CN110702930A

CN110702930A - Application of 24-hydroxycholesterol in preparation of depression diagnosis and treatment related products

Info

Publication number: CN110702930A
Application number: CN201910837982.2A
Authority: CN
Inventors: 孙作厘; 杨健; 王刚; 周晶晶; 贺毅; 丰雷
Original assignee: Beijing Anding Hospital
Current assignee: Beijing Anding Hospital
Priority date: 2019-09-05
Filing date: 2019-09-05
Publication date: 2020-01-17
Anticipated expiration: 2039-09-05
Also published as: CN110702930B

Abstract

The invention provides an application of 24-hydroxycholesterol or a reagent for detecting 24-hydroxycholesterol in preparing a reagent or a kit for diagnosing depression and an application in preparing a reagent or a kit for predicting and/or judging the treatment effect of an antidepressant. The 24-hydroxycholesterol can be used as a biomarker for diagnosing depression and predicting curative effect, has higher sensitivity and specificity for depression diagnosis, can be diagnosed and predicted only by measuring one index of the level of the 24-hydroxycholesterol in peripheral blood, and is convenient to popularize and use.

Description

Application of 24-hydroxycholesterol in preparation of depression diagnosis and treatment related products

Technical Field

The invention belongs to the technical field of biology, and particularly relates to application of a brain cholesterol metabolite 24-hydroxycholesterol (24OHC) in depression diagnosis and antidepressant curative effect prediction, and application in preparation of a corresponding reagent.

Background

Depression (MDD) is an affective disorder caused by a variety of factors with a Major symptom of persistent depression. Epidemiological data indicate that the prevalence of MDD worldwide is as high as 5% -12%, with about 15% of people having had depressive episodes in their lives, with 15% of MDD patients dying themselves. The World Health Organization (WHO) predicts that MDD will become the second economically burdened disease in the world after cardiovascular disease by 2020. MDD, a global psychiatric disease with high morbidity, mortality, and disability, has become a major public health problem that is urgently needed.

Currently, the main difficulties faced in the diagnosis and treatment of depression are: (1) the pathogenesis is not clear: the pathogenesis hypothesis of depression is many, and mainly comprises deficiency of neurotrophic factors, monoamine neurotransmitter disorder, oxidative stress disorder and the like. These hypotheses provide a certain theoretical basis for revealing the pathophysiological mechanism of depression, but have not gained wide acceptance. (2) Lack of objective test diagnosis: the diagnosis of depression relies primarily on the subjective identification by physicians of the clinical symptoms of the patient. However, the heterogeneity of clinical manifestations of depression is high, and a small proportion of patients have major clinical manifestations of hyperactivity, euphoria, hallucinations, delusions, and are easily confused with symptoms of other mental diseases, such as bipolar disorder and schizophrenia, making the accuracy of clinical diagnostic methods based on symptoms low. For example, one meta analysis found that MDD patients diagnosed only 47% correctly, while DSM-5 (fifth edition of the american mental disorder diagnosis and statistics manual) field tests found that depression diagnosis was only 28% consistent. (3) Antidepressants have a slow onset of action: traditional antidepressants, represented by selective 5-hydroxytryptamine reuptake inhibitors (SSRIs) and norepinephrine reuptake inhibitors, generally take 2-4 weeks to become effective, which results in some patients being adept at drug reduction, drug withdrawal, or even treatment interruption in the early treatment period due to subjective feeling of ineffective treatment, which not only increases suicide risk, but also affects long-term prognosis, and imposes a huge economic and social burden on patients.

In the research aspect of depression diagnosis and treatment markers, blood indexes are easy to obtain, wounds are small, the price is low, and automatic detection is easy, so that the blood indexes are widely concerned.

Disclosure of Invention

The technical problem to be solved by the invention is that no blood biomarker is consistently recognized in the aspects of depression diagnosis and curative effect prediction at present, namely, a method for objectively judging depression and a method for judging the curative effect of an antidepressant drug are lacked in the prior art.

In order to solve the above technical problems, it is necessary to screen biomarkers related to depression, thereby helping to reveal the underlying pathophysiological mechanism and developing objective methods for diagnosis and prediction of therapeutic effects. The abnormal change of the total cholesterol in peripheral blood in depression patients is considered by researchers to be used as a biomarker, but the conclusion of different researchers is inconsistent, so that the abnormal change is difficult to be used as an objective biomarker for depression diagnosis and efficacy prediction.

