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Detection and Treatment of Schizophrenia

a treatment method and schizophrenia technology, applied in the field of diagnosis of schizophrenia, can solve the problems of inability to determine the decisive treatment method, inability to analyze the candidate gene of various researchers, and inability to explain the pathological condition in terms of biochemistry, so as to achieve the effect of reducing the stress of carbonyl compounds, facilitating and objectively making, and improving the condition

Active Publication Date: 2012-03-15
TOKYO METROPOLITAN INST OF MEDICAL SCI +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0119] According to the diagnostic method of the present invention, at least one parameter selected from the group consisting of: (1) a genetic abnormality of glyoxalase I gene; (2) the expression level or activity of glyoxalase I in a biological sample; (3) the amount of a carbonyl compound or a carbonyl-modified protein that is a protein modified with the carbonyl compound; and (4) the amount of pyridoxal in a biological sample is measured in a subject, and the obtained value is used as an indicator, whereby the diagnosis of schizophrenia, which conventionally depended on a doctor's subjective judgment based on inquiries to the patient, can be easily and objectively made. Further, according to the present invention, a compound having an effect of carbonyl removal (a carbonyl scavenger effect) or an inhibitory effect on AGE formation is used to inhibit carbonyl stress in patients, whereby schizophrenia can be treated or the condition can be ameliorated. The therapeutic or ameliorating agent for schizophrenia according to the present invention is particularly effective for schizophrenia caused by carbonyl stress resulting from glyoxalase I gene abnormality.
[0120] According to the screening method of the present invention, a substance effective for treating or ameliorating schizophrenia, i.e., a therapeutic or ameliorating agent for schizophrenia can be easily selected from test substances and obtained by using carbonyl-removing effects or AGE formation inhibitory effects as an indicator. The screening method of the present invention is effective as a method for searching for a substance effective for treating and ameliorating schizophrenia caused by carbonyl stress resulting from glyoxalase I gene abnormality.DESCRIPTION

Problems solved by technology

As described later herein, only symptomatic medication is used for the main treatment, and no decisive therapeutic method has yet to be established.
Although several candidate genes have been identified by positional approaches, the pathological conditions are still inexplicable in terms of biochemistry etc.
Moreover, the results of the candidate gene analyses of various researchers are inconsistent.
Thus, diagnoses are not always sufficiently accurate.
However, no decisive method has yet to be established.
However, since the inhibition of dopamine neurons causes Parkinsonian symptoms as side effects, an anti-Parkinson's agent is generally used with the antipsychotic.
However, these methods are all symptomatic treatments.

Method used

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  • Detection and Treatment of Schizophrenia
  • Detection and Treatment of Schizophrenia
  • Detection and Treatment of Schizophrenia

Examples

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example 1

Genetic and Biochemical Analyses on Patient with Severe Schizophrenia

[0519] A schizophrenic patient (male, 60 years, weight 75.5 kg) hospitalized in a psychiatric hospital (hereinafter “Patient A”) underwent analysis of the glyoxalase I gene, as well as measurement of the erythrocyte glyoxalase activity, the serum AGE level, and the quantity of serum vitamin B6. Patient A is one of four siblings, two of whom committed suicide; he and the other remaining sibling are currently hospitalized in a psychiatric hospital. Patient A has been diagnosed with severe familial schizophrenia.

[0520] Measurement Methods

[0521] (1) Measurement of Erythrocyte Glyoxalase Activity

[0522] The erythrocyte glyoxalase activity was measured according to the method of McLellan et al. (McLellan A C, Thornalley P J: Glyoxalase activity in human red blood cells fractioned by age. Mech Ageing Dev 48: 63-71, 1989). Specifically, disrupted erythrocytes were added to a hemithioacetal solution produced from methylg...

example 2

Measurement of the AGE Content in the Skin

[0538] AGE contents in the skin were measured in healthy subjects (12 females and 12 males, a total of 24 subjects; average age: 48.88+3.17 years) and schizophrenic patients (12 females and 12 males, a total of 24 subjects; average age: 48.38+2.23 years), using an AGE Reader (manufactured by DiagnOptics, the Netherlands).

