WO2013080917A1 - Procédé d'évaluation objective de la schizophrénie - Google Patents

Procédé d'évaluation objective de la schizophrénie Download PDF

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WO2013080917A1
WO2013080917A1 PCT/JP2012/080476 JP2012080476W WO2013080917A1 WO 2013080917 A1 WO2013080917 A1 WO 2013080917A1 JP 2012080476 W JP2012080476 W JP 2012080476W WO 2013080917 A1 WO2013080917 A1 WO 2013080917A1
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schizophrenia
marker
acid
test
administration
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PCT/JP2012/080476
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English (en)
Japanese (ja)
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岩本　和也
清登 笠井
進介 小池
美紀 文東
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国立大学法人東京大学
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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6893—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to diseases not provided for elsewhere
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/70—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving creatine or creatinine
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2500/00—Screening for compounds of potential therapeutic value
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/52—Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis

Definitions

  • the present invention relates to a test method for objectively evaluating the risk of onset of schizophrenia and the presence or absence of onset.
  • Schizophrenia is a typical mental illness formerly called schizophrenia, and the prevalence is said to be about 1%. Schizophrenia is generally characterized by positive symptoms such as hallucinations and delusions and negative symptoms such as reduced motivation and emotional dullness.
  • Non-Patent Document 1 lipid profile analysis before and after treatment of schizophrenia with three commonly used atypical ⁇ antipsychotics was reported, and the effects of those drugs were reported.
  • Non-Patent Document 1 the literature does not compare healthy subjects with schizophrenic patients.
  • Non-patent Document 2 profiles of 13 tryptophan metabolites were analyzed in healthy subjects and patients with schizophrenia in the first episode, and similarly, before and after the first episode treatment with antipsychotic drugs, It has been reported that the ratio between some metabolites and tryptophan is changed in patients (Non-patent Document 2).
  • peripheral blood mononuclear cells from patients with schizophrenia and healthy individuals in the first episode are subjected to proteome analysis under stimulation and non-stimulation, and 18 kinds of proteins including glycolytic enzymes Has been reported to be usable as a marker for schizophrenia (Non-patent Document 3).
  • metabolomic analysis using GC-TOFMS etc. is performed on psychiatric patients including schizophrenia and healthy subjects, and six lipid clusters mainly containing saturated triglycerides and two other low molecular clusters (branched chain amino acids).
  • lipid clusters mainly containing saturated triglycerides and two other low molecular clusters (branched chain amino acids) has been suggested to be associated with schizophrenia (clusters containing proline, glutamic acid, etc.) (Non-patent Document 4).
  • a compound selected from betaine, creatine, glutamic acid, gluconic acid, pelargonic acid, imidazoleacetic acid, perillic acid, and cyclohexylamine can be used as a marker for schizophrenia.
  • An object of the present invention is to provide a method for accurately examining the risk of developing schizophrenia and the presence or absence of the onset.
  • the present inventors correlate a compound selected from betaine, creatine, glutamic acid, gluconic acid, pelargonic acid, imidazoleacetic acid, perillic acid, and cyclohexylamine with schizophrenia. I found out. And it discovered that the onset risk of schizophrenia and the presence or absence of onset could be correctly test
  • the present invention includes the following aspects: [1] A method for testing schizophrenia, Measuring a marker of schizophrenia in a test sample collected from a subject, and examining schizophrenia based on a result of the measurement, The method wherein the marker is one or more compounds selected from the group consisting of betaine, creatine, glutamic acid, gluconic acid, pelargonic acid, imidazole acetic acid, perillic acid, and cyclohexylamine. [2] Said method wherein at least betaine is measured. [3] The method, wherein at least betaine, glutamic acid, and pelargonic acid are measured.
  • a method for screening a model animal for schizophrenia comprising: Testing the subject animal for schizophrenia using the method, and determining whether the subject animal is a model animal for schizophrenia based on the results of the test.
  • a method of screening for a therapeutic drug for schizophrenia Administering a candidate compound for the treatment of schizophrenia to a test animal exhibiting the pathology of schizophrenia, Measuring a marker of schizophrenia in a test sample collected from the test animal not administered the candidate compound; Measuring the marker in a test sample collected after administration of the candidate compound from the test animal, and determining whether the candidate compound is a therapeutic drug for schizophrenia based on a result of the measurement.
  • the marker is one or more compounds selected from the group consisting of betaine, creatine, glutamic acid, gluconic acid, pelargonic acid, imidazole acetic acid, perillic acid, and cyclohexylamine.
