducted by measuring local volumes of gray matter at thousands of locations in the brain.

    While the brains of lithium-treated bipolar patients did not differ from those of the control subjects in total white-matter volume, their overall gray-matter volume was significantly higher, sometimes by as much as 15 percent.

    Unfortunately, said Bearden, there is no evidence that the increase in gray matter persists if lithium treatment is discontinued. "But it does suggest that lithium can have dramatic effects on gray matter in the brain," she said. "This may be an important clue as to how and why it works."

    Other authors in the study included Manish Dalwani, Kiralee M. Hayashi, Agatha D. Lee, Mark Nicoletti, Michael Trakhtenbroit, David C. Glahn, Paolo Brambilla, Roberto B. Sassi, Alan G. Mallinger, Ellen Frank, David J. Kupfer, and Jair C. Soares.

    Graphics from the study are available online at: http://www.loni.ucla.edu/~khayashi/T...10_bipolar.tif.

    The UCLA Department of Neurology encompasses more than a dozen research, clinical and teaching programs. These programs cover brain mapping and neuroimaging, movement disorders, Alzheimer's disease, multiple sclerosis, neurogenetics, nerve and muscle disorders, epilepsy, neuro-oncology, neurotology, neuropsychology, headaches and migraines, neurorehabilitation, and neurovascular disorders. The department ranked No. 1 among its peers nationwide in National Institutes of Health funding in 2005.

    For more information, visit http://neurology.medsch.ucla.edu.

  2. #2
    I saw this last night too. It would be interesting to know if lithium could rebuild gray matter in the injured spinal cord too which is where the neurons reside. If so, it would be a huge boost for the field of neuronal regeneration which is considered more challenging than axonal regeneration.

  3. #3
    Senior Member Norm's Avatar
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    I always felt the cure or something like it would happen by accident.
    "Some people say that, the longer you go the better it gets the more you get used to it, I'm actually finding the opposite is true."

    -Christopher Reeve on his Paralysis

  4. #4
    Quote Originally Posted by Norm
    I always felt the cure or something like it would happen by accident.
    Like Viagra.

    "Hmmm, maybe this will work for chest pain. Look at that, it makes
    people hard too".

  5. #5
    Lithium salts have been used to treat bipolar disorder as "mood stabilizing" drugs for about a hundred years. According to Wikipeda (Source), Carl Lange in Denmark and William Alexander Hammond in New York used lithium to treat mania from 1870's onward. But this was forgotten in the 1900's and rediscovered in 1949 by John Cade in 1949 who was studying the effects of lithium on animals. He found that lithium had a tranquilizing effect on animals and subsequently applied it to chronically hospitalized patients. Because lithium is toxic even with relatively small overdoses and some peple used lithium as a substitute for table salt, there was resistance to its use. It was not until 1970, through the efforts of Mogen Schou in Denmark and Samuel Gershon in the U.S., that the US FDA approved the drug for manic depression.

    Several aspects of lithium are well known. First, it often takes as long as a week for the drug to have an effect. Second, it can prevent depression and mania in bipolar disorder. Third, it may be useful in combination with other drugs. Fourth, although lithium was thought to be not useful for children, recent studies suggest that it is effective for early onset bipolar disorder in children. Fifth, although most authorities including Wikipedia say that the "precise mechanism of action of Li as a mood-stabilizing agent is currently unknown", this is not true and may be because the people who write reviews of lithium are psychiatrists who don't understand the molecular and cellular literature.

    Early theories of Li mechanisms suggested that lithium substitutes for Na and may interfere with the Na:K pump. By the way, the description in Wikipedia of how lithium may affect membrane potential, action potential, and the Na/K pump is wrong. The much more important mechanism of action is the discovery that lithium inhibits glycogen synthetase kinase 3-beta (GSK-3b) enzyme which phosphorylates many nuclear factors. Inhibition of GSK-3b prevents phosphorylation of the nuclear factors. Dephosphorylated nuclear factors enter into the nucleus and turn on genes. As it turns out, the nuclear factors that GSK-3b inhibits (beta catenin, NFAT) are ones that make neurons grow and results in cellular proliferation and neurotrophin production.

    The first report that Li may be useful for spinal cord injury comes from Yick, Wu, and So at Hong Kong University. They gave the lithium and chondroitinase to rats with hemisected spinal cords and showed that the two therapies together was more effective than either one alone in causing regeneration in the hemisected cord. There is a huge literature suggesting that lithium stimulates bone marrow stem cells. We showed that it stimulates cord blood cells to put out neurotrophins and that it does so to cord blood cells transplanted into the spinal cord. This is the reason why we are planning to test this therapy in the ChinaSCINet, as part of the combination therapy that will address the three major obstacles to regeneration.

    It is not surprising that lithium increases gray matter in the brain. It increases bone marrow that have been irradiated. We will be looking for increases in gray matter in the spinal cord in our trials.

    Wise.

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