The inventor finds that the main metabolite of the brain cholesterol is 24-hydroxycholesterol (24-hydroxycholesterol), and more than 90% of 24OHC in peripheral blood comes from the brain, which provides convenient conditions for detecting central lesion in peripheral blood. The results of cadaveric brain studies of patients with suicidal depression show that 24OHC in the brains of the patients is obviously increased. Therefore, 24OHC, a brain cholesterol metabolite in peripheral blood, has the potential to be a biomarker associated with depression.

The inventor further researches to find that the concentration of 24OHC in the peripheral blood plasma of depression patients is obviously increased compared with that of normal people. Meanwhile, for depression patients receiving antidepressant drug treatment, the reaction of the depression patients to the drug is divided into two groups of treatment effective groups and treatment ineffective groups, and the comparison between the groups shows that the 24OHC level in the plasma of the treatment effective patients is obviously higher than that of the control group and the treatment ineffective patients, and the 24OHC level in the peripheral blood of the treatment effective patients is gradually reduced along with the treatment. Therefore, the level of the 24OHC in the blood plasma can be used as a biomarker for diagnosing depression patients and also used for predicting the curative effect of the depression patients.

Based on the research findings, the invention provides the following technical scheme:

in one aspect, the invention provides the use of 24-hydroxycholesterol or a reagent for detecting 24-hydroxycholesterol in the manufacture of a reagent or kit for the diagnosis of depression.

In another aspect, the invention provides the use of 24-hydroxycholesterol or a reagent for detecting 24-hydroxycholesterol in the manufacture of a reagent or kit for predicting and/or determining the therapeutic efficacy of an antidepressant.

Preferably, the above use, wherein said kit is selected from the group consisting of a biochemical diagnostic kit, an immunodiagnostic kit or a molecular diagnostic kit; preferably, the kit is selected from one or more of Western blot kit, enzyme-linked immunosorbent assay (ELISA) kit, Radioimmunoassay (RIA) kit, radioimmunodiffusion kit, two-dimensional biphasic immunodiffusion kit, rocket immunoelectrophoresis kit, immunohistochemical staining kit, immunoprecipitation assay kit, complement fixation assay kit, Fluorescence Activated Cell Sorting (FACS) kit, aptamer chip kit, microarray kit and protein chip kit.

Preferably, the use as described above, wherein the kit comprises a depression rating scale; preferably, the depression rating scale is selected from one or more of the hamilton depression scale (HAMD), the montgomery depression scale (MADRS), the Zung depression self-rating scale (SDS), the Beck depression self-rating scale (BDI), the depression symptom rapid rating scale (QIDS), the hypomania self-rating scale (HCL-32), the Mood Disorder Questionnaire (MDQ), the young mania scale (YMRS), and the depression screening scale (PHQ 9); more preferably, the depression rating scale is the hamilton depression scale (HAMD).

Preferably, the use as described above, wherein the diagnosis of depression comprises the steps of:

step 1: determining the concentration of 24-hydroxycholesterol in the peripheral blood of the subject;

step 2: comparing the concentration of the 24-hydroxycholesterol measured in the step 1 with a standard concentration; and

and step 3: the subject is judged to be at risk for depression, e.g., if the plasma 24-hydroxycholesterol concentration is greater than 40.85ng/ml, the probability of depression is about 53%.

Preferably, the above use, wherein predicting and/or judging the therapeutic effect of the antidepressant comprises the steps of:

step 1: measuring the concentration of 24-hydroxycholesterol in the peripheral blood of the subject at different time points of the treatment, and comparing the concentration of 24-hydroxycholesterol in the peripheral blood of the subject measured at the different time points;

preferably, in step 1, the drug therapy is indicated to be ineffective if the concentration of 24-hydroxycholesterol in the peripheral blood of the subject shows an increasing trend as the therapy progresses, and the drug therapy is indicated to be effective if the concentration of 24-hydroxycholesterol in the peripheral blood of the subject shows a decreasing trend as the therapy progresses.