  • a method for determining the efficacy of a therapeutic drug for schizophrenia in a test individual Measuring a marker of schizophrenia in a test sample collected from a test individual exhibiting the pathology of schizophrenia before administration of a therapeutic drug for schizophrenia, Measuring the marker in a test sample collected after administration of the therapeutic agent from the test individual, and determining the efficacy of the therapeutic agent in the test individual based on the result of the measurement,
  • the method wherein the marker is one or more compounds selected from the group consisting of betaine, creatine, glutamic acid, gluconic acid, pelargonic acid, imidazole acetic acid, perillic acid, and cyclohexylamine.
  • shaft shows the relative area value of a metabolite.
  • shaft shows the relative area value of a metabolite.
  • a — 0039 perillic acid
  • C — 0011 cyclohexylamine.
  • shaft shows the relative area value of a metabolite.
  • the vertical axis represents the relative area value of betaine.
  • the present invention relates to schizophrenia, comprising measuring a marker for schizophrenia (hereinafter also referred to as “the marker of the present invention” or “marker”), and examining schizophrenia based on the measurement result. Is provided (hereinafter also referred to as “inspection method of the present invention” or “method of the present invention”).
  • the “test” includes a test for the risk of developing schizophrenia, a test for the presence of schizophrenia, and a test for the severity of schizophrenia. That is, in the present invention, a marker in a test sample collected from a subject is measured, and the measurement results are used to determine the risk of developing schizophrenia and the onset of schizophrenia in the subject from which the test sample was collected. Correlate with presence and / or severity of schizophrenia.
  • schizophrenia is not particularly limited.
  • the schizophrenia may be any type of schizophrenia: delusion type, dismantling type (destructive type), tension type, indistinguishable type, remnant type, or simple type.
  • schizophrenia may be early schizophrenia, acute schizophrenia, or chronic schizophrenia.
  • the schizophrenia may be a first episode psychosis, specifically, a first episode schizophrenia.
  • First episode refers to the first episode.
  • the subject may be a subject (human subject) or a subject animal (animal subject).
  • a subject animal animal
  • the age of the subject is not particularly limited.
  • the subject may be a young subject, specifically, a subject under 30 years old.
  • the marker measured in the present invention is one or more compounds selected from the group consisting of betaine, creatine, glutamic acid, gluconic acid, pelargonic acid, imidazoleacetic acid, perillic acid, and cyclohexylamine.
  • betaine means trimethylglycine.
  • at least betaine is preferably measured.
  • at least betaine, pelargonic acid, and cyclohexylamine are preferably measured, and at least glutamic acid, betaine, and pelargonic acid are also preferably measured.
  • the marker selected from the above and other markers may be combined and measured.
  • the marker selected from the above and a known schizophrenia marker may be combined and measured.
  • “measuring the marker” means quantifying the concentration of the marker in the test sample or measuring a value reflecting the concentration of the marker in the test sample.
  • the quantitative value of the marker concentration or the value reflecting the marker concentration obtained by measuring the marker is also referred to as a “marker measurement value”.
  • “marker measurement” is also referred to as “marker quantification”.
  • the “value reflecting the marker concentration” is not particularly limited as long as it correlates with the marker concentration and can be used for quantitatively comparing the marker concentration between test samples. That is, the marker concentration itself may not be acquired as long as the marker concentration can be quantitatively compared. Examples of the value that reflects the marker concentration include raw data measured to calculate the marker concentration and data obtained by processing the raw data.
  • Such data include data obtained by standardizing peak areas in chromatograms obtained by CE-TOFMS, absorbance increase / decrease values in colorimetric determination, and the like.
  • the value reflecting the marker concentration may be, for example, a relative marker concentration with respect to an arbitrary reference.
  • the test sample to be analyzed in the present invention is blood isolated from a subject or obtained by processing it.
  • examples of those obtained by processing blood include serum and plasma. Serum or plasma can be obtained, for example, by standing or centrifuging blood.
  • blood, serum, and plasma are also collectively referred to as “blood sample”.
  • the blood sample may be used for the measurement of the marker as it is, or may be used for the measurement of the marker after appropriate pretreatment if necessary.
  • the pretreatment include termination of an enzyme reaction in a blood sample, removal of a fat-soluble substance, and removal of a protein. These pretreatments may be performed by a known method, for example.
  • the test sample may be diluted or concentrated as appropriate.
  • the method for measuring the marker is not particularly limited, and for example, the marker can be measured by a known method. When measuring a plurality of markers, each marker may be measured simultaneously or separately.
  • a marker can be measured by selecting and using a quantitative method according to the marker of interest.
  • a marker can also be measured using a commercially available quantification kit corresponding to the marker to be measured.
  • the marker can be measured by using capillary electrophoresis, liquid chromatography, gas chromatography, mass spectrometer, etc. alone or in appropriate combination. These measurement techniques are particularly suitable when measuring a plurality of markers together.
