Biomarker for diagnosing depression and uses thereof

Abstract

The present invention relates to a marker composition for diagnosing major depressive disorder, comprising ZA2G and prothrombin as markers, a method for providing information necessary to determine the occurrence of major depressive disorder using the marker composition, a composition for determining the occurrence of major depressive disorder, comprising agents for measurement of the expression levels of the markers, and a kit for determining the occurrence of major depressive disorder, comprising devices for measurement of the expression levels of the markers. The method for providing information for use in determining the occurrence of major depressive disorder provided by the present invention can be widely utilized to determine the occurrence of various mental disorders, including major depressive disorder since it is possible to measure the expression levels of proteins of which the expression levels are changed at the time of the occurrence of major depressive disorder, and to more objectively and accurately determine the occurrence of major depressive disorder when the method is used.

Claims

1. A method for providing information necessary to determine occurrence of major depressive disorder, the method comprising: (a) quantitatively analyzing an expression level of a marker protein selected from the group consisting of ZA2G (zinc-alpha-2-glycoprotein), prothrombin, and a combination thereof in a serum sample of an individual suspected of having major depressive disorder; and (b) correlating the quantitatively analyzed expression level of the marker protein with determination of occurrence of major depressive disorder.

2. The method according to claim 1, wherein the step (b) is performed by combining quantitative analysis results of respective marker proteins.

3. The method according to claim 2, wherein the combining is performed using an analysis method selected from the group consisting of a linear or nonlinear regression analysis method; a linear or nonlinear classification analysis method; ANOVA; a neural network analysis method; a genetic analysis method; a support vector machine analysis method; a hierarchical cluster analysis or cluster analysis method; a hierarchical algorithm using decision trees, or Kernel principal component analysis method; a Markov Blanket analysis method; a recursive feature elimination or entropy-based recursive feature elimination analysis method; a forward floating search or backward floating search analysis method; and a combination thereof.

4. The method according to claim 2, wherein the combining is performed using a computer algorithm.

5. The method according to claim 1, wherein the step (a) further includes quantitatively analyzing an expression level of K2C1 (keratin type II, cytoskeletal 1).

6. The method according to claim 1, wherein the step (b) further includes correlating a quantitatively analyzed expression level of K2C1 with determination of occurrence of major depressive disorder.

7. The method according to claim 6, wherein the correlating step is performed by combining quantitative analysis results of ZA2G, prothrombin, and K2C1.

Description

BRIEF DESCRIPTION OF DRAWINGS

[0047] FIG. 1A is graphs illustrating the analysis results of changes in the expression levels of ZA2G and K2C1 in patients in depression status and the same patients in remission status:

[0048] FIG. 1B is graphs illustrating the comparative analysis results of changes in the expression levels of ZA2G and K2C1 in patients in depression status, the same patients in remission status, and a control group;

[0049] FIG. 2A is graphs illustrating the analysis results of changes in the expression level of prothrombin in patients in depression status and patients in remission status; and

[0050] FIG. 2B is graphs illustrating the comparative analysis results of changes in the expression level of prothrombin in patients in depression status, patients in remission status, and a control group.

DETAILED DESCRIPTION OF THE INVENTION

[0051] Hereinafter, the configuration and effects of the present invention will be described in more detail with reference to exemplary embodiments. However, these exemplary embodiments are for illustrative purposes only, and the scope of the present invention is not intended to be limited by these exemplary embodiments.

Example 1: Discovery of Marker for Diagnosis of Major Depressive Disorder from the Same Patient with Major Depressive Disorder

[0052] First, blood was collected from 13 patients with major depressive disorder in depression status (ADT) and the same 13 patients in remission status (ART), and sera were obtained from the blood samples. Here, ADT refers to a status in which a person has been diagnosed with major depressive disorder, has symptoms of major depressive disorder, and has undergone drug treatment for major depressive disorder, and ART refers to a status in which a patient was diagnosed with major depressive disorder, but does not currently have symptoms of major depressive disorder, and treatment for major depressive disorder has been completed.

[0053] A portion of each of the obtained sera was fractionated, and the respective fractionated sera were combined into one to obtain a pooled sample.

[0054] Each of the obtained serum samples and pooled samples was applied to a MARS (Multiple Affinity Removal System) column to deplete highly abundant proteins in the serum contained in each sample.

[0055] Each of the serum samples and pooled samples treated in the MARS column were treated with trypsin, and proteins contained in each sample were decomposed into peptides to obtain peptide serum samples and peptide pooled samples.

