Application of ethanolamine as biomarker of affective disorder diseases

Abstract

The invention relates to the technical field of disease diagnosis, in particular to application of ethanolamine as a biomarker of affective disorder diseases.

Description

Technical Field

[0001] The present invention relates to the technical field of disease diagnosis, and particularly to the application of ethanolamine as a biomarker for affective disorder diseases. Background Art

[0002] Depression is an affective disorder disease characterized by persistent sadness and loss of interest. However, the cause of depression is unknown, there has been no major breakthrough in the diagnosis method, and the existing treatment effect is not ideal. As a highly heterogeneous mental disease, exploring biomarkers with high specificity and capable of guiding individualized treatment is of great significance for promoting the further development of clinical diagnosis and treatment of depression.

[0003] Traditional biomarkers are mostly limited to the classical neurotransmitter and endocrine hypotheses of depression. However, the sensitivity and specificity of monoamine neurotransmitters are insufficient. The overactivation of the HPA axis in depression is manifested as an abnormal increase in cortisol content, but it is interfered by the circadian rhythm and stress events. Although certain progress has been made in emerging biomarkers in recent years, there is no report on gut microbial metabolic markers. Summary of the Invention

[0004] The purpose of the present invention is to provide the application of ethanolamine as a biomarker for affective disorder diseases.

[0005] The technical problem of the present invention is solved by adopting the following technical solutions:

[0006] In the first aspect of the present invention, there is provided the application of ethanolamine as a biomarker for affective disorder diseases.

[0007] Ethanolamine is a nitrogen-containing base component that composes phospholipids. It exists in various body fluid components and tissues in a free form and can be effectively utilized by some microorganisms in the intestine as an energy source for carbon, nitrogen, etc. It is an embodiment of the gut microbial homeostasis. Fecal samples do not require invasive operations (such as cerebrospinal fluid extraction or blood testing), are more acceptable to patients, and are suitable for long-term dynamic monitoring.

[0008] In some embodiments of the present invention, there is provided the application of ethanolamine as a biomarker for depression.

[0009] In some embodiments of the present invention, there is provided the application of ethanolamine as a biomarker for the diagnosis of depression.

[0010] In some embodiments of the present invention, there is provided the application of ethanolamine as a biomarker for evaluating the treatment effect of depression.

[0011] In some embodiments of the present invention, there is provided the application of ethanolamine as a biomarker for evaluating the efficacy of escitalopram in the treatment of depression.

[0012] In some embodiments of the present invention, the ethanolamine is the ethanolamine in feces. The content of ethanolamine in the feces of patients with depression is significantly higher than that in the feces of healthy controls ( Figure 1 ). Among the depressive patients receiving treatment, they were divided into two groups by the HAMD score ( Figure 2 ). The content of ethanolamine in the feces of patients with poor treatment efficacy increased more significantly compared to those with good treatment efficacy ( Figure 3 ). Based on this, it is proposed that ethanolamine can be used as a biomarker for the diagnosis and treatment efficacy prediction of depression. BRIEF DESCRIPTION OF THE DRAWINGS

[0013] Figure 1 FIG. is a bar chart of the relative content of ethanolamine in fecal samples of healthy control subjects and patients with depression.

[0014] Figure 2 FIG. shows the HAMD values of patients with depression before and after 12 weeks.

[0015] Figure 3 FIG. shows the content of ethanolamine in the feces of remitters and non-remitters of depression after 12 weeks of treatment.

[0016] Unless otherwise stated, the terms used in the specification and claims have the following meanings.

[0017] As used in the present invention, the term "prevention" refers to preventing the occurrence of a disease and / or preventing the recurrence of a disease. DETAILED DESCRIPTION OF THE INVENTION

[0018] The specification of the present invention has described the specific implementation manners in detail. Those skilled in the art should recognize that the following implementation manners are exemplary and should not be construed as limitations on the present invention. For those skilled in the art, without departing from the principle of the present invention, through several improvements and modifications to the present invention, the technical solutions obtained by these improvements and modifications also fall within the protection scope of the claims of the present invention. The beneficial effects of the present invention are specifically described below through examples.

[0019] Example 1

[0020] Ethanolamine as a Biomarker for the Diagnosis of Depression - Detection of Depressive Patients and Healthy Controls

[0021] 1. Evaluate the severity of depression in patients through a dual assessment method

[0022] The self-administered Quick Inventory of Depressive Symptomatology - Self Report (QIDS-SR-16) was used as the primary outcome measure, providing a quantitative score range of 0 - 27, where an increase in score corresponded to an increase in the severity of depression. At the same time, the clinically assessed severity of depression was evaluated using the 17-item Hamilton Depression Rating Scale (HAMD-17), which was administered by experienced clinical raters who had completed a standardized training program.

[0023] The HAMD-17 adopted a severity classification system: 0 - 7: no depression; 8 - 16: mild depression; 17 - 23: moderate depression; ≥24: severe depression.