  • a measurement method suitable for a marker having high ionicity measurement by capillary electrophoresis-mass spectrometer can be mentioned.
  • the marker can be measured by a capillary electrophoresis-time-of-flight mass spectrometer (CE-TOFMS).
  • CE-TOFMS capillary electrophoresis-time-of-flight mass spectrometer
  • Measured values of markers obtained by measuring markers are classified into normal values and abnormal values based on a predetermined threshold. If the measurement value of the marker is within the normal range as a result of the measurement, the possibility of developing schizophrenia and / or the possibility of developing schizophrenia (collectively, the possibility of schizophrenia) If the measured value of the marker is within the abnormal value range, it can be determined that the possibility of schizophrenia is high.
  • “normal value” refers to a range where the possibility of schizophrenia is low for a measurement value of a certain marker, and “abnormal value” is a high possibility of schizophrenia for a measurement value of a certain marker. A range. Note that “determining that the possibility of schizophrenia is low” for a subject includes determining that the subject does not suffer from schizophrenia. Further, “determining that the possibility of schizophrenia is high” for a subject includes determining that the subject is suffering from schizophrenia.
  • the measurement value of a certain marker being included in the normal value range is also referred to as “negative” as the determination result of the marker.
  • a measurement value of a certain marker being included in the range of abnormal values is also referred to as “positive” as a result of the marker determination.
  • the marker when the marker is selected from creatine, glutamic acid, and gluconic acid, it may be determined that the possibility of schizophrenia is high when the measured value of the marker is equal to or greater than a threshold value. Moreover, you may determine with the possibility that a schizophrenia is so high that the measured value of a marker is high. Moreover, you may determine with the severity of schizophrenia being so high that the measured value of a marker is high. In this case, a value greater than or equal to the threshold value is an abnormal value, and a value less than the threshold value is a normal value.
  • the marker is selected from betaine, pelargonic acid, imidazoleacetic acid, perillic acid, and cyclohexylamine
  • a threshold value Good.
  • a value below the threshold is an abnormal value
  • a value exceeding the threshold is a normal value.
  • the threshold value may be appropriately determined by those skilled in the art according to various conditions such as the purpose of the examination for schizophrenia, the type, sex, and age of the subject, the type of test sample, and the type of marker measurement value.
  • the method for determining the threshold is not particularly limited, and for example, the threshold can be determined according to a known method.
  • the threshold may be determined based solely on the results of measuring markers in subjects suffering from schizophrenia (case subjects; case subjects), and subjects not suffering from schizophrenia (control subjects) It may be determined based only on the result of measuring the marker with the body (control subject), or may be determined based on both the result of measuring the marker with the case subject and the control subject. The threshold is preferably determined based on both the result of measuring the marker in the case subject and the control subject.
  • Case subjects may or may not have other illnesses as long as they are suffering from schizophrenia, but other than schizophrenia, diseases that correlate with the measured marker Preferably it is not affected.
  • the control subject may or may not be affected by any other disease as long as he / she does not suffer from schizophrenia, but is not affected by a disease that correlates with the marker being measured. preferable.
  • the threshold value when the threshold value is determined based only on the result of measuring the marker in the control subject, the range from the upper limit to the lower limit of the marker concentration measured in multiple individuals of the control subject is the normal value range.
  • the threshold value may be determined such that the average value ⁇ standard deviation range of the marker concentration measured in a plurality of individuals of the control subject is within the normal value range.
  • the threshold value in the distribution of marker measurement values measured by a plurality of individuals of the control subject, the threshold value may be determined so that a predetermined percentage of the control subject is included in the range of normal values.
  • the predetermined ratio may be, for example, 70% or more, preferably 80% or more, more preferably 90% or more, still more preferably 95% or more, and particularly preferably 100%.
  • the threshold value is determined based only on the result of measuring the marker in the case subject.
  • the threshold value is set in consideration thereof.
  • the normal subject range includes a predetermined percentage of the control subject and the abnormal subject range.
  • the threshold may be determined so that case subjects are included in a predetermined ratio. Specifically, for example, in the case of a marker having a high possibility of schizophrenia when the measured value is equal to or greater than a threshold value, the case subjects are included in a predetermined ratio above the threshold value, and the control subject is less than the threshold value.
  • the threshold value can be determined so as to be included in a predetermined ratio.
  • case subjects are included in a predetermined ratio below the threshold, and the control subject is
