Biomarkers

Abstract

The invention relates to a method of differentially diagnosing schizophrenia, bipolar disorder and major depressive disorder.

1 - 19 . (canceled) 
     
     
         20 . A method of differential diagnosis for schizophrenia, bipolar disorder, or major depressive disorder or a predisposition thereto in an individual, comprising:
 a) obtaining a biological sample of an individual;   b) quantifying concentrations of a panel of biomarkers in the biological sample;   c) generating a biomarker profile from the concentrations of the panel of biomarkers of the individual;   d) determining that the biomarker profile of the individual has a statistically significant similarity with either one of a biomarker profile obtained from healthy control subjects, subjects with schizophrenia, subjects with bipolar disorder, or subjects with major depressive disorder; and   e) classifying the individual as healthy or as suffering from or having a predisposition for either schizophrenia or bipolar disorder or major depressive disorder based at least in part on the statistically significant similarity of the biomarker profile of the individual to the biomarker profile of healthy control subjects or subjects with either schizophrenia, bipolar disorder or major depressive disorder;   wherein the panel of biomarkers comprises one or more analytes selected from Creatine Kinase MB, S100b, or IL-1ra.   
     
     
         21 . The method of  claim 20 , wherein the panel of biomarkers further comprises one or more analytes selected from Apolipoprotein H, AXL, BDNF (Brain Derived Neurotrophic Factor), Betacellulin, Complement 3, CgA (Chromogranin A), EGF R, Endothelin 1, Fas, FGF basic, Haptoglobin, HGF (Hepatocyte growth factor), Ig A, IL 12p70, IL 10, IL 13, IL 16, IL 1beta, IL 2, Lipoprotein a, MDC, MMP 3, PAI 1, PDGF, Prolactin, Peptide YY, Serum Amyloid P, Thyroxine Binding Globulin, Testosterone, Thyroid Stimulating Hormone, TSP 1, or von Willebrand Factor. 
     
     
         22 . The method of  claim 21 , wherein the panel of biomarkers further comprises one or more analytes selected from Alpha 1 Antitrypsin, ACTH (Adrenocorticotropic Hormone), AgRP (Agouti related Protein), Apolipoprotein A1, BLC (B Lymphocyte Chemoattractant), Cancer Antigen 125, Carcinoembryonic Antigen, Cortisol, CTGF (Connective Tissue Growth Factor), EN RAGE, Eotaxin, Epiregulin, Erythropoietin, Factor VII, Fas Ligand, Ferritin, Fibrinogen, FSH (Follicle Stimulating Hormone), GM CSF, GST, HB EGF, IFN gamma, IGF-1, Ig M, IL 15, IL 18, IL 1alpha, IL 3, IL 4, IL 5, IL 7, Leptin, LH (Luteinizing Hormone), Lymphotactin, M CSF, MIP 1 alpha, MIP 3 alpha, MIP 1 beta, Myoglobin, NrCAM, Prostatic Acid Phosphatase, PAPPA, Progesterone, Prostate Specific Antigen Free, PARC, RANTES, Resistin, SGOT, SHBG, SOD, sRAGE, Tamm-Horsfall Protein (THP), Tissue Factor, TECK, TIMP 1, TNF RII, TRAIL R3, or VCAM 1. 
     
     
         23 . The method of  claim 20 , wherein the biological sample comprises cerebrospinal fluid, whole blood, blood serum, plasma, urine, saliva, other bodily fluid, breath, condensed breath, or an extract, purification, or dilution of any of these. 
     
     
         24 . The method of  claim 20 , wherein quantifying comprises SELDI (-TOF) spectrometry, MALDI (-TOF) spectrometry, a 1-D gel-based analysis, a 2-D gel-based analysis, mass spectrometry (MS), liquid chromatography (LC), reverse phase liquid chromatography (RP-LC), size permeation chromatography, gel filtration chromatography, ion exchange chromatography, affinity chromatography, FPLC, HPLC, UPLC, other LC-based techniques, other LC-MS-based technique, or combinations thereof. 
     
     
         25 . The method of  claim 20 , wherein quantifying comprises an immunological method, a biosensor method, a microanalytical method, a microengineered method, a microseparation method, an immunochromatography method, or combinations thereof. 
     