In another aspect, the invention provides a kit for diagnosing depression or for predicting and/or judging the therapeutic effect of an antidepressant, said kit comprising 24-hydroxycholesterol and a depression rating scale; preferably, the depression rating scale is selected from one or more of the hamilton depression scale (HAMD), the montgomery depression scale (MADRS), the Zung depression self-rating scale (SDS), the Beck depression self-rating scale (BDI), the depression symptom rapid rating scale (QIDS), the hypomania self-rating scale (HCL-32), the Mood Disorder Questionnaire (MDQ), the young mania scale (YMRS), and the depression screening scale (PHQ 9); more preferably, the depression rating scale is the hamilton depression scale (HAMD).

In another aspect, the present invention provides a kit for diagnosing depression or for predicting and/or judging the therapeutic effect of an antidepressant, the kit comprising a reagent for detecting 24-hydroxycholesterol and a depression assessment scale; preferably, the depression rating scale is selected from one or more of the hamilton depression scale (HAMD), the montgomery depression scale (MADRS), the Zung depression self-rating scale (SDS), the Beck depression self-rating scale (BDI), the depression symptom rapid rating scale (QIDS), the hypomania self-rating scale (HCL-32), the Mood Disorder Questionnaire (MDQ), the young mania scale (YMRS), and the depression screening scale (PHQ 9); more preferably, the depression rating scale is the hamilton depression scale (HAMD).

Preferably, the above-mentioned use or the above-mentioned kit, wherein the reagent for detecting 24-hydroxycholesterol is one or more selected from the group consisting of 24-hydroxycholesterol ligand or an antibody to 24-hydroxycholesterol ligand, an antibody to 24-hydroxycholesterol, a chromogenic reagent, a luminescent marker, a dye, a fluorescent marker, a standard, a basic hydrolysis reagent, a derivatization reagent, an internal standard and an external standard; preferably, the standard is selected from serum albumin; further preferably, the alkaline hydrolysis reagent is selected from one or more of butyl hydroxy toluene, potassium hydroxide, ethylene diamine tetraacetic acid and ethanol; further preferably, the derivatization reagent is one or more than two selected from N' -diisopropyl carbodiimide, nicotinamide and 4-dimethylaminopyridine; further preferably, said internal standard is selected from D5 deuterium cholesterol and/or D7 deuterium cholesterol; further preferably, the external standard is selected from D5 deuterium cholesterol and/or D7 deuterium cholesterol.

Preferably, the use as described above or the kit as described above, wherein the kit contains reagents for detecting 27-hydroxycholesterol, serum amyloid P and/or vascular cell adhesion molecules.

The beneficial effects of the invention include:

the invention provides a corresponding diagnosis and pre-test agent by detecting the level of 24-hydroxycholesterol as a basis for diagnosing depression and predicting the curative effect, compared with the traditional diagnosis method which relies on symptoms and inquiry to confirm and identify depression, the method has higher sensitivity and specificity for depression diagnosis, and can better distinguish the curative effect of antidepressant before medication, thereby selectively using antidepressant, greatly improving the treatment effect and shortening the treatment period.

On the other hand, the 24-hydroxycholesterol biomarker belongs to a peripheral blood index and can be conveniently obtained, and meanwhile, diagnosis and prediction can be carried out only by measuring one index of the peripheral blood 24-hydroxycholesterol level, so that the method is convenient to popularize and use. Meanwhile, the method for predicting depression by using the 24-hydroxycholesterol biomarker as diagnosis and curative effect can be combined with other detection modes to obtain more reliable results.

Drawings

In order to more clearly illustrate the technical solution of the present invention, the drawings which are needed to be used are briefly described below, and it is obvious that the drawings in the following description are only some embodiments described in the present invention, and it is obvious for those skilled in the art that other drawings can be obtained according to the drawings without creative efforts.

FIG. 1-1: healthy controls and depressed patients had a pre-treatment plasma 24OHC concentration.

FIGS. 1-2: plasma ROC curves before treatment for healthy controls and depressed patients.

FIG. 2-1: patients with depression are scored on the hamilton depression scale (HAMD) after 12 weeks of antidepressant treatment.

FIG. 2-2: patients with depression had a quick rating scale for depression symptoms (QIDS) score after 12 weeks of antidepressant treatment.

FIGS. 2 to 3: patients with depression are scored for young mania scale (YMRS) after 12 weeks of antidepressant treatment.

FIGS. 2 to 4: depression patients were scored on the depression screening scale (PHQ9) after 12 weeks of antidepressant treatment.

FIG. 3: plasma 24OHC concentration changes before and after treatment in each group of people.

