[go: up one dir, main page]

WO2011134599A2 - Marqueur quantitatif pour la détermination de l'état mental d'un sujet - Google Patents

Marqueur quantitatif pour la détermination de l'état mental d'un sujet Download PDF

Info

Publication number
WO2011134599A2
WO2011134599A2 PCT/EP2011/001804 EP2011001804W WO2011134599A2 WO 2011134599 A2 WO2011134599 A2 WO 2011134599A2 EP 2011001804 W EP2011001804 W EP 2011001804W WO 2011134599 A2 WO2011134599 A2 WO 2011134599A2
Authority
WO
WIPO (PCT)
Prior art keywords
marker
subjects
mental status
markers
concentration
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/EP2011/001804
Other languages
German (de)
English (en)
Other versions
WO2011134599A3 (fr
Inventor
Carsten Korth
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Individual
Original Assignee
Individual
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Individual filed Critical Individual
Publication of WO2011134599A2 publication Critical patent/WO2011134599A2/fr
Publication of WO2011134599A3 publication Critical patent/WO2011134599A3/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • 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
    • G01N33/6896—Neurological disorders, e.g. Alzheimer's disease
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/30—Psychoses; Psychiatry

Definitions

  • the invention relates to markers that allow a statement about the mental status of a subject.
  • mental status is intended to describe the mental and emotional state of a subject.
  • the possible statement in the context of the invention is a determination as to how far a subject is from mental health.
  • Typical disorders of mental status are caused by brain diseases or chronic mental diseases (CME).
  • CME chronic mental diseases
  • CMEs such as schizophrenia or recurrent affective disorders are among the most common diseases of all.
  • Findings indicating a biological cause e.g. suggestive of schizophrenia are: a strong genetic component, a dopamine metabolism disorder, a subtle disorder of brain development, and bilateral nonspecific, slight enlargement of the ventricles (Chua, 2000, Ross et al., 2006). How these symptoms are related is not yet clear.
  • CME or schizophrenia are diagnosed using operationalized algorithms that retrieve various clinical phenotypes that are requested in a clinical interview;
  • the presence of these phenotypes (usually five - six different according to ICD-10 or DSM-IV) leads to either a positive or a negative diagnosis of a clinically diagnosed CME, which is a serious problem associated with this type of diagnosis.
  • a gradual diagnosis or a course diagnosis that is, the determination of an aggravation or recovery is not possible in this way.
  • scales that try - again by questioning or self-assessment - to establish such gradings in the field of psychological assessment or diagnostics, but these are 1. multidimensional, i. they use perceptions or intellectual achievements of various abilities and 2. they do not include biological variables.
  • Schizophrenia is an example of a disease with complex positives. and negative symptoms. It can not be ruled out that the term schizophrenia covers subtypes of diseases with possibly different biological causes. Furthermore, it is also possible that these subtypes also include overlapping areas with other classically diagnosed mental illnesses such as bipolar disorder, depression, etc. This is supported by examination results, which are discussed below.
  • the DISCl gene is the best characterized gene to date that has been associated with CME.
  • the gene was identified in a Scottish family, in which about 70% of the carriers of a translocation mutation of DISCI also on a CME sufferers (Miliar et al., 2000; St Clair et al., 1990). This mutation could be transgenically expressed in different animal models and also led to behavioral problems, partly in the sense of schizophrenia (pre pulse inhibition) (Clapcote et al., 2007, Hikida et al., 2007, Shen et al., 2008). DISC has been shown to play an important role in the proliferation and migration of neural progenitor cells, thus controlling functions in the proper brain development (Duan et al., 2007, Kamiya et al., 2005).
  • DISC2 is a gene on the genomic antisense sequence of DISC1 (exon 8 and intron 9 of DISC1), which apparently is not translated into a protein; the function of this gene is unknown.
  • WO 2004/071269 e.g. describes genetic markers and compositions for the diagnosis and treatment of neurological disorders.
  • DISCl and FEZ1 Fesciculation and Elongation Protein Zeta 1
  • WO 02/058637 relates to compositions and methods for the diagnosis and treatment of neuropsychiatric disorders. Described are novel polymorphisms of DISC1 nucleic acid sequences and the encoded thereby DISC1 proteins. The sequences or proteins on individual nucleotide variants can be correlated with neuropsychiatric disorders.
  • DE 102008016064 relates to the use of a DISC1 confomer, in particular an aggregated form of DISC1, as a marker for chronic psychiatric disorders.
  • US application US 2005/0255500 relates to methods for the diagnosis of psychiatric disorders in which the molecular diversity or subcellular distribution of DISC1 is examined and correlated with the susceptibility. Based on the observation that DISC1 expression was lower at both mRNA and protein levels in lymphoblasts of especially female patients with bipolar disorders than in healthy subjects, it is postulated that the decrease or loss of DISC1 function or Salary can lead to psychiatric abnormalities. DISC1 -specific antibodies can be used to study expression at the protein level.
  • the susceptibility / predisposition is measured, i. it is a so-called “trait marker” (trait) determined and not a marker that indicates the current, but in principle variable mental status (“state marker”).
  • US 2010/0015130 discloses methods for the treatment of neurological disorders in which, inter alia, DISC1-inducing substances are used which, for example, influence the expression levels of endogenous DISC1 in the sense of an increase in expression. Again, a disease is correlated with a disorder of the DISC1 pathway.