     
         26 . The method of  claim 20 , wherein one or more of the biomarkers may be replaced by a molecule, or a measurable fragment of the molecule, found upstream or downstream of the biomarker in a biological pathway. 
     
     
         27 . A method of differential diagnosis for major depressive disorder, schizophrenia, or healthy condition in an individual, comprising:
 a) obtaining a biological sample of an individual;   b) quantifying concentrations of a panel of biomarkers in the biological sample;   c) generating a biomarker profile from the concentrations of the panel of biomarkers of the individual;   d) determining that the biomarker profile of the individual has a statistically significant similarity with either one of a biomarker profile obtained from healthy control subjects, subjects with schizophrenia, or subjects with major depressive disorder; and   e) classifying the individual as healthy or as suffering from or having a predisposition for either schizophrenia or major depressive disorder based at least in part on the statistically significant similarity of the biomarker profile of the individual to the biomarker profile of healthy control subjects or subjects with either schizophrenia or major depressive disorder;   wherein the panel of biomarkers comprises one or more analytes selected from progesterone, IL-10, BDNF (Brain Derived Neurotrophic Factor), Serum Amyloid P, sRAGE, Betacellulin, CgA (Chromogranin A), Creatine Kinase MB, IGF-1, MIP 3 alpha, S100b, MMP 3, IL-1ra, Tamm-Horsfall Protein (THP), or IL 18.   
     
     
         28 . The method of  claim 27 , wherein the biological sample comprises cerebrospinal fluid, whole blood, blood serum, plasma, urine, saliva, other bodily fluid, breath, condensed breath, or an extract, purification, or dilution of any of these. 
     
     
         29 . The method of  claim 27 , wherein quantifying comprises SELDI (-TOF) spectrometry, MALDI (-TOF) spectrometry, a 1-D gel-based analysis, a 2-D gel-based analysis, mass spectrometry (MS), liquid chromatography (LC), reverse phase liquid chromatography (RP-LC), size permeation chromatography, gel filtration chromatography, ion exchange chromatography, affinity chromatography, FPLC, HPLC, UPLC, other LC-based techniques, other LC-MS-based technique, or combinations thereof. 
     
     
         30 . The method of  claim 27 , wherein quantifying comprises an immunological method, a biosensor method, a microanalytical method, a microengineered method, a microseparation method, an immunochromatography method, or combinations thereof. 
     
     
         31 . The method of  claim 27 , wherein one or more of the biomarkers may be replaced by a molecule, or a measurable fragment of the molecule, found upstream or downstream of the biomarker in a biological pathway. 
     
     
         32 . A method of treating an individual suspected of suffering from schizophrenia, bipolar disorder, or major depressive disorder or a predisposition thereto, comprising:
 a) obtaining a biological sample of an individual;   b) quantifying concentrations of a panel of biomarkers in the biological sample;   c) generating a biomarker profile from the concentrations of the panel of biomarkers of the individual;   d) determining that the biomarker profile of the individual has a statistically significant similarity with either one of a biomarker profile obtained from healthy control subjects, subjects with schizophrenia, subjects with bipolar disorder, or subjects with major depressive disorder;   e) differentially diagnosing the individual as healthy or as suffering from or having a predisposition for either schizophrenia or bipolar disorder or major depressive disorder based at least in part on the statistically significant similarity of the biomarker profile of the individual to the biomarker profile of healthy control subjects or subjects with either schizophrenia, bipolar disorder or major depressive disorder;   f) customizing a treatment regimen for the individual based at least in part on the differential diagnosis; and   g) effectuating the treatment regimen;   wherein the panel of biomarkers comprises one or more analytes selected from Creatine Kinase MB, S100b, or IL-1ra.   
     
     
         33 . The method of  claim 32 , wherein the panel of biomarkers further comprises one or more analytes selected from Apolipoprotein H, AXL, BDNF (Brain Derived Neurotrophic Factor), Betacellulin, Complement 3, CgA (Chromogranin A), EGF R, Endothelin 1, Fas, FGF basic, Haptoglobin, HGF (Hepatocyte growth factor), Ig A, IL 12p70, IL 10, IL 13, IL 16, IL 1beta, IL 2, Lipoprotein a, MDC, MMP 3, PAI 1, PDGF, Prolactin, Peptide YY, Serum Amyloid P, Thyroxine Binding Globulin, Testosterone, Thyroid Stimulating Hormone, TSP 1, or von Willebrand Factor. 
     
