CN109549654B

CN109549654B - Common mental disease auxiliary screening kit and method

Info

Publication number: CN109549654B
Application number: CN201710881302.8A
Authority: CN
Inventors: 万春玲; 孙丽雅; 杨旭涵
Original assignee: Shanghai Tianyin Biotechnology Co ltd
Current assignee: Shanghai Tianyin Biotechnology Co ltd
Priority date: 2017-09-26
Filing date: 2017-09-26
Publication date: 2021-05-04
Anticipated expiration: 2037-09-26
Also published as: CN109549654A; WO2019063026A1

Abstract

The invention relates to an auxiliary screening kit and method for common mental diseases. Specifically, the invention relates to a mental disease auxiliary diagnosis kit and a mental disease auxiliary diagnosis method based on niacin skin test. By adopting the reagent combination or the kit, whether the mental disease (including schizophrenia and affective disorder) is suffered or not can be detected or diagnosed in an auxiliary way aiming at specific people, especially male testees, the detection specificity is nearly 100 percent, and the accuracy is very high. Meanwhile, the reagent combination can further provide effective information for distinguishing schizophrenia and affective disorder, and has high accuracy.

Description

Common mental disease auxiliary screening kit and method

Technical Field

The invention relates to the technical field of medical detection, in particular to an auxiliary screening kit and method for common mental diseases.

Background

Schizophrenia is a long-term, debilitating and extremely complex psychotic disorder. Clinically, it is often manifested as a syndrome with various symptoms, involving various disorders such as sensory perception, thinking, emotion and behavior, and an uncoordinated mental activity. The patient is generally aware of the clear and normal intelligence, but some patients suffer from impairment of cognitive function during the course of the disease.

Mood Disorders (MD), also known as Affective Disorders (AD), are a group of diseases caused by various causes with a marked and persistent emotional and mood shift as a major feature. Clinically, the symptoms are mainly manifested as emotional upsets or downsets, accompanied by corresponding changes in cognition and behavior and psychotic symptoms such as hallucination and yao paranoia. According to the phase characteristics of emotions, the emotion recognition method can be divided into three categories: unipolar mania, unipolar depression, and bipolar affective disorder.

Mood disorder and schizophrenia are two different types of mental diseases, but because the mood disorder and schizophrenia are closely related, the symptoms are similar, the clinical misdiagnosis rate is high, the drug treatment response is poor, and the prognosis is not ideal, so that special attention needs to be paid to the identification and the differentiation of the two types of mental diseases during clinical diagnosis. There is currently no objective clinical diagnostic marker for the accurate diagnosis of common psychiatric disorders (such as schizophrenia and affective disorders), which also adds difficulty to the targeted treatment of the disease.

Therefore, there is an urgent need in the art to develop a method for rapid detection and screening of common mental diseases, and distinguishing schizophrenia from affective disorders.

Disclosure of Invention

The invention aims to provide a method for rapidly detecting and screening common mental diseases and distinguishing schizophrenia from affective disorder.

The invention also aims to provide an auxiliary screening kit and method for common mental diseases.

In a first aspect of the invention, there is provided the use of a combination of reagents for the preparation of a kit for (a) detecting whether a subject has a psychotic disorder; and/or (b) for distinguishing between Schizophrenia (SZ) and affective disorder (MD) in a subject, said subject being a human;

wherein the combination of reagents comprises:

(1) a first solution of a 0.08-0.12M solution of a nicotinic acid compound;

(2) a second solution, wherein the second solution is 0.008-0.012M nicotinic acid compound solution;

(3) a third solution of 0.0008-0.0012M nicotinic acid compound; and

(4) optionally, a fourth solution of 0.00008 to 0.00012M nicotinic acid compound.

In another preferred example, the detection comprises auxiliary detection, screening detection, confirmation detection and advanced detection.

In another preferred embodiment, the method for distinguishing whether a subject has Schizophrenia (SZ) and affective disorder (MD) is used for assisting in distinguishing or prompting whether the subject has SZ or MD when the subject is suspected of having SZ and MD.