  • classical positive clinical diagnoses of schizophrenia and other clinically diagnosed diseases according to classical criteria are assumed here.
  • Zhang et. al. Neuroscience Letters 438 (2008) investigated the expression of the neuregulin-1 gene in the peripheral blood tissue of schizophrenic subjects. It was found that the expression of the gene can be increased by special antipsychotics. These studies also required a classic positive clinical diagnosis of schizophrenia.
  • the object of the invention to provide markers that allow, in particular in the sense of a state marker, a statement about the mental status of a subject with whom disorders, usually chronic mental illnesses can be defined and differentiated from other diseases and the above In addition, a gradual assessment of the disorders or diseases defined by them can be made possible.
  • markers according to claim 1 comprise proteins which are recognized by an antibody which is generated by the applicant against DISC1 and is designated AK 4DC1.
  • the antibody AK 4DC1 is secreted by the applicant on December 10, 2009 under the number DSM ACC3033 at the DSMZ-German Collection of Microorganisms and Cell Cultures GmbH (Inhoffenstr 7B, D-38124 Braunschweig) Hybrydomazellline with the internal name 4DC1.
  • markers according to the invention allow a quantitative statement, in other words they are gradually detectable in their concentration of proteins whose concentration in tissue samples of a subject a gradual statement about the mental status in the patient allows, the concentration at least one of the marker proteins in tissue samples of healthy subjects is significantly higher than in affected subjects.
  • the present invention in contrast to the aforementioned US 2005/0255500, which relates to methods for measuring the susceptibility / predisposition, in which a so-called “trait marker” (trait) is determined, the present invention thus refers to "state marker", ie markers that indicate the current mental status and in principle is variable intraindividuell.
  • the markers according to the invention are markers which are more pronounced in healthy volunteers than in the case of sick patients and which, in addition, also detect the intermediate area between the two groups.
  • the term healthy should be used to refer to probands in whom the determined marker concentrations indicate no present disturbance of the mental status that can be correlated with these markers, whereas those diagnosed as ill have such a disorder. However, the quantitatively recorded patients are differently ill as recorded by the gradually different marker concentration.
  • the markers according to the invention can detect the degree of the disease.
  • the graduation results from the amount or concentration of the existing markers in the examined tissue; this is in principle variable and dependent on the mental status of the individual.
  • this problem is surprisingly solved, in which quantitatively and quickly measurable, unique markers are described, whose As shown below, increase clearly correlate with the restitution of mental status, the recovery from a chronic mental illness.
  • a gradual biological diagnosis can take place instead of the previously used operationalized either / or (Boolean) diagnosis of chronic mental illness.
  • This has advantages for biological classification, in the delivery of certain therapies or in the follow-up of the disease under a particular therapy.
  • the marker proteins according to the invention consist at least partially of parts of the DISC1 protein.
  • the presence of DISCl, its splice forms, endogenous fusion proteins or degraded fragments is thus measured and thus, in particular, the status of a DISCI-associated brain disease or the status of brain diseases, which ultimately results in a dysfunctional and localized dopamine and / or or cause serotonin and / or acetylcholine and / or glutamate metabolism.
  • the brain disorders they define include at least part of the classically diagnosed clinical pictures of schizophrenia, recurrent monopolar depression, or bipolar disorder, etc.
  • a significant advantage over the prior art in this case is that a variable that is causally linked to the disease mechanism of a brain disease, can be measured and not on phenotypic (raised by clinical interview) indirect features must be used.
  • Another essential further advantage is that the markers according to the invention can be detected in blood without any problems, which enables the conception of a routine test.
  • the subjects tested on the markers according to the invention may also be animals, in particular mammals. Recent studies indicate that disorders in DISC1 metabolism are also associated with e.g. Mice lead to behavioral problems that have some similarities to disorders of mental status in humans. It would be conceivable, for example, that new therapies or medicaments are tested on mice and the success of these measures is checked by means of the markers according to the invention.
  • the markers according to the invention are preferably determined in human subjects.
  • An essential aspect of this is that both healthy and diseased human subjects as target objects in question.
  • the markers according to the invention both the presence of an intact mental status and the opposite can be confirmed.
  • Conceivable is the application in screening tests.
  • the course of all types of therapies, including psychotherapeutic or physical therapies, but especially pharmacotherapies can be controlled.
  • the markers according to the invention are at least two proteins detectable in the Western blot, each having an electrophoretic mobility in the SDS-PAGE gel of about 50 kDa or about 90 kDa. It has long been known that in the group of patients diagnosed clinically as schizophrenia, smoking is excessive compared to the normal population (Leonard and Bertrand, 2001). It is believed that the increased nicotine consumption is a self-medication to compensate for certain cognitive deficits (Adler et al., 1998). It could also be that the large subgroup of smoking schizophrenics is more vulnerable to nicotine addiction, or that the regulatory mechanisms of nicotine addiction and a subset of schizophrenia overlap.