FIG. 4: difference in plasma 24OHC concentration after 12 weeks treatment in patients with different therapeutic effects.

FIG. 5: correlation of concentration difference of plasma 24OHC at 12 weeks with fraction of HAMD decrease.

Detailed Description

In order to make the technical solutions of the present invention better understood, the technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.

In one embodiment of the present invention, 24-hydroxycholesterol is used as a biomarker in a reagent or kit for diagnosing depression or for predicting and/or judging the therapeutic effect of an antidepressant. By detecting the 24OHC concentration in the peripheral blood of the object to be tested by using the reagent or the kit, depression is diagnosed or the therapeutic effect of the antidepressant is predicted and/or judged. Specifically, peripheral blood of a subject to be tested may be extracted, plasma may be separated and a 24OHC concentration may be measured, the blood extraction time may be before treatment to diagnose the diseased state of the subject, the 24OHC concentration may also be used as an index for predicting the efficacy of a subject identified as a depression patient to select a drug suitable for the patient, and the blood extraction time may be performed during or after the treatment to monitor the treatment effect.

Herein, the term "depression" also known as depressive disorder, is a mood disorder characterized primarily clinically by a marked and persistent mood drop.

The term "antidepressant" (antidepressant) refers to a group of psychotropic drugs that are used primarily to treat mental disorders that are predominantly symptomatic of mood depression. Antidepressants known in the art include monoamine oxidase inhibitors (MAOI), tricyclic antidepressants (TCA), selective 5-HT reuptake inhibitors (SSRI), and the like, and specific examples of applications include, but are not limited to, isoprotuzine, phenelzine, imipramine, amitriptyline, doxepin, clomipramine, fluoxetine, paroxetine, sertraline, fluvoxamine, citalopram, and the like.

Herein, the term "24-hydroxycholesterol" (24-hydroxycholesterol, 24OHC) is a major metabolite of brain cholesterol and has the following structural formula:

there are mainly 2 cholesterol clearance pathways in the brain: one is transport out of the brain through cerebrospinal fluid via apolipoprotein e (apoe); another more major pathway is the oxidative metabolic mode: approximately 6-7mg daily of cholesterol enters the blood circulation through the blood-brain barrier in the form of 24-hydroxycholesterol, catalyzed by cholesterol-24 hydroxylase (CYP46), a cytochrome oxidase P450, which is unique to neurons in the brain. 24-hydroxycholesterol is substantially identical to cholesterol distribution in the brain, and is mainly present in myelin sheaths.

The term "diagnosis" refers to a method of detecting and/or identifying a pathological state in a subject, identifying and/or determining the course of whether a subject has a given disease or disorder, estimating or determining the future clinical progression of a subject, either before or after the onset of symptoms.

The term "predicting" refers to estimating or determining the likelihood that a patient will respond favorably or unfavorably to a drug (therapeutic agent) or group of drugs or treatment regimen.

The term "determining" refers to estimating or determining the likelihood that a patient has responded, or is responding favorably or unfavorably, to a drug (therapeutic agent) or group of drugs or treatment regimen.

In a specific embodiment of the present invention, the reagent for diagnosing depression, the reagent for predicting and/or judging the therapeutic effect of an antidepressant, and the like are prepared into a kit, and the kit may be a biochemical diagnosis kit, an immunodiagnostic kit, a molecular diagnosis kit, and the like, and is preferably prepared into the immunodiagnostic kit.

The diagnostic kit is prepared by adopting the principles or methods of immunology, microbiology, molecular biology and the like, and is used for diagnosing, detecting and epidemiological investigation of human diseases in vitro and the like.

The diagnostic kit may be of a type well known in the art, including, but not limited to, Western blot kit, enzyme linked immunosorbent assay (ELISA) kit, Radioimmunoassay (RIA) kit, radioimmunodiffusion kit, ouchterlony immunodiffusion kit, rocket immunoelectrophoresis kit, immunohistochemical staining kit, immunoprecipitation assay kit, complement fixation assay kit, Fluorescence Activated Cell Sorting (FACS) kit, aptamer chip kit, microarray kit, protein chip kit, and the like.

In the kit, the reagent for detecting 24OHC is included, and the reagent refers to a molecule capable of specifically determining the concentration of 24OHC, and includes but is not limited to nucleic acid molecules, proteins, compounds and the like which can specifically bind to 24 OHC.

