Treatment of mood and stress related disorders

Abstract

A pharmaceutical composition and method for treating or attenuating a mood or stress-related disorder in a subject having normal or low inflammatory state is provided. In some embodiments, the pharmaceutical composition and method of the invention comprise activating or stimulating microglia for treatment of mood or stress-related disorder.

1 . A method for treating or attenuating a disease or disorder in a subject in need thereof, the method comprising the steps of:
 a. determining the inflammatory state of said subject, wherein normal or low inflammatory state of said subject is indicative that said subject is suitable for treatment by microglia stimulator therapy, and   b. treating a subject determined as being suitable for microglia stimulator therapy with a therapeutically effective amount of a microglia stimulator, thereby treating or attenuating a disease or disorder in the subject.   
     
     
         2 . The method of  claim 1 , wherein the subject is afflicted with a microglia-associated disease or disorder. 
     
     
         3 . The method of  claim 1 , wherein the disease or disorder is a mood or stress-related disorder. 
     
     
         4 . The method of  claim 3 , wherein said stress-related disorder is selected from the group consisting of: posttraumatic stress disorder, acute stress disorder, adjustment disorder, bereavement related disorder, general anxiety disorder, social anxiety disorder, and anxiety disorder due to a medical condition. 
     
     
         5 . The method of  claim 3 , wherein said mood disorder is selected from the group consisting of: major depressive disorder, unipolar major depressive episode, dysthymic disorder, treatment-resistant depression, bipolar depression, adjustment disorder with depressed mood, cyclothymic disorder, atypical depression, seasonal affective disorder, melancholic depression, psychotic depression, post-schizophrenic depression, depression due to a general medical condition, post-viral fatigue syndrome, and chronic fatigue syndrome. 
     
     
         6 . The method of  claim 1 , wherein the disease or disorder is a neurodegenerative disease. 
     
     
         7 . The method of  claim 1 , wherein said normal or low inflammatory state is detected by determining the level of at least one inflammatory marker. 
     
     
         8 . The method of  claim 7 , wherein said at least one inflammatory marker is selected from C-reactive protein (CRP), interleukin 6 (IL-6) and tumor necrosis factor alpha (TNFα), wherein a level of any one of: (i) less than 3 mg/L CRP, (ii) less than 2.0 pg/ml IL-6, (iii) less than 3.8 pg/ml TNFα, and (iv) any combination of (i) to (iii). 
     
     
         9 . The method of  claim 1 , wherein said normal or low inflammatory state is plasma CRP levels lower than 3 mg/L. 
     
     
         10 . The method of  claim 1 , wherein said normal or low inflammatory state is Erythrocyte Sedimentation Rate (ESR) of less than 6.3 mm/h. 
     
     
         11 . The method of  claim 1 , wherein said normal or low inflammatory state is detected by determining the level of activated microglia. 
     
     
         12 . The method of  claim 1 , wherein said inflammatory state is assessed by positron emission tomography (PET) imaging. 
     
     
         13 . The method of  claim 1 , wherein said normal or low inflammatory state is an increase in dystrophic microglia. 
     
     
         14 . The method of  claim 1 , wherein said microglia stimulator is a colony stimulating factor 1 receptor ligand (CSF1R). 
     
     
         15 . The method of  claim 14 , wherein said CSF1R is selected from the group consisting of: macrophage colony-stimulating factor (M-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and Interleukin 34 (IL-34).