In another preferred embodiment, the subject is a male.

In another preferred embodiment, the subject is a male and the kit is used for detecting whether the subject has a psychiatric disorder.

In another preferred embodiment, the mental disease comprises SZ and MD.

In another preferred embodiment, the kit comprises instructions for the following criteria:

(a) when the 5min score of the male testee is 0 under the concentration of 0.1M methyl nicotinate solution, the probability that the testee suffers from mental diseases or the onset of the mental diseases is higher than that of the normal population; and/or

(b) When the fraction of 5min of the female testee is 0 under the condition of 0.1M methyl nicotinate solution concentration, the probability that the testee suffers from mental diseases or the onset of the mental diseases is higher than that of the normal population.

In another preferred embodiment, the kit further comprises a timer for setting the timing time.

In another preferred embodiment, the timer may set a timing selected from the group consisting of: 5 minutes, 10 minutes, 15 minutes, 20 minutes, or a combination thereof.

In another preferred embodiment, the niacin compound is selected from the group consisting of: nicotinic acid, methyl nicotinate (AMN), ethyl nicotinate, or combinations thereof.

In another preferred embodiment, the combination of reagents comprises:

(1) a first solution which is a 0.1M solution of methyl nicotinate;

(2) a second solution which is a 0.01M methyl nicotinate solution;

(3) a third solution, said third solution being a 0.001M solution of methyl nicotinate; and

(4) a fourth solution which is a 0.0001M solution of methyl nicotinate.

In another preferred embodiment, the psychiatric disorder is selected from the group consisting of: schizophrenia, affective disorder, or a combination thereof.

In another preferred embodiment, the kit further comprises a label or instructions.

In another preferred embodiment, the label or the instruction label carries judgment criteria, and the judgment criteria are as follows:

(1) when the 5min score is 0 under the concentration of 0.1M methyl nicotinate solution, the probability that the testee suffers from mental diseases or the onset of the mental diseases is higher than that of normal people;

(2) when the tested person is male and the total score is less than 19 or the score is less than 3 at 15min under the condition of 0.1M methyl nicotinate solution concentration, the probability that the tested person suffers from mental diseases or the onset of the mental diseases is higher than that of the normal group; and/or

(3) When the tested person is female and the total score is less than 13 or 0.1M methyl nicotinate solution concentration and the 15min score is less than 2.5, the probability that the tested person suffers from mental diseases or the onset of the mental diseases is higher than that of the normal group.

(4) when the tested person is a suspected SZ and MD patient, if the score of 15min under the concentration of 0.1M methyl nicotinate solution is less than 2.5 and the total score sum is less than 20, the tested person is prompted (or auxiliary diagnosis) to have schizophrenia; and/or

(5) When the tested person is suspected to be a SZ patient and an MD patient, if the 15min score of the 0.1M methyl nicotinate solution concentration is more than or equal to 2.5 and/or the total score sum is more than or equal to 20, the tested person is prompted (or auxiliary diagnosis) to suffer from the affective disorder.

In another preferred example, the total is the total sum of 16 scoring values (4 concentrations x 4 time points), wherein 4 concentrations are 0.0001M, 0.001M, 0.01M and 0.1M and 4 time points are 5 minutes, 10 minutes, 15 minutes and 20 minutes.

In another preferred example, the scoring value (or "score" or "scoring") is performed according to the following criteria: the skin of the subject is stopped after 0.5-2 minutes (e.g., 1 minute) of contact with the first, second, third and fourth solutions, respectively, and then the redness of the skin is scored at 5, 10, 15 and 20 minutes after the stop of contact: the reaction time of no red and swollen is 0 minute, the reaction time of partial red and swollen is 1 minute, the reaction time of complete red and swollen in the contact area is 2 minutes, and the reaction time of red and swollen exceeds the contact area and is 3 minutes.

In another preferred example, the kit further comprises n patches, wherein n is a positive integer greater than or equal to 4.