[0024] 2 Collect fecal samples from patients

[0025] The basic information of patients with depression and healthy controls is shown in Table 1

[0026] Table 1

[0027]

[0028] 3 Sample normalization and derivatization

[0029] Precisely weigh the fecal sample, put it into a 1.5 mL centrifuge tube, add six times the volume of cold methanol, and grind and extract for 30 min. Add chloroform, vortex in a grinder for 2 min, add water, and extract in an ultrasonic grinder for 30 min. Use a low-temperature centrifuge at 4°C and 13,000 rpm for low-temperature centrifugation for 15 min, take 500 μL of the supernatant, and transfer it into a glass derivatization bottle.

[0030] Evaporate the sample to dryness using a centrifugal concentrator dryer. Add 80 μL of methoxyamine hydrochloride pyridine solution to the glass derivatization bottle, vortex for 2 min, and then carry out an oximation reaction in a shaking incubator at 37°C for 90 min. After taking out the sample, add 80 μL of BSTFA derivatization reagent and 20 μL of n-hexane, vortex for 2 min, and then react at 70°C for 60 min. Let it stand at room temperature for 30 min.

[0031] 4 Determine the ethanolamine content in fecal samples

[0032] Use an Agilent 7890A-5975C gas chromatography-mass spectrometry (GC-MS) system (Agilent Technologies, USA) for untargeted metabolomics analysis. The sample is separated on an HP-5MS capillary column (30 m × 0.25 mm × 0.25 μm, Agilent J&W Scientific, Folsom, CA, USA), and then detected and quantitatively analyzed by mass spectrometry. The data is acquired in the full scan mode (m / z 50 - 600).

[0033] 5 Judge the difference in ethanolamine content between patients with depression and healthy controls

[0034] Figure 1 It is a bar chart of the relative ethanolamine content in fecal samples of healthy control groups and patients with depression. As can be seen from Figure 1 it, the ethanolamine content in the feces of patients with depression is abnormally increased.

[0035] Example 2

[0036] Ethanolamine as a Biomarker for the Treatment of Depression - Efficacy Assessment of Depressed Patients Undergoing Treatment

[0037] 1 Depressed patients received escitalopram treatment for 12 weeks. The dosing regimen of escitalopram was an initial dose of 5 mg per day, gradually increased to a range of 10 - 20 mg per day within 7 days.

[0038] 2 After 12 weeks of treatment, the severity of major depressive disorder was evaluated in patients using the HAMD17.

[0039] 3 Patients were classified according to the depression scale score: those with a HAMD - 17 ≤ 7 after treatment were defined as Remitters, and those with a HAMD - 17 ≥ 7 were defined as Non - Remitters.

[0040] The basic conditions of the treatment remission group and the non - remission group are shown in Table 2

[0041] Table 2

[0042]

[0043]

[0044] Figure 2 The HAMD values of depressed patients before and after 12 weeks. This figure only shows the reduction in the Hamilton Depression Rating Scale scores of patients after differentiating the treatment effects, which proves the differentiation of treatment effects through the reduction scores. All patients refer to all patients without differentiating the treatment effects, which can be understood as the average value. As can be seen from the figure, at baseline, the disease scores of all depressed patients were at a relatively high level, indicating that the overall depressive condition was relatively severe. After 12 weeks of treatment, the depressive scores of all three groups decreased significantly (i.e., the scores before and after treatment in each group had a statistically significant decrease ***), but the degree of decrease was different. When comparing the depressive scores after 12 weeks of treatment alone, there were statistically significant differences among the three groups ***.

[0045] 4 Detect the changes in ethanolamine content in remitters and non - remitters of depression before and after treatment.

[0046] Figure 3The content of ethanolamine in the feces of patients with remission and non-remission of depression after 12 weeks of treatment. The ordinate of this figure is not the absolute content value, but the value after data normalization. All patients refer to all patients regardless of the treatment effect, which can be understood as the average value. As can be seen from the figure, at baseline, there was a significant difference in the content of ethanolamine between the non-remission group and the remission group (the content of ethanolamine in the non-remission group was higher, and the statistical P value was 0.0162*). After treatment, the content of ethanolamine in the three groups tended to be the same, that is, there was no statistical difference in the content of ethanolamine among the three groups after 12 weeks of treatment.

[0047] The description of specific embodiments in the specification of the present invention is detailed. Those skilled in the art should recognize that the above embodiments are exemplary and should not be construed as limitations on the present invention. For those skilled in the art, without departing from the principle of the present invention, through several improvements and modifications to the present invention, the technical solutions obtained by these improvements and modifications also fall within the protection scope of the claims of the present invention.

Claims

1. Use of ethanolamine as a biomarker for affective disorder diseases.

2. The application according to claim 1, characterized in that Use of the ethanolamine as a biomarker for depression.

3. The application according to claim 1, wherein Use of the ethanolamine as a biomarker for the diagnosis of depression.

4. The application according to claim 1, characterized in that, Use of the ethanolamine as a biomarker for evaluating the therapeutic effect of depression treatment.

5. The application according to claim 1, characterized in that Use of the ethanolamine as a biomarker for evaluating the efficacy of escitalopram in the treatment of depression.

6. The application according to any one of claims 1 to 5, characterized in that, The ethanolamine is ethanolamine in feces.

Images