  • the threshold value can be determined so that a predetermined ratio is included in the range exceeding the threshold value.
  • both the ratio of case subjects exhibiting abnormal values and the ratio of control subjects exhibiting normal values are high.
  • Each of these ratios may be, for example, 70% or more, preferably 80% or more, more preferably 90% or more, still more preferably 95% or more, and particularly preferably 100%.
  • the higher these ratios the higher the specificity and sensitivity.
  • Both specificity and sensitivity are preferably higher.
  • Specificity and sensitivity may be, for example, 70% or more, preferably 80% or more, more preferably 90% or more, still more preferably 95% or more, and particularly preferably 100%.
  • Specificity means the rate of negativeness in a control subject, the higher the specificity, the lower the false positive rate.
  • Sensitivity means the rate of positive in case subjects, and the higher the sensitivity, the lower the false negative rate.
  • a threshold value that increases either specificity or sensitivity may be set according to the purpose of the schizophrenia test or the like. For example, if the purpose is to determine that the test result is positive, the threshold may be set so that the specificity is high. Alternatively, for example, if the purpose is to exclude schizophrenia when the test result is negative, the threshold value may be set so that the sensitivity is increased.
  • the threshold value may be determined using commercially available software.
  • statistical analysis software may be used to determine a threshold value that allows statistically most appropriate discrimination between control subjects and case subjects.
  • JMP which is statistical analysis software of SAS.
  • the threshold value may be appropriately determined by those skilled in the art. Specifically, for example, the normal value range of creatine concentration in human serum is 0.1 to 1.2 mg / dl for males and 0.2 to 1.6 mg for females. May be / dl.
  • schizophrenia When schizophrenia is tested by combining multiple markers, it may be determined that schizophrenia is likely if at least one marker is positive, and schizophrenia only if all markers are positive It may be determined that there is a high possibility. Moreover, you may determine with the possibility of schizophrenia being so high that there are many markers determined to be positive. Moreover, you may judge that the severity of schizophrenia is so high that there are many markers determined to be positive.
  • a marker whose threshold is set so as to increase sensitivity is used, and a subject whose test result is negative is integrated. It can be excluded from the test subject as having a very low possibility of ataxia, and the test can be continued using another marker only for a subject having a positive determination result.
  • schizophrenia may be tested by combining a test for schizophrenia using the marker of the present invention with another test for schizophrenia.
  • Other schizophrenia tests include schizophrenia tests using interviews and questionnaires, schizophrenia tests, and genes, proteins, and compounds that correlate with schizophrenia.
  • ⁇ Screening method of model animal for schizophrenia> By using the marker of the present invention, a model animal for schizophrenia can be screened.
  • the present invention is a method of screening a model animal for schizophrenia, Inspecting schizophrenia of a test animal using the test method of the present invention, and determining whether the test animal is a model animal of schizophrenia based on the result of the test (hereinafter, , Also referred to as “model animal screening method of the present invention”).
  • the test animal is integrated when it is determined that the possibility of schizophrenia is high as a result of examining the test animal for schizophrenia using the test method of the present invention. It can be determined that it is a model animal for ataxia.
  • the therapeutic agent for schizophrenia can be screened.
  • the “therapeutic agent” referred to here includes a prophylactic agent.
  • the present invention is a method of screening for a therapeutic agent for schizophrenia, Administering a candidate compound for the treatment of schizophrenia to a test animal exhibiting the pathology of schizophrenia, Measuring a marker of schizophrenia in a test sample collected from the test animal not administered the candidate compound; Measuring the marker in a test sample collected after administration of the candidate compound from the test animal, and determining whether the candidate compound is a therapeutic drug for schizophrenia based on a result of the measurement. (Hereinafter also referred to as “the screening method of the therapeutic agent of the present invention”).
  • the candidate compound when it is determined as a result of measurement that schizophrenia has been improved by administration of a candidate compound, the candidate compound is determined to be a therapeutic agent for schizophrenia. it can.
  • test animal showing the pathology of schizophrenia is not particularly limited as long as it is a test animal and has been determined to have a high possibility of schizophrenia.
  • the test animal used may be one that has been determined to have a high possibility of schizophrenia by the test method of the present invention, or one that has been determined to have a high possibility of schizophrenia by a known method. It may be determined that the possibility of schizophrenia is high by a combination thereof.
  • the test animal showing the pathology of schizophrenia includes not only those already showing the pathology of schizophrenia, but also the pathology of schizophrenia in the future. Those that are highly likely to indicate are also included.
