Commentary| Volume 62, ISSUE 1, P4-6, July 01, 2007

In Search of the Holy Grail for the Treatment of Neurodegenerative Disorders: Has a Simple Cation Been Overlooked?

  • De-Maw Chuang
    Address reprint requests to De-Maw Chuang, Ph.D., Molecular Neurobiology Section, Mood and Anxiety Disorders Program, National Institute of Mental Health, National Institutes of Health, Building 10, Room 4C-206, 10 Center Drive MSC 1363, Bethesda, MD 20892-1363
    Mood and Anxiety Disorders Program, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland.
    Search for articles by this author
  • Husseini K. Manji
    Mood and Anxiety Disorders Program, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland.
    Search for articles by this author
      In recent years, there has been considerable excitement about the possibility that the “molecular medicine revolution” would lead to identification of numerous putative targets designed to slow the atrophic/degenerative process in various neuropsychiatric disorders. Indeed, tremendous progress has been made in the identification of cellular processes and pathways involved in numerous degenerative diseases; however, to date, proliferation of candidate drugs has not resulted in viable novel clinical treatments for these devastating disorders (
      • Heemskerk J.
      • Tobin A.J.
      • Ravina B.
      From chemical to drug: Neurodegeneration drug screening and the ethics of clinical trials.
      ). Ironically, the article by Bearden et al. (pages 7–16, in this issue) of the journal suggests that an old medication present in our therapeutic armamentarium for half a century exerts neurotrophic effects not only in animal models but also in humans. Bearden et al. used high-resolution magnetic resonance imaging and cortical pattern matching methods to map gray matter differences in 28 bipolar patients, 20 lithium-treated, and 28 healthy control subjects. Their results showed gray matter density was significantly greater in bipolar patients compared with healthy subjects in diffuse cortical regions, notably bilateral cingulated and paralimbic cortices, areas utilized in attention, motivation, and emotion. Additionally, their data revealed greater gray matter density in the right anterior cingulate in lithium-treated patients relative to the bipolar subjects not taking lithium. Their lithium-treated sample included subjects who were on lithium for varying time durations at different individual doses. The lack of difference in gray mater density between the untreated patients and healthy control subjects, as well as growing evidence that lithium exerts major effects on a number of cellular proteins and pathways (vide infra) known to regulate cell atrophy/death, lend support to the view that gray matter enlargement is mediated through the trophic actions of lithium in the brain.
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