title: Expression analysis in a rat psychosis model identifies novel candidate genes validated in a large case-control sample of schizophrenia.
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.
authors.affiliation: Department of Psychiatry, University of Halle-Wittenberg, Halle, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Ingason
authors.affiliation: Department of Psychiatry, University of Halle-Wittenberg, Halle, Germany.
authors.forename: I
authors.initials: I
authors.lastname: Giegling
authors.affiliation: Department of Psychiatry, University of Halle-Wittenberg, Halle, Germany.
authors.forename: A M
authors.initials: AM
authors.lastname: Hartmann
authors.affiliation: Department of Psychiatry, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Genius
authors.affiliation: Department of Psychiatry, University of Halle-Wittenberg, Halle, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Konte
authors.affiliation: Department of Psychiatry, University of Halle-Wittenberg, Halle, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Friedl
authors.affiliation: Analytical and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Ripke
authors.affiliation: Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: P F
authors.initials: PF
authors.lastname: Sullivan
authors.affiliation: Department of Mental Health, University of Aberdeen, Aberdeen, UK.
authors.forename: D
authors.initials: D
authors.lastname: St Clair
authors.affiliation: King's College London, Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, London, UK.
authors.forename: D A
authors.initials: DA
authors.lastname: Collier
authors.affiliation: Institute of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK.
authors.forename: M C
authors.initials: MC
authors.lastname: O'Donovan
authors.affiliation: Department of Psychiatry, Kennedy Center for Research on Human Development, Vanderbilt University, Nashville, TN, USA.
authors.forename: K
authors.initials: K
authors.lastname: Mirnics
authors.affiliation: Department of Psychiatry, University of Halle-Wittenberg, Halle, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Rujescu
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D016022:Case-Control Studies; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics*; D055106:Genome-Wide Association Study; D051528:Guanylate Kinases / Q000235:genetics*; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010750:Phosphoproteins / Q000235:genetics*; D011619:Psychotropic Drugs / Q000494:pharmacology; D000072260:RNA Splicing Factors; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D012097:Repressor Proteins / Q000235:genetics*; D017413:Ribonucleoprotein, U2 Small Nuclear / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: C486626:FOXP1 protein, human; D051858:Forkhead Transcription Factors; D010750:Phosphoproteins; D011619:Psychotropic Drugs; D000072260:RNA Splicing Factors; D016194:Receptors, N-Methyl-D-Aspartate; D012097:Repressor Proteins; D017413:Ribonucleoprotein, U2 Small Nuclear; C112491:SF3B1 protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C488533:VGLL4 protein, human; D016291:Dizocilpine Maleate; C496468:DLG2 protein, human; D051528:Guanylate Kinases