  • the smoking habits of a subject are examined as a further marker.
  • EBPs electrophysiologically measured event-related potentials
  • this inhibition is deficient in 85% of patients clinically diagnosed as schizophrenic (Dawson et al., 2000).
  • this endophenotype could be genetically linked to the acetylcholine receptor subunit (a7AChR) (Freedman et al., 1997) and associated (De Luca et al., 2004).
  • a7AChR acetylcholine receptor subunit
  • This deficit in P50-associated sensory gating can be counterbalanced by nicotine, which may provide an explanation for the excessive nicotine consumption of patients with clinical schizophrenia (Adler et al., 1992).
  • the protein neuregulin which is itself associated with clinically diagnosed schizophrenia, increases a7AChR expression (Liu et al., 2001). It is therefore furthermore preferred that the content of acetylcholine receptors or the protein neuregulin be determined as further markers.
  • the markers according to the invention can be detected in particular in tissues which are suitable for giving indications of the functionality of the central nervous system.
  • tissues, serum, plasma or white blood cells are examined.
  • fabrics are particularly well suited for designing routine processes.
  • the invention not only covers the markers as such, but also methods in which the markers according to the invention are used.
  • the estimation of the subjects may be made by comparing the concentrations measured at the subjects with predetermined concentrations, each for the presence or absence, e.g. a DISC1-correlated chronic mental illness are characteristic.
  • the methods can be used in particular for the diagnosis of chronic mental illnesses, for screening or for controlling the course of a chronic mental illness, monitor the pharmacotherapy of a chronic mental illness whereby the quantitative height of the marker is taken as a statement about the success of (pharmaco) therapy can.
  • the tissue samples taken from the subject e.g. the white blood cells are stimulated with nicotine or other acetylcholine receptor-binding substances to increase the selectivity of said approximately 50 kDa / 90 kDa bands in the context of determining the mental status.
  • a further aspect of the invention relates to the use of the markers according to the invention for the diagnosis of disorders of the mental status, the screening on such disturbances and the course control eg for a pharmacotherapy.
  • FIG. 2 in the form of box plots / bar graphs the results of the quantification of the different immunoreactivity of antibody AK 4DC1 between schizophrenic subjects and controls discussed in Example 2; on the left side are all subjects and controls, on the right side only the smoking ones, i. Nicotine-stimulated schizophrenic subjects and non-nauseated smokers. The differences are highly significant and become more pronounced when compared specifically to smokers.
  • the positive clone AK 4DC1 recognized DISC1 immunoreactivity in human white blood cells purified by standard methods while other described antibodies did not show the same immunoreactivity ( Figure 1). Thus, the AK 4DC1 has new features that have not yet been described.
  • Example 2 The positive clone AK 4DC1 recognized DISC1 immunoreactivity in human white blood cells purified by standard methods while other described antibodies did not show the same immunoreactivity ( Figure 1). Thus, the AK 4DC1 has new features that have not yet been described.
  • white blood cells were purified by standard methods. The white blood cells were lysed and equal amounts of protein were separated by SDS-PAGE (sodium dodecyl sulfate polyacrylamide gel electrophoresis). After transfer of the proteins to a nitrocellulose membrane, Western blotting was performed with AK 4DC1. The immunoreactivity for the approximately 90 kDa and the approximately 50 kDa bands was blindly quantified and evaluated in relation to the diagnosis of the samples.
  • SDS-PAGE sodium dodecyl sulfate polyacrylamide gel electrophoresis
  • the densitometric evaluation was carried out with the freeware NIH Image.
  • the film on which the Western blot was exposed is scanned in and the number of pixels in the material defined by the immunoreactivity is counted. Normalizations with reference values were made to compare different blots. Since the white pixels were counted, those values are higher which have a lower immunoreactivity with AK 4DC1.
  • FIG. 2 shows so-called box plots / bar graphs of 4 different group comparisons of immunoreactivity with AK 4DC1 in Western blot of lysed white blood cells (from left to right): 1. all normal controls (N) vs. all schizophrenics (S) densitometric comparison of the ca. 90 kDa band, 2. idem, but densitometric comparison of the ca. 50 kDa band; 3. as a subgroup, 8 schizophrenics / nicotine addicts / smokers vs. 8 healthy nicotine addicts / smokers compared in terms of immunoreactivity of the approximately 90 kDa band and 4th (far right) of the approximately 50 kDa band. It was from the number of Pixel averages (number in box) are made and the bars indicate the standard deviation. Statistical significance was determined by Student's t-test and is given below.
  • a hybridoma cell line secreting the antibody AK 4DC1 was deposited on December 10, 2009 under the number DSM ACC3033 and the internal name 4DC1 in the DSMZ-German Collection of Microorganisms and Cell Cultures GmbH (Inhoffenstr 7B, D-38124 Braunschweig). References:
  • Schizophrenia sensory gating, and nicotinic receptors. Schizophrenia Bull 24, 189-202.
  • Oligomer assembly of the C-terminal DISC1 domain (640-854) is controlled by self-association motifs and disease-associated polymorphism S704C. Biochemistry 48, 7746-7755.