In another preferred embodiment, the patches are the same size.

In another preferred embodiment, each of said patches has been separately impregnated with said first solution, second solution, third solution, and/or optionally fourth solution.

In another preferred embodiment, the first solution, the second solution, the third solution, and/or the optional fourth solution are located in different containers, respectively.

In a second aspect of the present invention, there is provided a kit for screening for a psychiatric disease, the kit comprising:

(a) a first container, and a first solution in the first container, wherein the first solution is a 0.08-0.12M solution of a nicotinic acid compound;

a second container, and a second solution in the second container, wherein the second solution is 0.008-0.012M nicotinic acid compound solution;

a third container, and a third solution in said third container, said third solution being a 0.0008-0.0012M solution of a nicotinic acid compound;

optionally a fourth container, and a fourth solution in said fourth container, said fourth solution being a 0.00008 to 0.00012M solution of a niacin compound; and

(b) a label or instructions.

In another preferred embodiment, the kit further comprises: (c) a timer.

In another preferred embodiment, the niacin compound is selected from the group consisting of: nicotinic acid, methyl nicotinate, ethyl nicotinate, or combinations thereof.

In another preferred embodiment, the patch is a circular filter paper, preferably a circular filter paper having a diameter of 1.0-1.5cm, more preferably a circular filter paper having a diameter of 1.25-1.30 cm.

In another preferred embodiment, the patch impregnated with the first, second, third or fourth solution is contacted with the skin of the subject, preferably the inner skin of the forearm of the subject, respectively.

In another preferred embodiment, the contact time is 0.5 to 2 minutes, preferably 1 minute.

In another preferred embodiment, the kit further comprises a carrier comprising a test area, wherein the test area comprises at least 4 patches (preferably circular filter papers of 1.25-1.3cm diameter) impregnated with the first, second, third, and fourth solutions, respectively.

In another preferred example, the carrier further comprises a scale.

In another preferred embodiment, the carrier is an adhesive carrier.

In another preferred embodiment, the carrier is externally provided with a seal, which seal is removable and, after removal, allows the test zone of the carrier to be brought into contact with the skin. Preferably, the seal is a removable cover film, more preferably a removable plastic patch.

In another preferred embodiment, the kit (a) is used for detecting whether a subject has a mental disease; and/or (b) for distinguishing whether the subject has schizophrenia and affective disorder.

In a third aspect of the present invention, there is provided a method of detecting a psychiatric disorder, the method comprising the steps of:

(i) providing a nicotinic acid compound solution (e.g., a methyl nicotinate solution), wherein the concentration of said methyl nicotinate solution is from 0.08M to 0.12M; and

(ii) the skin of the testee is contacted with the nicotinic acid compound solution (such as methyl nicotinate solution) for 0.5-2 minutes and then is stopped, and the skin is detected to be inflamed after the 5 th minute after the contact is stopped, and if the skin is not inflamed, the probability that the testee suffers from mental diseases or the onset of the mental diseases is higher than that of the normal population.

In a fourth aspect of the present invention, there is provided a method of detecting a psychiatric disorder, the method comprising the steps of:

a) providing a kit according to the second aspect of the invention; and

b) the skin of the subject is stopped after 0.5-2 minutes of contact with the first, second, third and fourth solutions, respectively, and then the redness of the skin is scored at 5, 10, 15 and 20 minutes after the stop of contact: the non-swelling reaction is 0 minute, the partial swelling reaction is 1 minute, the complete swelling reaction in the contact area is 2 minutes, and the swelling reaction exceeds the contact area by 3 minutes; wherein

When the tested person is male and the total score is less than 19 or the score is less than 3 at 15min under the condition of 0.1M methyl nicotinate solution concentration, the probability that the tested person suffers from mental diseases or the onset of the mental diseases is higher than that of the normal group;

when the tested person is female and the total score is less than 13 or 0.1M methyl nicotinate solution concentration and the 15min score is less than 2.5, the probability that the tested person suffers from mental diseases or the onset of the mental diseases is higher than that of the normal group.