  • test animal used does not show the pathological condition of schizophrenia before the onset of schizophrenia, but according to the test method of the present invention, the possibility of schizophrenia (here, schizophrenia develops). May be determined to be high).
  • the test animal used may be a schizophrenia model animal as described above.
  • the “candidate compound for the treatment of schizophrenia” may be any substance.
  • “After administration of candidate compound” may be appropriately set according to the type of compound, the dose of compound, the type of test animal, and the like. “After administration of candidate compound” may be, for example, any time point from 1 minute to 24 hours after administration of the candidate compound, and any time point after 10 minutes to 12 hours. It's okay.
  • the schizophrenia has been improved by administration of the candidate compound means that the possibility of schizophrenia is lower after administration of the candidate compound or schizophrenia than before administration of the candidate compound. It means that the severity of is low. Whether schizophrenia has been improved by administration of the candidate compound can be determined by comparing the measured values of the markers before and after administration of the candidate compound.
  • the measured value of the marker approaches the normal value range by administration of the candidate compound, it may be determined that schizophrenia has been improved by administration of the candidate compound.
  • a marker determined to be positive before administration of a candidate compound is determined to be negative after administration, it may be determined that schizophrenia has been improved by administration of the candidate compound.
  • the measured value of at least one marker approaches the normal value range by administration of the candidate compound, it is determined that schizophrenia has been improved by administration of the candidate compound.
  • the measured values of all the markers approach the normal value range by administration of the candidate compound, it may be determined that schizophrenia has been improved by administration of the candidate compound.
  • the number of markers determined to be negative is increased by administration of a candidate compound, it may be determined that schizophrenia has been improved by administration of the candidate compound.
  • an individual from whom a test sample for measuring a marker before administration of a candidate compound is collected and a test sample for measuring a marker after administration of the candidate compound are collected.
  • the individual may or may not be the same individual. That is, “a test sample collected from a test animal that has not been administered a candidate compound” may be collected from an individual to which a candidate compound is administered before the administration of the candidate compound. It may be collected from another individual who has not been administered the candidate compound.
  • the “therapeutic agent” referred to here includes a prophylactic agent.
  • the present invention is a method for determining the efficacy of a therapeutic drug for schizophrenia in a test individual, Measuring a marker of schizophrenia in a test sample collected from a test individual exhibiting the pathology of schizophrenia before administration of a therapeutic drug for schizophrenia, Measuring the marker in a test sample collected after administration of the therapeutic agent from the test individual, and determining the efficacy of the therapeutic agent in the test individual based on the result of the measurement (hereinafter referred to as the following) , Also referred to as “method for determining the efficacy of the present invention”).
  • test individual showing the pathology of schizophrenia is not particularly limited as long as it is a test individual determined to have a high possibility of schizophrenia.
  • the test individual used may be one that has been determined to have a high possibility of schizophrenia by the test method of the present invention, or one that has been determined to have a high possibility of schizophrenia by a known method. It may be determined that the possibility of schizophrenia is high by a combination thereof.
  • the “test individual showing the pathology of schizophrenia” includes not only those already showing the pathology of schizophrenia but also the pathology of schizophrenia in the future. Those that are highly likely to indicate are also included.
  • test individual used does not show the pathology of schizophrenia before the onset of schizophrenia, but according to the test method of the present invention of the present invention, the possibility of schizophrenia (here, schizophrenia). It may be determined that there is a high possibility of developing symptoms).
  • the test individual may be a human or an animal other than a human, but is preferably a human.
  • the therapeutic agent for schizophrenia may be any therapeutic agent for schizophrenia.
  • “After administration of therapeutic agent” may be appropriately set according to the type of therapeutic agent, the dose of therapeutic agent, the type of subject, and the like. “After administration of a therapeutic agent” can be, for example, any time point from 1 minute to 24 hours after administration of the therapeutic agent, and any time point after 10 minutes to 12 hours. It's okay.
  • Determination of medicinal effect includes determination of the presence or absence of medicinal effect and determination of the degree of medicinal effect.
  • the treatment drug has improved schizophrenia means that the schizophrenia is less likely or less after administration of the treatment compared to before administration of the treatment. It means that the severity of is low. Whether or not schizophrenia has been improved by administration of a therapeutic agent can be determined by comparing the measured values of markers before and after administration of the therapeutic agent.
