Expression analysis in a rat psychosis model identifies novel candidate genes validated in a large case-control sample of schizophrenia

A. Ingason, I. Giegling, A. M. Hartmann, J. Genius, B. Konte, M. Friedl, S. Ripke, P. F. Sullivan, D. St Clair, D. A. Collier, M. C. O'Donovan, K. Mirnics, D. Rujescu (Corresponding Author)

Research output: Contribution to journalArticle

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Abstract

Antagonists of the N-methyl-D-aspartate (NMDA)-type glutamate receptor induce psychosis in healthy individuals and exacerbate schizophrenia symptoms in patients. In this study we have produced an animal model of NMDA receptor hypofunction by chronically treating rats with low doses of the NMDA receptor antagonist MK-801. Subsequently, we performed an expression study and identified 20 genes showing altered expression in the brain of these rats compared with untreated animals. We then explored whether the human orthologs of these genes are associated with schizophrenia in the largest schizophrenia genome-wide association study published to date, and found evidence for association for 4 out of the 20 genes: SF3B1, FOXP1, DLG2 and VGLL4. Interestingly, three of these genes, FOXP1, SF3B1 and DLG2, have previously been implicated in neurodevelopmental disorders.

Original languageEnglish
Article numbere656
Number of pages6
JournalTranslational Psychiatry
Volume5
DOIs
Publication statusPublished - 13 Oct 2015

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Psychotic Disorders
Schizophrenia
N-Methyl-D-Aspartate Receptors
Genes
Dizocilpine Maleate
Genome-Wide Association Study
Glutamate Receptors
Animal Models
Brain

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Biological Psychiatry

Cite this

Expression analysis in a rat psychosis model identifies novel candidate genes validated in a large case-control sample of schizophrenia. / Ingason, A.; Giegling, I.; Hartmann, A. M.; Genius, J.; Konte, B.; Friedl, M.; Ripke, S.; Sullivan, P. F.; St Clair, D.; Collier, D. A.; O'Donovan, M. C.; Mirnics, K.; Rujescu, D. (Corresponding Author).

In: Translational Psychiatry, Vol. 5, e656, 13.10.2015.

Research output: Contribution to journalArticle

Ingason, A, Giegling, I, Hartmann, AM, Genius, J, Konte, B, Friedl, M, Ripke, S, Sullivan, PF, St Clair, D, Collier, DA, O'Donovan, MC, Mirnics, K & Rujescu, D 2015, 'Expression analysis in a rat psychosis model identifies novel candidate genes validated in a large case-control sample of schizophrenia' Translational Psychiatry, vol. 5, e656. https://doi.org/10.1038/tp.2015.151
Ingason, A. ; Giegling, I. ; Hartmann, A. M. ; Genius, J. ; Konte, B. ; Friedl, M. ; Ripke, S. ; Sullivan, P. F. ; St Clair, D. ; Collier, D. A. ; O'Donovan, M. C. ; Mirnics, K. ; Rujescu, D. / Expression analysis in a rat psychosis model identifies novel candidate genes validated in a large case-control sample of schizophrenia. In: Translational Psychiatry. 2015 ; Vol. 5.
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abstract = "Antagonists of the N-methyl-D-aspartate (NMDA)-type glutamate receptor induce psychosis in healthy individuals and exacerbate schizophrenia symptoms in patients. In this study we have produced an animal model of NMDA receptor hypofunction by chronically treating rats with low doses of the NMDA receptor antagonist MK-801. Subsequently, we performed an expression study and identified 20 genes showing altered expression in the brain of these rats compared with untreated animals. We then explored whether the human orthologs of these genes are associated with schizophrenia in the largest schizophrenia genome-wide association study published to date, and found evidence for association for 4 out of the 20 genes: SF3B1, FOXP1, DLG2 and VGLL4. Interestingly, three of these genes, FOXP1, SF3B1 and DLG2, have previously been implicated in neurodevelopmental disorders.",
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