In a fifth aspect of the present invention, there is provided a method of distinguishing whether a subject has schizophrenia from an affective disorder, the method comprising the steps of:

a) providing a kit according to the second aspect of the invention; and

When the tested person is a suspected SZ and MD patient, if the 15min score of the 0.1M AMN concentration is less than 2.5 and the total score sum is less than 20, the probability that the tested person suffers from schizophrenia or the onset of schizophrenia is higher than that of a normal group;

when the tested person is suspected to be a SZ patient and an MD patient, if the 15min score is more than or equal to 2.5 and/or the total score sum is more than or equal to 20 under the concentration of 0.1M AMN, the probability that the tested person suffers from the affective disorder or the onset of the affective disorder is higher than that of a normal group.

It is to be understood that within the scope of the present invention, the above-described features of the present invention and those specifically described below (e.g., in the examples) may be combined with each other to form new or preferred embodiments. Not to be reiterated herein, but to the extent of space.

Drawings

FIG. 1 is a line graph showing the mean distribution of scores of skin tests for skin test of schizophrenia, affective disorders and healthy control population obtained in example 1 of the present invention.

Figure 2 shows a scatter plot of scores for three groups of people with schizophrenia, affective disorder and healthy controls under two score nodes: the two score nodes are respectively '15 min score <2.5 under 0.1M AMN concentration' and 'total score sum < 20'; wherein A is male; b is female.

Figure 3 shows a schematic of the use of a preformed methyl nicotinate patch in which a 1-ruler, 2-test area, 3-dip with a gradient concentration of methyl nicotinate solution master, 4-break point easy tear line.

Detailed Description

The inventor of the invention has conducted extensive and intensive studies, and unexpectedly found for the first time that whether mental diseases (including schizophrenia and affective disorder) are detected or diagnosed in an auxiliary manner by using the reagent combination or the kit of the invention aiming at specific groups of people, especially male testees, the detection specificity is nearly 100%, and the accuracy is very high. Meanwhile, the reagent combination can further provide effective information for distinguishing schizophrenia and affective disorder, and has high accuracy. On this basis, the present inventors have completed the present invention.

Term(s) for

As used herein, the terms "schizophrenia" and "SZ" are used interchangeably to refer to one of the mental diseases. Common symptoms include delusions, hallucinations, disorganized thinking, auditory hallucinations, decreased degree of social involvement and emotional expression, and lack of motivation. Clinical diagnosis is usually determined by the clinician in accordance with the diagnostic criteria of DSM-5 or ICD-10 in combination with clinical experience.

As used herein, the terms "affective disorder" and "MD" are used interchangeably to refer to a class of mental disorders characterized primarily by marked and persistent emotional and mood changes due to a variety of causes. Clinically, the symptoms are mainly manifested as emotional upsets or downsets, accompanied by corresponding changes in cognition and behavior and psychotic symptoms such as hallucination and yao paranoia. According to the phase characteristics of emotions, the emotion recognition method can be divided into three categories: unipolar mania, unipolar depression, and bipolar affective disorder.

As used herein, the term "niacin compound" includes the following compounds: nicotinic acid, methyl nicotinate, ethyl nicotinate, or combinations thereof.

Swelling due to nicotinic acid

The nicotinic acid erythroma response is a response of epidermal vasodilation and cutaneous flushing regulated by Hydroxy-carboxylic acid receptor (HCA 2). Studies in caucasian populations have found that this response tends to be significantly attenuated in schizophrenic populations relative to affective and healthy populations.

The invention adopts a semi-quantitative water-soluble methyl nicotinate (AMN) patch and a scoring method to research different expressions of niacin swelling reaction in Han population in two common mental diseases (schizophrenia and affective disorder) and normal population, and aims to find an effective method which can screen a niacin insensitive subgroup of common mental disease patients from a normal population and distinguish the patients with schizophrenia and affective disorder so as to reduce misdiagnosis rate.

