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

doi:10.1038/tp.2015.151

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)

^*Corresponding author for this work

Applied Medicine

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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 language	English
Article number	e656
Number of pages	6
Journal	Translational Psychiatry
Volume	5
DOIs	https://doi.org/10.1038/tp.2015.151
Publication status	Published - 13 Oct 2015

Bibliographical note

ACKNOWLEDGMENTS
We thank the participating subjects for making this study possible. Parts of this study were supported by the German Federal Ministry of Education and Research (BMBF) through the Integrated Network IntegraMent (Integrated Understanding of Causes and Mechanisms in Mental Disorders), under the auspices of the e:Med Programme (grant 01ZX1314).

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Expression analysis in a rat psychosis model identifies novel candidate genes validated in a large case–control sample of schizophrenia
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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. (2015). Expression analysis in a rat psychosis model identifies novel candidate genes validated in a large case-control sample of schizophrenia. Translational Psychiatry, 5, Article e656. https://doi.org/10.1038/tp.2015.151

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

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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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note = "ACKNOWLEDGMENTS We thank the participating subjects for making this study possible. Parts of this study were supported by the German Federal Ministry of Education and Research (BMBF) through the Integrated Network IntegraMent (Integrated Understanding of Causes and Mechanisms in Mental Disorders), under the auspices of the e:Med Programme (grant 01ZX1314).",

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AU - Rujescu, D.

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

Abstract

Bibliographical note

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