Diagnostic method for diagnosing depression and monitoring therapy effectiveness

1. A method for measuring concentration of biomarkers comprising

measuring the concentration of at least two biomarkers in urine samples from an individual suspected of having a mood disorder,

wherein the at least two biomarkers are Herpes Virus Entry Mediator (HVEM)(TNFRSF14)(UniProtKB/Swiss-Prot accession Q92956.3) (urine) and thromboxane (urine) and,

further measuring the concentration of one or more biomarkers measured in urine or blood samples selected from the group consisting of aldosteron (urine), substance P (urine), endothelin (urine and/or serum), isoprostane (urine), cortisol (urine and/or serum), Leukotriene B4 (LTB4) (urine), calprotectin (urine and/or serum), cyclic guanosine monophosphate (cGMP) (urine), leptin (serum), thromboxane (serum), and tumor necrosis factor (TNF) alpha receptor 2 (serum), and

wherein the measured concentration of urine biomarkers is normalized to the concentration of creatinine in the urine.

2. The method of claim 1 , wherein the biomarkers comprises thromboxane (urine), HVEM (urine) and aldosteron (urine), and one or more biomarkers selected from the group consisting of substance P (urine), endothelin (urine and/or serum), isoprostane (urine), cortisol (urine and/or serum), Leukotriene B4 (LTB4) (urine), calprotectin (urine and/or serum), cyclic guanosine monophosphate (cGMP) (urine), leptin (serum), thromboxane (serum), and tumor necrosis factor (TNF) alpha receptor 2 (serum), and

wherein the measured concentration of urine biomarkers is normalized to the concentration of creatinine in the urine.

3. The method of claim 1 , wherein the biomarkers comprises thromboxane (urine), HVEM (urine), aldosteron (urine), and substance P (urine), and one or more biomarkers selected from the group consisting of endothelin (urine and/or serum), isoprostane (urine), cortisol (urine and/or serum), LTB4 (urine), calprotectin (urine and/or serum), cGMP (urine), leptin (serum), thromboxane (serum), and tumor necrosis factor (TNF) alpha receptor 2 (serum).

4. The method of claim 1 , wherein the biomarkers comprises thromboxane (urine), aldosteron (urine), substance P (urine), and HVEM (urine), and one or more biomarkers selected from the group consisting of endothelin (urine and/or serum), isoprostane (urine), cortisol (urine and/or serum), LTB4 (urine), calprotectin (urine and/or serum), cGMP (urine), leptin (serum), thromboxane (serum), and tumor necrosis factor (TNF) alpha receptor 2 (serum).

5. The method of claim 1 , wherein the biomarkers comprises thromboxane (urine), aldosteron (urine), substance P (urine), HVEM (urine), and endothelin (urine), and one or more biomarkers selected from the group consisting of endothelin (serum), isoprostane (urine), cortisol (urine and/or serum), LTB4 (urine), calprotectin (urine and/or serum), cGMP (urine), leptin (serum), thromboxane (serum), and tumor necrosis factor (TNF) alpha receptor 2 (serum).

6. The method of claim 1 , wherein the biomarkers comprises thromboxane (urine), aldosteron (urine), substance P (urine), HVEM (urine), endothelin (urine), and isoprostane (urine), and one or more biomarkers selected from the group consisting of endothelin (serum), cortisol (urine and/or serum), LTB4 (urine), calprotectin (urine and/or serum), cGMP (urine), leptin (serum), thromboxane (serum), and tumor necrosis factor (TNF) alpha receptor 2 (serum).

7. The method of claim 1 , wherein the biomarkers comprises thromboxane (urine), aldosterone (urine), substance P (urine), HVEM (urine), endothelin (urine), isoprostane (urine), and cortisol (urine), and one or more biomarkers selected from the group consisting of endothelin (serum), cortisol (serum), LTB4 (urine), calprotectin (urine and/or serum), cGMP (urine), leptin (serum), thromboxane (serum), and tumor necrosis factor (TNF) alpha receptor 2 (serum).

8. The method of claim 1 , further including measuring the concentration of one or more biomarkers measured in urine selected from the group consisting of activin, cAMP, digoxin, lipocalin, neopterin, Leukotriene B4 (LTB4), tumor necrosis factor (TNF) alpha receptor 2, HVEM, prostaglandin E2 (PGE2), thromboxane B2, lectin-like oxidized LDL receptor-1 (LOX-1), nitrotyrosine, F2-isoprostane, midkine, insulin-like growth factor (IGF), endothelin-1, cGMP, gamma amino butyric acid (GABA), vitamin D, cortisol, pregnenolone, substance P, epidermal growth factor (EGF), calprotectin, leptin, myeloperoxidase, neuropeptide Y, cholesystokinin (CCK), soluble vascular endothelial growth factor receptor 1 (sVEGFR1), arginine vasopressin (AVP), and adiponectin, or measuring the concentration of one or more biomarkers measured in serum selected from the group consisting of activin, cAMP, aldosteron, lipocalin, tumor necrosis factor (TNF) alpha receptor 2, interleukin-6 (IL-6), galectin-8, PGE2, thromboxane B2, LOX-1, nitrotyrosine, F2-isoprostane, brain-derived neurotrophic factor (BDNF), pigment epithelium-derived factor (PEDF), midkine, endothelin-1, cAMP, cGMP, gamma amino butyric acid (GABA), vitamin D, pregnenolone, substance P, epidermal growth factor (EGF), zonulin, calprotectin, visinin-like protein (VILIP), leptin, AVP, neuropeptide Y, matrix metalloproteinase 1 (MMP-1), bovine fibroblast growth factor (bFGF), digoxin, B cell leukemia-2 (BCL-2), calreticulin, myeloperoxidase, LTB4, phospholipase A2 (PLAF), sVEGFR1 and adiponectin.

9. The method of claim 1 , wherein the biomarkers include at least two biomarkers identified in FIG. 4 or FIG. 5 .

10. The method of claim 1 , wherein the urine is first morning urine.

11. The method of claim 1 , wherein the mood disorder is depression.

12. The method of claim 1 , wherein the mood disorder is dysthymia, endogenous depression, reactive depression, minor depression, major depression, psychotic depression, neurotic depression, postnatal depression, burn out, overstrain, unipolar depression or bipolar depression.

13. The method of claim 1 , wherein the concentration of the biomarkers is measured by one or more methods selected from the group consisting of SELDI (-TOF), MALDI (-TOF), a 1-D gel-based analysis, a 2-D gel-based analysis, Mass spec (MS), LC, reverse phase (RP) LC, size permeation (gel filtration), ion exchange, affinity, HPLC, and UPLC, or wherein the detection of the biomarker is performed by an immunological method, or wherein the detection of the biomarker is performed by mRNA/DNA based methods including (RT)-PCR, hybridization and sequencing techniques, or wherein the detection of the biomarker is performed by determining the methylation status of the gene encoding said biomarker, or wherein the detection of the biomarker is performed using a biosensor or a micro-analytical, micro-engineered, micro-separation or immunochromatography system.

14. The method of claim 1 , wherein the blood or urine samples are contacted with an antibody.