Detection method

As used herein, the auxiliary detection method of the present invention comprises: the skin of the subject is stopped after 0.5-2 minutes (e.g., 1 minute) of contact with the first, second, third and fourth solutions of the first aspect of the invention, respectively, and then 5 minutes, 10 minutes, 15 minutes and 20 minutes after the stop of contact, the redness and swelling of the skin is scored: the non-swelling reaction is 0 minute, the partial swelling reaction is 1 minute, the complete swelling reaction in the contact area is 2 minutes, and the swelling reaction exceeds the contact area by 3 minutes; and auxiliary detection is carried out according to the scoring condition and the judgment standard of the invention.

In another preferred embodiment, the method for auxiliary detection of mental diseases comprises the following steps:

(i) providing a methyl nicotinate solution, wherein the concentration of the methyl nicotinate solution is 0.08-0.12M; and (ii) contacting the skin of the subject with the nicotinic acid compound solution (such as methyl nicotinate solution) for 0.5-2 minutes, then stopping the contact, and detecting the redness and swelling of the skin after the 5 th minute after the contact is stopped, wherein if the redness and swelling do not exist, the probability that the subject suffers from the mental disease or the mental disease is higher than that of the normal population.

Judgment criteria

(1) When the 5min score of the 0.1M methyl nicotinate solution is 0, the tested person is prompted to have mental diseases or the incidence rate of the mental diseases is higher than that of the normal group;

(2) when the tested person is male and the total score is less than 19 or the score is less than 3 at 15min under the concentration of 0.1M methyl nicotinate solution, the tested person is prompted to have mental diseases or the incidence rate of the mental diseases is higher than that of the normal group;

(3) when the tested person is female and the total score is less than 13 or 0.1M methyl nicotinate solution concentration and the 15min score is less than 2.5, the tested person is prompted to have mental diseases or the incidence rate of the mental diseases is higher than that of the normal group;

(4) when the tested person is a suspected SZ and MD patient, if the 15min score of the 0.1M AMN concentration is less than 2.5 and the total score sum is less than 20, the probability that the tested person suffers from schizophrenia or the onset of schizophrenia is higher than that of a normal group;

(5) when the tested person is suspected to be a SZ patient and an MD patient, if the 15min score is more than or equal to 2.5 and/or the total score sum is more than or equal to 20 under the concentration of 0.1M AMN, the probability that the tested person suffers from the affective disorder or the morbidity of the affective disorder is higher than that of a normal population.

The main advantages of the invention include:

1. the reagent combination can provide effective information for distinguishing schizophrenia and affective disorder, and has strong specificity and high accuracy.

2. For a specific population, particularly male testees, the method can accurately diagnose whether the patients suffer from mental diseases (including schizophrenia and affective disorder), has the specificity of nearly 100 percent, and has very high accuracy.

3. The method adopts the in vitro adhesion of the methyl nicotinate solution patch, diagnoses common mental diseases such as schizophrenia and the like through the skin swelling reaction, and has the advantages of convenient operation, no wound and the like.

The invention will be further illustrated with reference to the following specific examples. It should be understood that these examples are for illustrative purposes only and are not intended to limit the scope of the present invention. Experimental procedures without specific conditions noted in the following examples, generally followed by conventional conditions, such as Sambrook et al, molecular cloning: the conditions described in the Laboratory Manual (New York: Cold Spring Harbor Laboratory Press,1989), or according to the manufacturer's recommendations. Unless otherwise indicated, percentages and parts are by weight.

Unless otherwise specified, the materials and reagents used in the examples of the present invention are commercially available products.

Example 1 nicotinic acid erythroma response differential in schizophrenia, affective disorders and normal controls

1. Sample collection

163 patients with schizophrenia, 63 patients with affective disorders and 63 normal controls diagnosed by ICD-10 were collected. All the individuals in the group have no body diseases such as diabetes, malignant tumor, fever, inflammation and the like, and all the female individuals are not in the gestational period. The study was reviewed by ethical committee of the fourth national hospital in the city of turnip lake, the protocol of the experiment was in accordance with ethical principles, and all members of the group were officially informed in writing.