[0056] The OFFGEL fractionation method was performed on the peptide pooled sample. Roughly, the peptide pooled sample was electrophoresed and sorted by pl value to obtain 12 fractions.

[0057] DIA MS analysis was performed on the 12 fractionated samples thus obtained, and a peptide library was constructed based on the results.

[0058] DIA MS analysis was performed on the obtained peptide serum sample, and the MS/MS data thus acquired was applied to the peptide library constructed previously by the spectrum matching method to perform relative quantitative analysis. A targeted marker peptide candidate was selected by statistical analysis of the relative quantitative analysis data thus acquired. Here, the selection criteria were set to the following six items:

[0059] (1) there is no identical sequence in different proteins;

[0060] (2) R or K is present at one of both ends of the peptide sequence (use of trypsin);

[0061] (3) there is no M in the middle of the sequence (amino acid that is easily oxidized);

[0062] (4) the length of the peptide sequence is 15 or less;

[0063] (5) it is a sequence without post-translational modifications; and

[0064] (6) the peptide has an intensity of 1000 or more and FDR of 1 or less.

[0065] Absolute quantitative analysis using MRM (Multiple Reaction Monitoring) was performed on the targeted marker peptides selected according to the criteria.

[0066] Roughly, the concentration of the peptide was determined using the standard curve of the targeted marker peptide selected, and then it was confirmed whether the expression tendency of the targeted marker peptide derived from the result of the relative quantitative analysis performed previously was consistent with the MRM result (FIG. 1A).

[0067] FIG. 1A is graphs illustrating the analysis results of changes in the expression levels of ZA2G and K2C1 in patients in depression status and the same patients in remission status.

[0068] As illustrated in FIG. 1A, it was confirmed that the expression levels of ZA2G and K2C1 were downregulated in the patients in depression status compared to in the same patients in remission status.

[0069] In order to verify this, the expression levels of ZA2G and K2C1 in patients in depression status and in the same patients in remission status previously measured were compared with the expression levels of ZA2G and K2C1 in a control group (FIG. 1B). At this time, serum samples obtained from 67 healthy controls were used as the control group.

[0070] FIG. 1B is graphs illustrating the comparative analysis results of changes in the expression levels of ZA2G and K2C1 in patients in depression status, the same patients in remission status, and the control group.

[0071] As illustrated in FIG. 1B, it was confirmed that the expression levels of ZA2G and K2C1 were statistically significantly lower in the patients in depression status compared to the control group.

[0072] In contrast, statistically significant changes in the expression levels of ZA2G and K2C1 were not confirmed in the patients in remission status compared to in the control group.

Example 2: Discovery of Marker for Diagnosis of Major Depressive Disorder from Patient with Major Depressive Disorder

[0073] Marker proteins for diagnosis of major depressive disorder were discovered using the method of Example 1 except that sera obtained from 22 patients in depression status and 20 patients in remission status were used instead of the sera obtained from 13 patients with major depressive disorder in depression status (ADT) and the same 13 patients in remission status (ART) (FIG. 2A).

[0074] FIG. 2A is graphs illustrating the analysis results of changes in the expression level of prothrombin in patients in depression status and patients in remission status.

[0075] As illustrated in FIG. 2A, it was confirmed that the expression level of prothrombin is statistically significantly upregulated in the patients in depression status compared to in the patients in remission status.

[0076] In order to verity this, the expression level of prothrombin was compared using serum samples obtained from 47 new patients in depression status, 40 new patients in remission status, and a control group (FIG. 2B). At this time, serum samples obtained from 67 healthy controls were used as the control group.

[0077] FIG. 2B is graphs illustrating the comparative analysis results of changes in the expression level of prothrombin in patients in depression status, patients in remission status, and the control group.

[0078] As illustrated in FIG. 2B, it was confirmed the expression level of prothrombin was statistically significantly higher in the patients in depression status than in the control group.

[0079] In contrast, the expression level of prothrombin was statistically significantly lower in the patients in remission status than in the control group.

[0080] Based on the above description, it will be understood by those skilled in the art that the present disclosure may be implemented in a different specific form without changing the technical spirit or essential characteristics thereof. Therefore, it should be understood that the above embodiment is not limitative, but illustrative in all aspects. The scope of the disclosure is defined by the appended claims rather than by the description preceding them, and therefore all changes and modifications that fall within metes and bounds of the claims or equivalents of such metes and bounds are therefore intended to be embraced by the claims.