Landscapes

  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Hematology (AREA)
  • Chemical & Material Sciences (AREA)
  • Urology & Nephrology (AREA)
  • Molecular Biology (AREA)
  • Immunology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Medicinal Chemistry (AREA)
  • Microbiology (AREA)
  • Biotechnology (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Food Science & Technology (AREA)
  • Cell Biology (AREA)
  • Physics & Mathematics (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Pathology (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)

Abstract

L'invention concerne des marqueurs quantitatifs pour la détermination de l'état mental d'un sujet, comprenant des protéines dont la concentration peut être déterminée graduellement et détectées par un anticorps désigné par AK 4DC1. Leur concentration dans des échantillons de tissu d'un sujet permet de donner une indication graduelle de l'état mental du sujet, la concentration en au moins une des protéines de marqueur dans les échantillons de tissu de sujets sains étant considérablement plus élevée que chez les sujets malades.
PCT/EP2011/001804 2010-04-28 2011-04-12 Marqueur quantitatif pour la détermination de l'état mental d'un sujet Ceased WO2011134599A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE102010018561.2 2010-04-28
DE201010018561 DE102010018561B4 (de) 2010-04-28 2010-04-28 Quantitative Marker zur Bestimmung des mentalen Status eines Probanden

Publications (2)

Publication Number Publication Date
WO2011134599A2 true WO2011134599A2 (fr) 2011-11-03
WO2011134599A3 WO2011134599A3 (fr) 2012-01-19

Family

ID=44118711

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2011/001804 Ceased WO2011134599A2 (fr) 2010-04-28 2011-04-12 Marqueur quantitatif pour la détermination de l'état mental d'un sujet

Country Status (2)

Country Link
DE (1) DE102010018561B4 (fr)
WO (1) WO2011134599A2 (fr)