In one embodiment of the present invention, a protein capable of specifically binding to 24OHC may be selected as the reagent for detecting 24OHC, and in another embodiment of the present invention, an antibody, which may be an antibody specifically binding to a marker protein, including but not limited to polyclonal antibody, monoclonal antibody, recombinant antibody and antigen binding fragment thereof, is preferred as the reagent for detecting 24OHC, as long as it retains an antigen binding function.

In the present invention, the reagent for detecting 24OHC may be linked with a detectable label molecule.

The present invention will be described in more detail with reference to specific examples, which, however, are for illustrative purposes only and do not limit the present invention.

The reagents and equipment sources used in the following examples are shown in Table 1 below, and reagents or equipment or procedures not described herein are routinely determined by one of ordinary skill in the art:

TABLE 1 reagents and apparatus used in the examples

Reagent/instrument	Model/specification	Manufacturer of the product
			Ammonium acetate	The content of 500g is more than or equal to 98 percent	Chemical reagent for national medicine group
Formic acid	50ml	Fluka
			Methyl tert-butyl ether	The content of 1L is more than or equal to 99.9 percent	Merck
N' -diisopropylcarbodiimide	The content of D12540725 g is more than or equal to 99 percent	Merck
			Nicotinamide	72340100 g content is more than or equal to 99 percent	Merck
4-dimethylaminopyridine	10770025 g content is more than or equal to 99 percent	Merck
			Methanol	The content of 348604L is more than or equal to 99.9 percent	Merck
High performance liquid chromatograph	Agilent G1312B	Agilent
			Mass spectrometer	AB Sciex Qtrap 6500	ABI of America

Examples

Example 1: method for collecting peripheral blood and measuring 24OHC concentration in peripheral blood

1. According to the approved ethical examination experimental scheme and diagnosis standard, 91 cases of healthy control population and depression (no drug or more than 6 weeks) patients are screened, the depression severity of the patients is evaluated by using Hamilton depression scale (HAMD), depression symptom rapid rating scale (QIDS), Young mania scale (YMRS) and depression screening scale (PHQ9) 2 weeks before and 12 weeks after the treatment of the antidepressant citalopram, 5ml of peripheral blood is extracted from an EDTA anticoagulation tube, and the upper plasma is separated at 3000 r/min, separated and immediately stored in an ultra-low temperature refrigerator at-80 ℃ for later use.

2. Extracting plasma, and detecting the content of 24OHC by high performance liquid chromatography-mass spectrometry, wherein the specific method comprises the following steps:

(1) a standard solution of 24OHC with a concentration of 1-2000ng/ml was prepared using a 5% bovine serum albumin solution, and the 5% bovine serum albumin solution was used as a blank sample.

(2) To a 1.5ml EP tube was added 50. mu.l standard/blank/plasma to be tested, followed by 50. mu.l internal standard (D5 deuterium cholesterol + D7 deuterium cholesterol 50ng/ml), followed by 200. mu.l acidic buffer (50mM ammonium acetate, 1% formic acid) and 1ml methyl tert-butyl ether.

(3) After mixing well, the sample was placed in a-80 ℃ freezer, and after the aqueous phase was cooled and crystallized, 0.5ml of methyl tert-butyl ether phase (supernatant) was transferred to a 1.5ml centrifuge tube.

(4) Methyl tert-butyl ether was blown dry at 35 ℃ under nitrogen.

(5) To each EP tube was added 50. mu.l of a derivatizing agent (63mg of N, N' -diisopropylcarbodiimide, 62mg of nicotinamide and 61mg of 4-dimethylaminopyridine in 5ml of chloroform), and mixed by heating at 35 ℃ for 2 hours.

(6) The dichloromethane was blown dry with nitrogen at 35 ℃.

(7) Sample detection was performed after 100. mu.l methanol reconstitution.

In the following examples, peripheral blood was collected and the concentration of 24OHC in peripheral blood was measured by the method described in the present example.

Example 2: peripheral blood 24OHC as biomarker for depression diagnosis

1. Age and gender matched depression patients and 91 healthy controls were included in the study, and the basic demographic and patient symptom assessments for each group are shown in table 2.

Table 2: assessment of basic population and clinical symptoms in patients

Note: HAMD: hamilton depression scale; QIDS: a quick rating scale for depression symptoms; YMRS: young mania scale; PHQ 9: a depression screening scale; NA: missing values.