2. Reagent preparation and skin test scoring

1) Four concentrations (0.1, 0.01, 0.001 and 0.0001M) of methyl hydrochloride solution (AMN, C7H7NO2, 99%, Sigma-Aldrich, st. louis, MO, US) were freshly prepared.

2) A circular piece of filter paper with a diameter of 1.29cm was used as a patch and soaked in four concentrations of AMN solution.

3) A transparent ruler is attached to the inside of the forearm of the subject to locate the patch.

4) The 4 patches soaked with different concentrations of AMN were sequentially attached to the inner skin of the forearm of the subject, and the patches were removed after one minute.

5) Photographs were taken perpendicular to the forearm medial patch position after 5 minutes, 10 minutes, 15 minutes and 20 minutes, respectively.

6) And (3) scoring according to the red and swollen condition of the skin of the patch part of the testee in the picture by adopting a 4-score scoring method: 0-no red and swollen reaction, 1-partial red and swollen reaction, 2-complete red and swollen reaction in the range of the patch, and 3-red and swollen reaction beyond the range of the patch. Two trained researchers scored independently.

3. Data analysis

The scoring values for both investigators were averaged as the final scoring value. Each subject had 16 score values (4 concentrations x 4 time points), a sum of 4 concentrations, a sum of 4 time points, and a total sum of all 16 score values. BMI, education, nicotine dependence (FTND) as covariates, comparisons were made between different disease groups and different sexes.

As can be seen in FIG. 1, the swelling response to nicotinic acid is shown differently in schizophrenia, affective disorders and normal controls. The score of the schizophrenic group was generally lower than that of the normal control group, indicating that schizophrenic patients were insensitive to methyl nicotinate, slow in response and low in response (figure 1). The affective disorder group showed similar behavior to the schizophrenic group at the lowest concentration of methylnicotinate (0.0001M) or the shortest time (5min), but the swelling response approached that of the normal control group with the increase of methylnicotinate concentration and the time, and exceeded the swelling response of the normal control group even at 20min with 0.1M methylnicotinate. This indicates that the skin redness response caused by methyl nicotinate is delayed but not reduced in patients with affective disorders.

Example 2 screening for common psychiatric disorders

The results of the experiment show that at high concentrations of methylnicotinate, redness and swelling of the skin rapidly occurred in the normal control group, while the skin reactions were retarded in the schizophrenia group and the affective disorder group. Therefore, niacin skin swelling reaction is used for assisting in screening patients with common mental diseases.

1. Taking the standard of 0 for 5min under 0.1M AMN concentration (also called index or node), if the condition is met, the nicotinic acid insensitivity is judged (namely the common mental disease or the mental disease has high possibility)

The marker is used as a clinical auxiliary screening marker of a population with common mental diseases (including schizophrenia and affective disorder), the sensitivity is 26.22%, and the specificity is 96.83% (Table 1). As can be seen from Table 1, in males, the specificity of the index as a clinical auxiliary screening marker can reach 100%, and the sensitivity is 26.98%; specificity and sensitivity were 96.23% and 25.25% in women, respectively.

Table 1 screening of common mental diseases with the node "0 is scored at 0.1M AMN concentration for 5min ═ 0

	For male	Woman	Sum of
				Sensitivity of the composition	26.98％	25.25％	26.22％
Specificity of	100.00％	96.23％	96.83％

2. The common mental diseases were screened with both 15min score and total score (total score) at 0.1M AMN concentration. The total score sum (total score) refers to the total sum of 16 score values (4 concentrations × 4 time points). According to the invention, different thresholds are respectively adopted as screening standards in males and females according to different sexes.

In the male population, the patients meeting the criteria of 'total score <19 or 0.1M 15min < 3' are judged to be insensitive to nicotinic acid (namely, the patients have common mental diseases or have high possibility of the occurrence of the mental diseases), and the specificity of screening the common mental diseases reaches 90.00 percent and the sensitivity reaches 62.20 percent according to the criteria (Table 2).