     
         34 . The method of  claim 33 , wherein the panel of biomarkers further comprises one or more analytes selected from Alpha 1 Antitrypsin, ACTH (Adrenocorticotropic Hormone), AgRP (Agouti related Protein), Apolipoprotein A1, BLC (B Lymphocyte Chemoattractant), Cancer Antigen 125, Carcinoembryonic Antigen, Cortisol, CTGF (Connective Tissue Growth Factor), EN RAGE, Eotaxin, Epiregulin, Erythropoietin, Factor VII, Fas Ligand, Ferritin, Fibrinogen, FSH (Follicle Stimulating Hormone), GM CSF, GST, HB EGF, IFN gamma, IGF-1, Ig M, IL 15, IL 18, IL 1alpha, IL 3, IL 4, IL 5, IL 7, Leptin, LH (Luteinizing Hormone), Lymphotactin, M CSF, MIP 1 alpha, MIP 3 alpha, MIP 1 beta, Myoglobin, NrCAM, Prostatic Acid Phosphatase, PAPPA, Progesterone, Prostate Specific Antigen Free, PARC, RANTES, Resistin, SGOT, SHBG, SOD, sRAGE, Tamm-Horsfall Protein (THP), Tissue Factor, TECK, TIMP 1, TNF RII, TRAIL R3, or VCAM 1. 
     
     
         35 . The method of  claim 34 , wherein the treatment regimen is further customized based at least in part on whether there is a statistically significant similarity or difference between the individual's biomarker profiles generated on two or more occasions. 
     
     
         36 . The method of  claim 35 , wherein biomarker profiles from the individual are generated prior to commencement of the treatment regimen, and/or at an earlier stage of the treatment regimen. 
     
     
         37 . The method of  claim 35 , wherein biomarker profiles from the individual are generated at intervals throughout the individual's lifetime. 
     
     
         38 . The method of  claim 34 , wherein customizing the treatment regimen further comprises one or more selections of therapy selected from: type and/or dosing of medications, type and/or duration of psychotherapy, type and/or duration of counseling, type and/or duration of hospitalization, type and/or dosing of electroconvulsive therapy. 
     
     
         39 . A kit for differentially diagnosing a healthy condition, schizophrenia, bipolar disorder or major depressive disorder, or predisposition for a healthy condition, schizophrenia, bipolar disorder or major depressive disorder, comprising a biosensor capable of quantifying MMP 3, Alpha 1 Antitrypsin, ACTH (Adrenocorticotropic Hormone), AgRP (Agouti related Protein), Apolipoprotein A1, Apolipoprotein H, AXL, Betacellulin, BLC (B Lymphocyte Chemoattractant), BDNF (Brain Derived Neurotrophic Factor), Complement 3, Cancer Antigen 125, Carcinoembryonic Antigen, CgA (Chromogranin A), Creatine Kinase MB, Cortisol, CTGF (Connective Tissue Growth Factor), EGF R, Endothelin 1, EN RAGE, Eotaxin, Epiregulin, Erythropoietin, Factor VII, Fas, Fas Ligand, Ferritin, FGF basic, Fibrinogen, FSH (Follicle Stimulating Hormone), GM CSF, GST, Haptoglobin, HB EGF, HGF (Hepatocyte growth factor), IFN gamma, IGF-1, Ig A, Ig M, IL 10, IL 12p70, IL 13, IL 15, IL 16, IL 18, IL 1 alpha, IL 1beta, IL 1ra, IL 2, IL 3, IL 4, IL 5, IL 7, Leptin, LH (Luteinizing Hormone), Lipoprotein a, Lymphotactin, M CSF, MDC, MIP 1 alpha, MIP 3 alpha, MIP 1beta, Myoglobin, NrCAM, PAI 1, Prostatic Acid Phosphatase, PAPPA, PDGF, Progesterone, Prolactin, Prostate Specific Antigen Free, PARC, Peptide YY, RANTES, Resistin, S100b, Serum Amyloid P, SGOT, SHBG, SOD, sRAGE, Tamm-Horsfall Protein (THP), Thyroxine Binding Globulin, Testosterone, Tissue Factor, TECK, TIMP 1, TNF RII, TRAIL R3, Thyroid Stimulating Hormone, TSP 1, VCAM 1, and von Willebrand Factor.