Through plasma cholesterol detection, the plasma 24OHC of the depression patients is obviously increased compared with that of healthy control groups (figure 1-1, p is less than 0.0001), which indicates that the cholesterol metabolism in the brains of the patients is obviously increased and can be a potential biomarker for depression diagnosis. Combining the Body Mass Index (BMI) and family history index of the subject, and using 24OHC concentration as a diagnosis index, a Receiver Operating Characteristic curve (ROC) curve (figure 1-2) was prepared, the area under the curve was 0.784, and the diagnosis sensitivity and specificity were 81.3% and 62.6%, respectively.

Example 3: prediction of efficacy of peripheral blood 24OHC as biomarker for antidepressants

The depression patients in the group were treated with the antidepressant citalopram and the scale assessment of depression symptoms was performed at 2 weeks, 4 weeks, 8 weeks and 12 weeks after treatment (fig. 2-1 to fig. 2-4). After the patient is treated for 12 weeks for antidepressant, all scores are obviously reduced, and symptoms are improved. However, the symptoms of some patients are not improved obviously, and the patients are divided into treatment effective (Responders) groups and treatment ineffective (Non-Responders) groups according to the treatment effect (the reduction rate reaches 50% on Hamilton depression scale) of the patients after 12 weeks. Wherein 65 patients are therapeutically effective and 26 patients are not therapeutically effective. As can be seen from fig. 2-1 to fig. 2-4, the treatment-ineffective group, although having some effect, did not meet the criteria for clinical remission.

The plasma 24OHC concentration of depression patients was significantly higher than that of healthy controls before treatment, the plasma 24OHC concentration of patients in the effective group decreased with time after treatment, while the plasma 24OHC concentration of patients in the treatment-ineffective group slightly increased with time (fig. 3). After 12 weeks of treatment, there was a clear difference in the change in 24OHC levels (pre-treatment-post-treatment) among the different efficacy patient groups (fig. 4, p <0.05), further suggesting that plasma 24OHC could be a biomarker for the prediction of efficacy in depression patients.

The results suggest that the hydroxycholesterol is significantly different among patients with different therapeutic effects, and then the relationship between the hydroxycholesterol level and the symptom level is further observed. To this end, the fractional subtraction of HAMD scores after 12 weeks treatment ((pre-treatment-post-treatment)/pre-treatment 100) was calculated and analyzed for correlation with the difference in plasma 24OHC concentrations before and after 12 weeks (pre-treatment-post-treatment) (figure 5): the larger the difference between the former and later, the more the decrease in the 24OHC concentration, and the higher the reduction rate, the better the therapeutic effect. The results show that the change value of 24OHC with treatment has obvious positive correlation with the reduction rate of HAMD, and further indicate the close relationship between 24OHC and the curative effect.

As can be seen from the above examples 2 and 3, the present invention realizes an objective diagnosis method for depression by selecting peripheral blood 24OHC as a biomarker to diagnose the condition of depression patients, and has high sensitivity and specificity for depression diagnosis. Meanwhile, on the other hand, by analyzing the change of the peripheral blood 24OHC concentration before and after the antidepressant is used by the patient, the peripheral blood 24OHC of the depression patient can also be used as an index for predicting the curative effect, and the curative effect of the antidepressant is predicted before the antidepressant is used or the curative effect of the antidepressant is judged after the antidepressant is used.

Claims

Use of 24-hydroxycholesterol or a reagent for detecting 24-hydroxycholesterol in the preparation of a reagent or kit for the diagnosis of depression.
Use of 24-hydroxycholesterol or a reagent for detecting 24-hydroxycholesterol in the manufacture of a reagent or kit for predicting and/or determining the therapeutic effect of an antidepressant.
3. The use according to claim 1 or 2, wherein the kit is selected from a biochemical diagnostic kit, an immunodiagnostic kit or a molecular diagnostic kit; preferably, the kit is selected from one or more of Western blot kit, enzyme-linked immunosorbent assay (ELISA) kit, Radioimmunoassay (RIA) kit, radioimmunodiffusion kit, two-dimensional biphasic immunodiffusion kit, rocket immunoelectrophoresis kit, immunohistochemical staining kit, immunoprecipitation assay kit, complement fixation assay kit, Fluorescence Activated Cell Sorting (FACS) kit, aptamer chip kit, microarray kit and protein chip kit.
4. The use according to any one of claims 1-3, wherein the kit comprises a depression rating scale; preferably, the depression rating scale is selected from one or more of the hamilton depression scale (HAMD), the montgomery depression scale (MADRS), the Zung depression self-rating scale (SDS), the Beck depression self-rating scale (BDI), the depression symptom rapid rating scale (QIDS), the hypomania self-rating scale (HCL-32), the Mood Disorder Questionnaire (MDQ), the young mania scale (YMRS), and the depression screening scale (PHQ 9); more preferably, the depression rating scale is the hamilton depression scale (HAMD).
5. The use according to claim 1, wherein the diagnosis of depression comprises the steps of:

step 1: determining the concentration of 24-hydroxycholesterol in the peripheral blood of the subject;

step 2: comparing the concentration of the 24-hydroxycholesterol measured in the step 1 with a standard concentration; and

and step 3: the subject is judged to be at risk for depression, e.g., if the plasma 24-hydroxycholesterol concentration is greater than 40.85ng/ml, the probability of depression is about 53%.
6. The use of claim 2, wherein predicting and/or judging the therapeutic effect of an antidepressant comprises the steps of:

step 1: measuring the concentration of 24-hydroxycholesterol in the peripheral blood of the subject at different time points of the treatment, and comparing the concentration of 24-hydroxycholesterol in the peripheral blood of the subject measured at the different time points;

preferably, in step 1, the drug therapy is indicated to be ineffective if the concentration of 24-hydroxycholesterol in the peripheral blood of the subject shows an increasing trend as the therapy progresses, and the drug therapy is indicated to be effective if the concentration of 24-hydroxycholesterol in the peripheral blood of the subject shows a decreasing trend as the therapy progresses.
7. A kit for diagnosing depression or for predicting and/or judging the therapeutic effect of an antidepressant, said kit comprising 24-hydroxycholesterol and a depression rating scale; preferably, the depression rating scale is selected from one or more of the hamilton depression scale (HAMD), the montgomery depression scale (MADRS), the Zung depression self-rating scale (SDS), the Beck depression self-rating scale (BDI), the depression symptom rapid rating scale (QIDS), the hypomania self-rating scale (HCL-32), the Mood Disorder Questionnaire (MDQ), the young mania scale (YMRS), and the depression screening scale (PHQ 9); more preferably, the depression rating scale is the hamilton depression scale (HAMD).
8. A kit for diagnosing depression or for predicting and/or judging the therapeutic effect of an antidepressant, said kit comprising a reagent for detecting 24-hydroxycholesterol and a depression assessment scale; preferably, the depression rating scale is selected from one or more of the hamilton depression scale (HAMD), the montgomery depression scale (MADRS), the Zung depression self-rating scale (SDS), the Beck depression self-rating scale (BDI), the depression symptom rapid rating scale (QIDS), the hypomania self-rating scale (HCL-32), the Mood Disorder Questionnaire (MDQ), the young mania scale (YMRS), and the depression screening scale (PHQ 9); more preferably, the depression rating scale is the hamilton depression scale (HAMD).
9. The use according to claim 1 or 2 or the kit according to claim 8, wherein the reagent for detecting 24-hydroxycholesterol is selected from one or more of 24-hydroxycholesterol ligand or an antibody to 24-hydroxycholesterol ligand, an antibody to 24-hydroxycholesterol, a chromogenic reagent, a luminescent marker, a dye, a fluorescent marker, a standard, a basic hydrolysis reagent, a derivatizing reagent, an internal standard and an external standard; preferably, the standard is selected from serum albumin; further preferably, the alkaline hydrolysis reagent is selected from one or more of butyl hydroxy toluene, potassium hydroxide, ethylene diamine tetraacetic acid and ethanol; further preferably, the derivatization reagent is one or more than two selected from N' -diisopropyl carbodiimide, nicotinamide and 4-dimethylaminopyridine; further preferably, said internal standard is selected from D5 deuterium cholesterol and/or D7 deuterium cholesterol; further preferably, the external standard is selected from D5 deuterium cholesterol and/or D7 deuterium cholesterol.
10. The use according to any one of claims 1 to 6 or the kit according to any one of claims 7 to 9, wherein the kit comprises reagents for detecting 27-hydroxycholesterol, serum amyloid P and/or vascular cell adhesion molecules.