[0539]FIG. 7 shows a comparison of the AGE contents in the skin between the healthy subjects and schizophrenic patients. The results show that the AGE contents in the skin of the schizophrenic patients are significantly increased as compared to those of the healthy subjects. FIG. 8A and FIG. 8B show comparison of the AGE contents in the skin between the healthy subjects and schizophrenic patients according to age. The results revealed a strong positive correlation between the AGE content and age for the healthy subjects, but no such correlation was observed for the schizophrenic patients (FIG. 8A). However, as shown in FIG...

example 3

Analysis of Glyoxalase I Gene of Schizophrenic Patients

[0541] (1) Analysis of the glyoxalase I (GLO-I) gene was conducted on schizophrenic patients (n=700) and healthy subjects (n=600).

[0542] A frameshift mutation in the GLO-I gene (an insertion of a single base between positions 79 and 80 of the base sequence (SEQ ID NO: 1) of the coding region of the GLO-I gene) was identified by PCR-direct sequencing using Blend Taq (TOYOBO Cat#BTQ-101S), in which PCR was performed using PCR primers, F: 5′-GAGTTTGCCTCCTTTATGCG-3′ (SEQ ID NO: 8) and R: 5′-AACAGATCCCCTCCACACTT-3′ (SEQ ID NO: 9), under the conditions of (i) 1 cycle of 94° C. for 2 minutes; (ii) 40 cycles of 94° C. for 30 seconds, 62.5° C. for 20 seconds, 72° C. for 30 seconds; and (iii) 1 cycle of 72° C. for 2 minutes. A base substitution mutation (the mutation of alanine to cytosine at position 332 of the base sequence (SEQ ID NO: 1) of the coding region of the GLO-I gene), inducing the mutation of the amino acid (Glu→Ala) at pos...

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Abstract

The present invention provides a method for diagnosing schizophrenia, and a schizophrenia diagnostic reagent or device for use in the method. The present invention further provides a therapeutic or ameliorating agent for schizophrenia, which is effective for the treatment or amelioration of schizophrenia. The therapeutic or ameliorating agent for schizophrenia contains a carbonyl scavenger or a carbonyl-modified protein formation inhibitor as an active ingredient. The method for diagnosing schizophrenia according to the present invention includes measuring at least one parameter in a subject, the parameter being selected from the group consisting of: (1) a genetic abnormality of glyoxalase I gene; (2) the expression level or activity of glyoxalase I in a biological sample; (3) the amount of a carbonyl compound or a carbonyl-modified protein that is a protein modified with the carbonyl compound; and (4) the amount of pyridoxal in a biological sample.

Description

TECHNICAL FIELD [0001] The present invention provides a method for diagnosing schizophrenia, and a schizophrenia diagnostic reagent or device for use in the method. The present invention further provides a therapeutic or ameliorating agent for schizophrenia, which is effective for the treatment or amelioration of schizophrenia. BACKGROUND ART [0002]“Integration dysfunction syndrome” (schizophrenia), formerly called “mind-split-disease”, is a typical psychiatric disorder characterized by hallucinations and delusions. Schizophrenia affects about 1% of the population, and 700,000 people are currently under treatment for schizophrenia in Japan. Late adolescence and early adulthood from the ages of 17 to 27 are the peak years for the onset of schizophrenia, and the disorder becomes chronic after those ages. Therefore, in 1996, patients with schizophrenia occupied 22% of all hospital beds. The peak years for males for the onset of this disorder are the ages of from 15 to 24, whereas the p...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K31/5355A61P25/18A61K31/4152A61K31/4355A61K31/4155A61K31/416A61K31/4709A61K31/44A61K31/427
CPCA61K31/415C12Q2600/112A61K31/437A61K31/4415A61K31/4439C12Q1/6883C12Q2600/158G01N33/6893G01N2333/988C12Q2600/106C12Q2600/136C12Q2600/156C12Q1/527C12Q1/686A61K31/4152A61P25/00A61P25/18A61P43/00
Inventor ITOKAWA, MASANARIMIYATAARAI, MAKOTO
Owner TOKYO METROPOLITAN INST OF MEDICAL SCI