In the female population, the patients meeting the criteria of "total score <13 or 0.1M 15min < 2.5" are judged to be insensitive to nicotinic acid (namely, the patients have common mental diseases or have high possibility of developing the mental diseases), and the specificity of screening the common mental diseases reaches 79.25 percent and the sensitivity reaches 49.49 percent according to the criteria (Table 2).

TABLE 2 screening of commonly occurring psychiatric disorders with two conditions of "15 min score at 0.1M AMN concentration and Total score sum

Sex	Screening conditions judged insensitive	Sensitivity of the composition	Specificity of
				For male	Total score<19 or 0.1M 15min<3	62.20％	90.00％
Woman	Total score<13 or 0.1M 15min<2.5	49.49％	79.25％

Example 3 screening for schizophrenia and affective disorders

In single factor analysis, bias η²Are commonly used to assess the impact of independent variables on disease grouping. 0.1M AMN 15min score between schizophrenic and affective groups²Max (0.045), the sum of all scores skews η between the schizophrenic group and the normal control group²The maximum (0.115) represents that the two indexes can better distinguish different disease groups. The invention takes 0.1M AMN 15min<2.5 and total score sum<20' is the standard, and the person who meets the condition considers that the nicotinic acid is insensitive (namely, the person has common schizophrenia or the possibility of the schizophrenia is high)

The results indicate that 73% of nicotinic acid-insensitive subjects were accurately diagnosed as schizophrenia under this criteria. Using this index, patients with schizophrenia can be better screened and patients with schizophrenia and affective disorders can be distinguished (Table 3). Nodes of 15min score <2.5 and total score <20 at 0.1M AMN concentration can distinguish patients with schizophrenia and nicotinic acid insensitivity to affective disorder.

Table 3 node-assisted screening of schizophrenic patients with a 0.1M AMN 15min score <2.5 and a total score sum <20 and differentiation between schizophrenia and affective disorders

	SZ and HC	SZ and MD	SZ and HC + MD
				Sensitivity of the composition	31.45％	31.45％	31.45％
Specificity of	83.33％	87.30％	85.37％

Considering the influence of gender on the niacin skin response, the subjects were regrouped according to gender and scored as shown in fig. 2. As can be seen from FIG. 2, this index shows very good specificity in males. In women, sensitivity is 42.03%.

Example 4 Niacin skin test screening of common psychiatric disorders Niacin insensitive people kit

The product is a prefabricated methyl nicotinate patch.

The preformed methyl nicotinate patch is shown in figure 3. The adhesive carrier is divided into two parts of a scale (1) and a test area (2), wherein the test area is provided with 4 circular filter paper sheets (3) with the diameter of 1.29cm, and the circular filter paper sheets are sequentially soaked with 0.1M, 0.01M, 0.001M and 0.0001M methyl nicotinate solution. The adhesive carrier is covered by a plastic film, the plastic film is removed, the whole adhesive carrier is flatly attached to the inner side of the upper arm, and the low-concentration (0.0001M) methyl nicotinate patch is close to the wrist. After attaching for 1 minute, tearing off the test area along the dotted line (4), taking pictures at 5min, 10min, 15min and 20min respectively, and uploading the pictures to a remote end such as a mobile phone. The testee is required to be perpendicular to the arm as much as possible when taking a picture, and the scale part is taken together. The subjects were scored for redness and swelling of the arm (table 4).

TABLE 4 points table

Note: AMN is methyl nicotinate solution.

All documents referred to herein are incorporated by reference into this application as if each were individually incorporated by reference. Furthermore, it should be understood that various changes and modifications of the present invention can be made by those skilled in the art after reading the above teachings of the present invention, and these equivalents also fall within the scope of the present invention as defined by the appended claims.