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002058637A2 (fr) 2001-01-24 2002-08-01 Millenium Pharmaceuticals, Inc. Compositions et methodes servant au diagnostic et au traitement de troubles neuropsychiatriques, tels que la schizophrenie
WO2004071269A2 (fr) 2003-02-13 2004-08-26 Intellectual Property Consulting Inc. Marqueur de gene et composition de diagnostic et de traitement de troubles et de maladies neurologiques et utilisation de ceux-ci
US20050255500A1 (en) 2004-01-28 2005-11-17 Johns Hopkins University Method for diagnosing or predicting susceptibility to psychiatric disorders
DE102008016064A1 (de) 2008-03-26 2009-10-01 Carsten Dr. Korth Verfahren zur Diagnose und Behandlung von chronisch psychiatrischen Erkrankungen sowie Marker und Targets für solche Verfahren
US20100015130A1 (en) 2008-05-28 2010-01-21 Massachusetts Institute Of Technology Disc-1 pathway activators in the control of neurogenesis

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003099995A2 (fr) * 2002-05-24 2003-12-04 Merck & Co., Inc. Orthologue murin du gene humain de la proteine disc-1 (disrupted in schizophrenia 1 gene)
DE102004007462A1 (de) * 2004-02-13 2005-09-15 Heinrich-Heine-Universität Düsseldorf Antikörper sowie Verfahren zur Diagnose und Behandlung von Schizophrenie
GB0724735D0 (en) 2007-12-19 2008-01-30 Psynova Neurotech Ltd Methods and biomarkers for diagnosing and monitoring psychotic disorders

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002058637A2 (fr) 2001-01-24 2002-08-01 Millenium Pharmaceuticals, Inc. Compositions et methodes servant au diagnostic et au traitement de troubles neuropsychiatriques, tels que la schizophrenie
WO2004071269A2 (fr) 2003-02-13 2004-08-26 Intellectual Property Consulting Inc. Marqueur de gene et composition de diagnostic et de traitement de troubles et de maladies neurologiques et utilisation de ceux-ci
US20050255500A1 (en) 2004-01-28 2005-11-17 Johns Hopkins University Method for diagnosing or predicting susceptibility to psychiatric disorders
DE102008016064A1 (de) 2008-03-26 2009-10-01 Carsten Dr. Korth Verfahren zur Diagnose und Behandlung von chronisch psychiatrischen Erkrankungen sowie Marker und Targets für solche Verfahren
US20100015130A1 (en) 2008-05-28 2010-01-21 Massachusetts Institute Of Technology Disc-1 pathway activators in the control of neurogenesis

Non-Patent Citations (20)

