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Depression and Adenylyl Cyclase: Sorting Out the Signals

      The article in this issue of Biological Psychiatry by Chen et al. (
      • Chen X.
      • Luo J.
      • Leng Y.
      • Yang Y.
      • Zweifel L.S.
      • Palmiter R.D.
      • Storm D.R.
      Ablation of type III adenylyl cyclase in mice causes reduced neuronal activity, altered sleep pattern, and depression-like phenotypes.
      ) suggests that knockout of adenylyl cyclase 3 (AC3—Adcy3) leads to depression. The study knocks out AC3 three ways: globally, targeted to forebrain, or conditionally. In a comprehensive series of behavioral studies, the data from this study reveal a “depressive” phenotype. This thorough and thoughtful study was undertaken, at least in part, pursuant to the suggestion that ADCY3 polymorphisms track with major depressive disorder (MDD). Consideration of this work, along with other mouse and human data, raises the question: What is our current knowledge of cyclic adenosine monophosphate (cAMP) and adenylyl cyclase in MDD?
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