Methods and Compositions for Treatment and Prevention of Major Depressive Disorder

Abstract

The present invention relates to methods of diagnosing, prognosing or treating diseases or disorders in which elevated levels of Abeta protein, including abeta 1-42 are prevalent. In particular, the present invention relates to methods of diagnosing, prognosing or treating a major or minor depressive episode/disorder attributed to elevated levels of Abeta protein, including abeta 1-42 , found particularly in body fluids including whole blood, blood cells, serum, plasma, urine and CSF. The invention also relates to the treatment of these disorders by administering an agent that either prevents production of Abeta, prevents aggregation of Abeta fibrils, or that increases the degradation or clearance of Abeta. In addition, the invention provides a method of treating or preventing a major or minor depressive disorder comprising administering an agent that prevents or interferes with Abeta-induced neurotoxicity. The present invention also relates to pharmaceutical compositions comprising such agents and methods of screening for novel agents.

1 . A method of screening, diagnosis or prognosis of a major or minor depressive episode/disorder in a subject, or for identifying a subject at risk for developing a major or minor depressive episode/disorder, or for monitoring the effect of therapy administered to a subject having a major or minor depressive episode/disorder, said method comprising:
 a) collecting a biological test sample from said subject;   b) analyzing said test sample for the presence of amyloid beta levels; and   c) comparing the level of amyloid beta in the test sample with the level of amyloid beta in one or more persons free from a major or minor depressive episode/disorder, or with a previously determined reference range for amyloid beta established from subjects free of a major or minor depressive disorder.   
     
     
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         3 . The method of  claim 1 , wherein the elevation of amyloid beta in a subject correlates with the presence of a major or minor depressive episode/disorder. 
     
     
         4 . The method of  claim 3 , wherein said amyloid beta is Aβ 40  or Aβ 42  and wherein said elevation of amyloid β is the result of an increase in production or generation of Aβ 40  or Aβ 42  as determined by measurement of Aβ 40  or Aβ 42  in a 24 hour urine sample. 
     
     
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         23 . A pharmaceutical composition for the treatment of a major depressive disorder comprising an agent that reduces the level of amyloid beta and a pharmaceutically acceptable carrier. 
     
     
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         28 . A method of identifying a subject at risk for developing a major or minor depressive episode/disorder, said method comprising:
 a. collecting a test sample from said subject;   b. analyzing said test sample for the presence of amyloid beta levels; and   c. comparing the level of amyloid beta in the test sample with the level of amyloid beta in one or more persons free from a major or minor depressive episode/disorder, or with a previously determined reference range for amyloid beta established from subjects free of a major or minor depressive disorder.   
     
     
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