Claims

1. Use of a combination of reagents for the preparation of a kit for detecting whether a subject has a psychiatric disorder, wherein the subject is a human;

wherein the combination of reagents comprises:

(1) a first solution of a 0.08-0.12M solution of a nicotinic acid compound;

(3) a third solution of 0.0008-0.0012M nicotinic acid compound; and

(4) optionally a fourth solution of 0.00008 to 0.00012M of a niacin compound; the psychiatric disorder is an affective disorder selected from the group consisting of: monophasic mania, monophasic depression, bipolar disorder, or a combination thereof.

2. Use of a combination of reagents for the preparation of a kit for distinguishing between Schizophrenia (SZ) and affective disorders (MD) in a subject, said subject being a human;

wherein the combination of reagents comprises:

(1) a first solution of a 0.08-0.12M solution of a nicotinic acid compound;

(3) a third solution of 0.0008-0.0012M nicotinic acid compound; and

(4) optionally a fourth solution of 0.00008 to 0.00012M of a niacin compound solution, wherein the affective disorder is selected from the group consisting of: monophasic mania, bipolar disorder, or a combination thereof.

3. The use of a combination of agents according to claim 2 for distinguishing between Schizophrenia (SZ) and affective disorders (MD) in a subject is when the subject is suspected of having SZ and MD, for aiding in the distinction or to indicate whether the subject has SZ or MD.

4. Use of a combination of agents according to claim 1 or 2, wherein the subject is male.

5. Use of a combination of reagents according to claim 1 or 2, wherein in the kit, instructions for the following criteria are included:

6. Use of a combination of reagents according to claim 1 or 2, wherein the kit further comprises a timer for setting the timing time.

7. Use of a combination of reagents according to claim 6, wherein the timer is settable for a time selected from the group consisting of: 5 minutes, 10 minutes, 15 minutes, 20 minutes, or a combination thereof.

8. Use of a combination of agents according to claim 1 or 2, wherein the niacin compound is selected from the group consisting of: nicotinic acid, methyl nicotinate, ethyl nicotinate, or combinations thereof.

9. Use of a combination of agents according to claim 1 or 2, wherein the combination of agents comprises:

(1) a first solution which is a 0.1M solution of methyl nicotinate;

(2) a second solution which is a 0.01M methyl nicotinate solution;

(4) a fourth solution which is a 0.0001M solution of methyl nicotinate.

10. Use of a combination of reagents according to claim 1 or 2, wherein the kit further comprises instructions for the following criteria:

(2) when the tested person is male and the total score is less than 19 or the score is less than 3 at 15min under the concentration of 0.1M methyl nicotinate solution, the tested person is prompted to have mental diseases or the incidence rate of the mental diseases is higher than that of the normal group; and/or

(3) When the tested person is female and the total score is less than 13 or the 15min score of 0.1M methyl nicotinate solution concentration is less than 2.5, the tested person is suggested to have mental diseases or the probability of the onset of the mental diseases is higher than that of the normal population.

11. Use of a combination of reagents according to claim 1 or 2, wherein the kit further comprises instructions for the following criteria:

(4) when the tested person is a suspected SZ and MD patient, if the score of 15min under the concentration of 0.1M methyl nicotinate solution is less than 2.5 and the total score sum is less than 20, the tested person is prompted to have schizophrenia; and/or

(5) And when the tested person is a suspected SZ and MD patient, if the 15min score of the 0.1M methyl nicotinate solution concentration is more than or equal to 2.5 and/or the total score sum is more than or equal to 20, the tested person is prompted to suffer from the affective disorder.

12. Use of a combination of agents according to claim 1 or 2, wherein the total is the total sum of 16 scoring values (4 concentrations x 4 time points), wherein 4 concentrations are 0.0001M, 0.001M, 0.01M and 0.1M and 4 time points are 5 minutes, 10 minutes, 15 minutes and 20 minutes.

13. The use of the combination of reagents according to claim 1 or 2, wherein the kit further comprises n patches, n being a positive integer no less than 4.

14. Use of a combination of reagents according to claim 13, wherein each patch has been separately impregnated with the first solution, the second solution, the third solution, and/or optionally the fourth solution.