Metabolic Syndrome and HPA Axis Biomarkers for Major Depressive Disorder

Abstract

Materials and methods for using combinations of metabolic syndrome and HPA axis biomarkers for monitoring major depressive disorder.

What is claimed is: 
     
         1 . A method for determining whether a human subject has depression, comprising
 (a) providing numerical values for a plurality of parameters predetermined to be relevant to depression, wherein the plurality of parameters comprises one or more hypothalamic-pituitary-adrenal (HPA) axis markers and one or more metabolic markers;   (b) individually weighting each of the numerical values by a predetermined function, each function being specific to each parameter;   (c) determining the sum of the weighted values;   (d) determining the difference between the sum and a control value; and   (e) if the difference is greater than a predetermined threshold, classifying the individual as having depression, or, if the difference is not greater than the predetermined threshold, classifying the individual as not having depression.   
     
     
         2 . The method of  claim 1 , wherein the depression is associated with major depressive disorder (MDD). 
     
     
         3 . The method of  claim 2 , wherein an algorithm is used to calculate an MDD score that can be used to support the diagnosis of MDD. 
     
     
         4 . The method of  claim 1 , wherein the HPA axis markers are selected from the group consisting adrenocorticotropic hormone, cortisol, epidermal growth factor, granulocyte colony stimulating factor, pancreatic polypeptide, vasopressin, and corticotrophin releasing hormone, and the metabolic markers are selected from the group consisting of acylation stimulating protein, adiponectin, apolipoprotein CIII, C-reactive protein, fatty acid binding protein, prolactin, resistin, insulin, testosterone, and thyroid stimulating hormone. 
     
     
         5 . The method of  claim 1 , wherein the plurality of parameters comprises clinical measurements relevant to metabolic syndrome. 
     
     
         6 . The method of  claim 5 , wherein the clinical measurements are selected from the group consisting of body mass index, fasting glucose levels, blood pressure, central obesity, high density lipoprotein, and triglycerides. 
     
     
         7 . The method of  claim 1 , wherein the plurality of parameters comprises the level of one or more catecholamines or catecholamine metabolites in urine. 
     
     
         8 . The method of  claim 1 , wherein the plurality of parameters comprises one or more inflammatory biomarkers. 
     
     
         9 . The method of  claim 1 , wherein the plurality of parameters comprises one or more neurotrophic biomarkers. 
     
     
         10 . A method for monitoring treatment of an individual diagnosed with a depression disorder, comprising:
 (a) using an algorithm to determine a first MDD disease score based on the levels of a plurality of analytes in a biological sample from the individual, wherein the plurality of analytes comprise one or more HPA axis biomarkers and one or more metabolic biomarkers;   (b) using the algorithm to determine a second MDD disease score after treatment of the individual for the depression disorder;   (c) comparing the score in step (a) to the score in step (b) and to a control MDD disease score, and classifying the treatment as being effective if the score in step (b) is closer than the score in step (a) to the control MDD score, or classifying the treatment as not being effective if the score in step (b) is not closer than the score in step (a) to the control MDD score.   
     
     
         11 . The method of  claim 10 , wherein the second MDD disease score is determined weeks or months after treatment. 
     
     
         12 . The method of  claim 10 , wherein steps (b) and (c) are repeated over time to monitor the individual's response to treatment, the change in the individual's MDD status, or the progression of MDD in the individual. 
     
     
         13 . The method of  claim 10 , wherein a subset of the plurality of analytes are measured at time points prior to and after the initiation of treatment. 
     
     
         14 . The method of  claim 10 , further comprising including in the algorithm parameters comprising clinical measurements relevant to metabolic syndrome. 
     
     
         15 . The method of  claim 14 , wherein the clinical measurements are selected from the group consisting of body mass index, fasting glucose levels, blood pressure, central obesity, high density lipoprotein, and triglycerides. 
     
     
         16 . The method of  claim 10 , wherein the biological sample is serum. 
     
     
         17 . The method of  claim 10 , wherein the biological sample is plasma. 
     
     
         18 . The method of  claim 10 , wherein the biological sample is cerebrospinal fluid. 
     
     
         19 . The method of  claim 10 , wherein the biomarkers are nucleic acids and the biological sample is comprised of cells or tissue. 
     
     
         20 . The method of  claim 10 , wherein the plurality of analytes comprises the level of one or more catecholamines or catecholamine metabolites in urine. 
     
     
         21 . The method of  claim 10 , wherein the one or more metabolic biomarkers comprise one or more thyroid hormones. 
     
     
         22 . The method of  claim 10 , wherein the one or more metabolic biomarkers comprise testosterone. 
     
     
         23 . The method of  claim 10 , wherein the plurality of analytes comprises one or more inflammatory biomarkers. 
     
     
         24 . The method of  claim 10 , wherein the plurality of analytes comprises one or more neurotrophic biomarkers. 
     
     
         25 . The method of  claim 10 , further comprising adjusting the treatment of the individual if the score in step (b) is not closer than the score in step (a) to the control MDD score. 
     
     
         26 . The method of  claim 10 , wherein the control MDD score is an MDD score calculated for a normal individual or the average of MDD scores calculated for a plurality of normal individuals. 
     
     
         27 . A method for determining whether an individual is likely to have depression, comprising
 (a) providing a biological sample from the individual;   (b) measuring the level of an analyte in the biological sample, wherein the analyte is selected from the group consisting of apolipoprotein CIII, epidermal growth factor, prolactin, and resistin;   (c) comparing the measured level with a control level of the analyte; and   (d) if the level of the analyte is greater than the control level, classifying the individual as likely to have depression, or if the level of the analyte is not greater than the control level, classifying the individual as not likely to have depression.   
     
     
         28 . The method of  claim 27 , wherein the biological sample is a serum sample. 
     
     
         29 . The method of  claim 27 , wherein the depression is associated with MDD.