  • the measured value of the marker approaches the normal value range by administration of the therapeutic agent, it may be determined that schizophrenia has been improved by administration of the therapeutic agent.
  • a marker determined to be positive before administration of a therapeutic agent is determined to be negative after administration, it may be determined that schizophrenia has been improved by administration of the therapeutic agent.
  • the measured value of at least one marker approaches the normal value range by administration of the therapeutic agent, it is determined that schizophrenia has been improved by the administration of the therapeutic agent.
  • the measured values of all the markers approach the normal value range by administration of the therapeutic agent, it may be determined that schizophrenia has been improved by the administration of the therapeutic agent.
  • the number of markers determined to be negative increases due to administration of a therapeutic agent, it may be determined that schizophrenia has been improved by administration of the therapeutic agent.
  • the number of markers determined to be negative by administration of a candidate compound increases, the greater the increase, the greater the degree of improvement of schizophrenia caused by administration of the therapeutic agent Good.
  • the efficacy of a plurality of schizophrenia therapeutic agents is determined and compared in an individual, the most effective schizophrenia therapeutic agent in the individual can be determined.
  • the computer may execute various determination operations in the method as described above using the measurement result of the marker.
  • a medical staff collects blood from a subject, performs pretreatment as necessary, and sets the test sample in the marker measuring device.
  • the computer causes the marker measurement device to measure the marker in the test sample and obtains the measurement result.
  • the computer further determines the possibility of schizophrenia based on the measurement result.
  • the computer can determine the screening result of the model animal, the screening result of the therapeutic drug for schizophrenia, and the efficacy of the therapeutic drug for schizophrenia in the test individual.
  • the computer outputs the determination result thus obtained, and the medical staff can acquire information about the determination result.
  • the program of the present invention is a program for causing a computer to execute various determination operations in the method as described above using the measurement result of the marker.
  • the program of the present invention may further cause the computer to cause the marker measuring device to measure the marker in the test sample.
  • the program of the present invention may be provided by being recorded on a computer-readable recording medium.
  • the computer-readable recording medium is such that information such as data and programs is accumulated by electrical, magnetic, optical, mechanical, chemical action, etc., and the accumulated information is read from the computer.
  • a recording medium for example, floppy (registered trademark) disk, magneto-optical disk, CD-ROM, CD-R / W, DVD-ROM, DVD-R / W, DVD-RAM, DAT, 8 mm tape, memory Examples include a card, a hard disk, a ROM (read only memory), and an SSD.
  • each step executed by the computer may be recorded as a separate program.
  • Example 1 Screening for schizophrenia markers From 18 patients with first-episode psychosis (FEP) and 14 healthy subjects (HC) with controlled age and sex, they were hungry. Sometimes peripheral blood was collected to obtain human plasma. The subject information is shown in Table 1.
  • the analysis was performed in the cation mode and the anion mode, respectively.
  • the analysis conditions are as follows.
  • the sample diluted 2 times was used for the analysis in anion mode.
  • Peaks detected by CE-TOFMS are automatically extracted using the automatic integration software MasterHands ver.2.9.0.9 (developed by Keio University), and peak-to-mass ratio (m / z), migration time) (Migration time; MT) and peak area values were obtained. Each peak was searched for candidate compounds based on the values of m / z and MT, and 175 substances including major metabolites such as amino acids, organic acids, sugar phosphates, and nucleic acids were identified.
  • the obtained peak area value was converted into a relative area value based on the sample amount used and the area value of the internal standard substance, and used for comparison of metabolite concentrations.
  • relative area value obtained peak area value / (area value of internal standard substance ⁇ sample amount).
  • Metabolites that had a significant difference in concentration between the FEP group and the HC group were eight substances, betaine, creatine, glutamic acid, gluconic acid, pelargonic acid, imidazoleacetic acid, perillic acid, and cyclohexylamine.
  • the concentration distributions and P values of these 8 substances in the FEP group and HC group are shown in FIGS.
  • metabolites that had a significant difference in concentration between the 3 cases not taking antipsychotic drugs and the HC group were 3 substances, betaine, pelargonic acid, and cyclohexylamine.
  • the present invention it is possible to accurately and easily predict the onset risk (morbidity risk) of schizophrenia that has been difficult to predict. Further, according to the present invention, it is possible to accurately and easily determine whether or not schizophrenia has been difficult to diagnose. Therefore, the present invention contributes to prevention and early treatment of schizophrenia.