* Cited by examiner, † Cited by third party
Title
ADLER, L.E., HOFFER, L.J., GRIFFITH, J., WALDO, M.C., FREEDMAN, R.: "Normalization by nicotine ofdeficient auditory sensory gating in the relatives of schizophrenics", BIOL PSYCHIATRY, vol. 32, 1992, pages 607 - 616, XP024249556, DOI: doi:10.1016/0006-3223(92)90073-9
ADLER, L.E., OLINCY, A., WALDO, M., HARRIS, J.G., GRIFFITH, J., STEVENS, K., FLACH, K., NAGAMOTO, H., BICKFORD, P., LEONARD, S. ET: "Schizophrenia, sensory gating, and nicotinic receptors", SCHIZOPHR BULL, vol. 24, 1998, pages 189 - 202
CHUA, S.E., MCKENNA, P.J.: "The Neuropathology of Schizophrenia", 2000, OXFORD UNIVERSITY PRESS, article "A Sceptical View of the Neuropathology of Schizophrenia", pages: 291 - 337
CLAPCOTE, S.J., LIPINA, T.V., MILLAR, J.K., MACKIE, S., CHRISTIE, S., OGAWA, F., LERCH, J.P., TRIMBLE, K., UCHIYAMA, M., SAKURABA,: "Behavioral phenotypes ofDiscl missense mutations in mice", NEURON, vol. 54, 2007, pages 387 - 402
DAWSON, M.E., SCHELL, A.M., HAZLETT, E.A., NUECHTERLEIN, K.H., FILION, D.L.: "On the clinical and cognitive meaning of impaired sensorimotor gating in schizophrenia", PSYCHIATRY RES, vol. 96, 2000, pages 187 - 197
DE LUCA, V., WONG, A.H., MULLER, D.J., WONG, G.W., TYNDALE, R.F., KENNEDY, J.L.: "Evidence of association between smoking and alpha7 nicotinic receptor subunit gene in schizophrenia patients", NEUROPSYCHOPHARMACOLOGY, vol. 29, 2004, pages 1522 - 1526
DUAN, X., CHANG, J.H., GE, S., FAULKNER, R.L., KIM, J.Y., KITABATAKE, Y., LIU, X.B., YANG, C.H., JORDAN, J.D., MA, D.K. ET AL.: "Disrupted-In-Schizophrenia 1 regulates integration of newly generated neurons in the adult brain", CELL, vol. 130, 2007, pages 1146 - 1158
FREEDMAN, R., COON, H., MYLES-WORSLEY, M., ORR-URTREGER, A., OLINCY, A., DAVIS, A., POLYMEROPOULOS, M., HOLIK, J., HOPKINS, J., HO: "Linkage of a neurophysiological deficit in schizophrenia to a chromosome 15 locus", PROC NATL ACAD SEI U S A, vol. 94, 1997, pages 587 - 592
HARRISON, P.J., WEINBERGER, D.R.: "Schizophrenia genes, gene expression, and neuropathology: on the matter of their convergence", MOL PSYCHIATRY, vol. 10, 2005, pages 40 - 68, XP009061024, DOI: doi:10.1038/sj.mp.4001558
HIKIDA, T., JAARO-PELED, H., SESHADRI, S., OISHI, K., HOOKWAY, C., KONG, S., WU, D., XUE, R., ANDRADE, M., TANKOU, S. ET AL.: "Dominant-negative DISC 1 transgenic mice display schizophrenia-associated phenotypes detected by measures translatable to humans", PROC NATL ACAD SEI U S A, vol. 104, 2007, pages 14501 - 14506, XP002523122, DOI: doi:10.1073/pnas.0704774104
KAMIYA, A., KUBO, K., TOMODA, T., TAKAKI, M., YOUN, R., OZEKI, Y., SAWAMURA, N., PARK, U., KUDO, C., OKAWA, M. ET AL.: "A schizophrenia-associated mutation of DISC perturbs cerebral cortex development", NAT CELL BIOL, vol. 7, 2005, pages 1167 - 1178
LELIVELD, S.R., BADER, V., HENDRIKS, P., PRIKULIS, I., SAJNANI, G., REQUENA, J.R., KORTH, C.: "Insolubility of disrupted-in-schizophrenia 1 disrupts oligomer-dependent interactions with nuclear distribution element 1 and is associated with sporadic mental disease", J NEUROSCI, vol. 28, 2008, pages 3839 - 3845, XP009103840, DOI: doi:10.1523/JNEUROSCI.5389-07.2008
LELIVELD, S.R., HENDRIKS, P., MICHEL, M., SAJNANI, G., BADER, V., TROSSBACH, S., PRIKULIS, I., HARTMANN, R., JONAS, E., WILLBOLD,: "Oligomer assembly of the C-terminal DISC domain (640-854) is controlled by selfassociation motifs and disease-associated polymorphism S704C", BIOCHEMISTRY, vol. 48, 2009, pages 7746 - 7755
LEONARD, S., BERTRAND, D.: "Neuronal nicotinic receptors: from structure to function", NICOTINE TOB RES, vol. 3, 2001, pages 203 - 223
LIU, Y., FORD, B., MANN, M.A., FISCHBACH, G.D.: "Neuregulins increase alpha7 nicotinic acetylcholine receptors and enhance excitatory synaptic transmission in GABAergic interneurons of the hippocampus", J NEUROSCI, vol. 21, 2001, pages 5660 - 5669
MILLAR, J.K., WILSON-ANNAN, J.C., ANDERSON, S., CHRISTIE, S., TAYLOR, M.S., SEMPLE, C.A., DEVON, R.S., CLAIR, D.M., MUIR, W.J., BL: "Disruption of two novel genes by a translocation co-segregating with schizophrenia", HUM MOL GENET, vol. 9, 2000, pages 1415 - 1423, XP002952129, DOI: doi:10.1093/hmg/9.9.1415
ROSS, C.A., MARGOLIS, R.L., READING, S.A., PLETNIKOV, M., COYLE, J.T.: "Neurobiology of schizophrenia", NEURON, vol. 52, 2006, pages 139 - 153
SHEN, S., LANG, B., NAKAMOTO, C., ZHANG, F., PU, J., KUAN, S.L., CHATZI, C., HE, S., MACKIE, I., BRANDON, N.J. ET AL.: "Schizophrenia-related neural and behavioral phenotypes in transgenic mice expressing truncated Disc 1.", J NEUROSCI, vol. 28, 2008, pages 10893 - 10904, XP002550146, DOI: doi:10.1523/JNEUROSCI.3299-08.2008
ST CLAIR, D., BLACKWOOD, D., MUIR, W., CAROTHERS, A., WALKER, M., SPOWART, G., GOSDEN, C., EVANS, H.J.: "Association within a family of a balanced autosomal translocation with major mental illness", LANCET, vol. 336, 1990, pages 13 - 16
ZHANG, NEUROSCIENCE LETTERS, 2008, pages 438

