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Evidence for Global Reduction in Brain Cyclic Adenosine Monophosphate Signaling in Depression

  • James M. O'Donnell
    Correspondence
    Address correspondence to James M. O'Donnell, Ph.D., Department of Behavioral Medicine and Psychiatry, School of Medicine, West Virginia University, Morgantown, West Virginia 25606
    Affiliations
    Department of Behavioral Medicine and Psychiatry, School of Medicine, West Virginia University, Morgantown, West Virginia
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  • Ying Xu
    Affiliations
    Department of Behavioral Medicine and Psychiatry, School of Medicine, West Virginia University, Morgantown, West Virginia
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      Fujita and coworkers, utilizing 11C-(R)-rolipram positron emission tomography, demonstrate that human subjects with major depression exhibit reductions in the enzyme phosphodiesterase-4 (PDE4) in a number of brain regions (
      • Fujita M.
      • Hines C.S.
      • Zoghbi S.S.
      • Mallinger A.G.
      • Dickstein L.P.
      • Liow J.-S.
      • et al.
      Downregulation of brain phosphodiesterase type IV measured with11C-(R)-rolipram positron emission tomography in major depressive disorder.
      ). PDE4, a cyclic adenosine monophosphate (AMP) phosphodiesterase, is an important regulator of cyclic AMP concentrations in the brain; it has been suggested as a molecular target for antidepressant drug discovery (
      • O'Donnell J.M.
      • Zhang H.T.
      Antidepressant effects of inhibitors of cAMP phosphodiesterase (PDE4).
      ). The present study provides support for this premise and also suggests that global reductions in cyclic AMP signaling in the brain may be associated with major depression.
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