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Pathophysiological Modeling of Obsessive-Compulsive Disorder: Challenges, and Progress

  • Christopher Pittenger
    Correspondence
    Address correspondence to Christopher Pittenger, M.D., Ph.D., Director, Yale OCD Research Clinic, Assistant Professor of Psychiatry, Yale University School of Medicine, 34 Park St, W315, New Haven, Connecticut 06519
    Affiliations
    Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut
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      Animal models of disease can enormously advance our understanding of pathophysiology and the development of new treatments. Insight into Parkinson's disease, for example, has been greatly advanced by the demonstration that recapitulating pathologic degeneration of substantia nigra dopaminergic neurons produces behavioral changes reminiscent of the disorder and by subsequent pathophysiologic and therapeutic investigations in this model (
      • Harvey B.K.
      • Richie C.T.
      • Hoffer B.J.
      • Airavaara M.
      Transgenic animal models of neurodegeneration based on human genetic studies.
      ). Genetic models of Alzheimer's and Huntington's diseases have likewise been enormously fruitful in shining light on the pathophysiology of these conditions and identifying new therapeutic targets (
      • Harvey B.K.
      • Richie C.T.
      • Hoffer B.J.
      • Airavaara M.
      Transgenic animal models of neurodegeneration based on human genetic studies.
      ). Modeling of most psychiatric conditions has proven much more difficult, which has retarded the development of novel, pathophysiologically informed therapeutics (
      • Nestler E.J.
      • Hyman S.E.
      Animal models of neuropsychiatric disorders.
      ). The challenges to this project can be conceptualized in terms of the three ways that such models are traditionally evaluated.
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