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Abstract

L'invention concerne un procédé de dépistage de la schizophrénie. Un ou plusieurs composés, choisis dans un groupe comprenant la bétaïne, la créatine, l'acide glutamique, l'acide gluconique, l'acide pelargonique, l'acide imidazole acétique, l'acide périllique et la cyclohexylamine, sont mesurés comme marqueurs pour la schizophrénie et un dépistage de la schizophrénie est réalisé sur la base du résultat de la mesure.
PCT/JP2012/080476 2011-11-29 2012-11-26 Procédé d'évaluation objective de la schizophrénie WO2013080917A1 (fr)

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JP2011260626A JP2015034695A (ja) 2011-11-29 2011-11-29 統合失調症の客観的評価法
JP2011-260626 2011-11-29

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WO2013080917A1 true WO2013080917A1 (fr) 2013-06-06

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2015019979A1 (fr) * 2013-08-05 2015-02-12 独立行政法人国立精神・神経医療研究センター Biomarqueur associé à la schizophrénie
WO2021100685A1 (fr) * 2019-11-19 2021-05-27 国立大学法人東京大学 Prévention ou traitement d'une maladie psychiatrique, reposant sur le moteur kif3, et criblage de médicament

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2017119380A1 (fr) * 2016-01-05 2017-07-13 株式会社東京精密 Capteur de déplacement ultrasonore et appareil d'identification de pièce de travail l'utilisant

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JP2009014524A (ja) * 2007-07-05 2009-01-22 Japan Health Science Foundation アレルギー疾患推定マーカー及び治療効果判定マーカー、並びに、それらの利用方法

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JP2009014524A (ja) * 2007-07-05 2009-01-22 Japan Health Science Foundation アレルギー疾患推定マーカー及び治療効果判定マーカー、並びに、それらの利用方法

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Title
DOST ONGUR ET AL: "Creatine abnormalities in shizophrenia and bipolar disorder", PSYCHIATRY RESEARCH: NEUROIMAGING, vol. 172, no. ISS.1, 30 April 2009 (2009-04-30), pages 44 - 48, XP025982024 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2015019979A1 (fr) * 2013-08-05 2015-02-12 独立行政法人国立精神・神経医療研究センター Biomarqueur associé à la schizophrénie
WO2021100685A1 (fr) * 2019-11-19 2021-05-27 国立大学法人東京大学 Prévention ou traitement d'une maladie psychiatrique, reposant sur le moteur kif3, et criblage de médicament

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