Also Published As

Publication number Publication date
DE102010018561B4 (de) 2012-04-12
DE102010018561A1 (de) 2011-11-03
WO2011134599A3 (fr) 2012-01-19

Similar Documents

Publication Publication Date Title
EP2030023B1 (fr) Procédé multiparamètre de détermination in vitro pour le diagnostic et le diagnostic précoce de maladies dementielles
Santos et al. Change in retinal structural anatomy during the preclinical stage of Alzheimer's disease
Piguet et al. Eating and hypothalamus changes in behavioral‐variant frontotemporal dementia
Mu et al. Alpha-synuclein pathology and axonal degeneration of the peripheral motor nerves innervating pharyngeal muscles in Parkinson disease
Waldo et al. Auditory sensory gating, hippocampal volume, and catecholamine metabolism in schizophrenics and their siblings
DE69632734T2 (de) QUANTIFIZIERUNG VON p97 ZUR DIAGNOSE UND ÜBERWACHUNG DER ALZHEIMHER-KRANKHEIT
Beitchman et al. Experimental traumatic brain injury induces chronic glutamatergic dysfunction in amygdala circuitry known to regulate anxiety-like behavior
Quintá et al. Glycan-dependent binding of galectin-1 to neuropilin-1 promotes axonal regeneration after spinal cord injury
Goetz et al. Computerized axial tomography scans and subtypes of schizophrenia: A review of the literature
Jönsson et al. Hippocampal pyramidal cell disarray correlates negatively to cell number: implications for the pathogenesis of schizophrenia
Jurick et al. Faulty adaptation to repeated face-name associative pairs in mild cognitive impairment is predictive of cognitive decline
Förster et al. Reduced GABAergic neuropil and interneuron profiles in schizophrenia: Complementary analysis of disease course-related differences
Arendt et al. Clinicopathologic correlations and the brain—behaviour relationship in Alzheimer's disease
EP2016418B1 (fr) Procede in vitro pour le diagnostic et le diagnostic precoce de maladies neurodegeneratives
Yao et al. Abnormal resting-state functional connectivity of hippocampal subregions in type 2 diabetes mellitus-associated cognitive decline
EP1904855B1 (fr) Procede de diagnostic du liquide cerebro-spinal in vitro destine au diagnostic de demence et de maladies neuro-inflammatoires
Ioakeimidis et al. Functional neurodevelopment of working memory in early-onset schizophrenia: a longitudinal FMRI study
Sasaki et al. Immunocytochemical and ultrastructural study of the motor cortex in patients with lower motor neuron disease
DE102010018561B4 (de) Quantitative Marker zur Bestimmung des mentalen Status eines Probanden
DE60126991T2 (de) Verfahren ZUR DIAGNOSE VON SCHIZOPHRENIE
Damadzic et al. Neuritic pathology is lacking in the entorhinal cortex, subiculum and hippocampus in middle-aged adults with schizophrenia, bipolar disorder or unipolar depression
Mayer et al. An examination of behavioral and neuronal effects of comorbid traumatic brain injury and alcohol use
DE60033646T2 (de) Methoden zur diagnostizierung oder zur behandlung der alzheimer krankheit
WO2009118151A1 (fr) Procédés de diagnostic et de traitement de maladies psychiatriques chroniques et marqueurs et cibles pour ces procédés
WO2008138475A1 (fr) Utilisation de crmp1 en tant que marqueurs pour des maladies ppsychiatriques chroniques et anticoprs monoclonaux contre crmp1

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 11721227

Country of ref document: EP

Kind code of ref document: A2

122 Ep: pct application non-entry in european phase

Ref document number: 11721227

Country of ref document: EP

Kind code of ref document: A2