title: Expression of DISC1-interactome members correlates with cognitive phenotypes related to schizophrenia.
abstract: Cognitive dysfunction is central to the schizophrenia phenotype. Genetic and functional studies have implicated Disrupted-in-Schizophrenia 1 (DISC1), a leading candidate gene for schizophrenia and related psychiatric conditions, in cognitive function. Altered expression of DISC1 and DISC1-interactors has been identified in schizophrenia. Dysregulated expression of DISC1-interactome genes might, therefore, contribute to schizophrenia susceptibility via disruption of molecular systems required for normal cognitive function. Here, the blood RNA expression levels of DISC1 and DISC1-interacting proteins were measured in 63 control subjects. Cognitive function was assessed using neuropsychiatric tests and functional magnetic resonance imaging was used to assess the activity of prefrontal cortical regions during the N-back working memory task, which is abnormal in schizophrenia. Pairwise correlations between gene expression levels and the relationship between gene expression levels and cognitive function and N-back-elicited brain activity were assessed. Finally, the expression levels of DISC1, AKAP9, FEZ1, NDEL1 and PCM1 were compared between 63 controls and 69 schizophrenic subjects. We found that DISC1-interactome genes showed correlated expression in the blood of healthy individuals. The expression levels of several interactome members were correlated with cognitive performance and N-back-elicited activity in the prefrontal cortex. In addition, DISC1 and NDEL1 showed decreased expression in schizophrenic subjects compared to healthy controls. Our findings highlight the importance of the coordinated expression of DISC1-interactome genes for normal cognitive function and suggest that dysregulated DISC1 and NDEL1 expression might, in part, contribute to susceptibility for schizophrenia via disruption of prefrontal cortex-dependent cognitive functions.
authors.affiliation: Medical Genetics Section, Centre for Genomic and Experimental Medicine, Medical Research Council Institute of Genetics and Molecular Medicine, The University of Edinburgh, Edinburgh, United Kingdom; Department of Neuroscience and Sense Organs, University of Bari, Bari, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Rampino
authors.affiliation: Medical Genetics Section, Centre for Genomic and Experimental Medicine, Medical Research Council Institute of Genetics and Molecular Medicine, The University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Rosie May
authors.initials: RM
authors.lastname: Walker
authors.affiliation: Medical Genetics Section, Centre for Genomic and Experimental Medicine, Medical Research Council Institute of Genetics and Molecular Medicine, The University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Helen Scott
authors.initials: HS
authors.lastname: Torrance
authors.affiliation: Medical Genetics Section, Centre for Genomic and Experimental Medicine, Medical Research Council Institute of Genetics and Molecular Medicine, The University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Susan Maguire
authors.initials: SM
authors.lastname: Anderson
authors.affiliation: Department of Neuroscience and Sense Organs, University of Bari, Bari, Italy.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Fazio
authors.affiliation: Department of Neuroscience and Sense Organs, University of Bari, Bari, Italy; Istituti di Ricovero e Cura a Carattere Scientifico Casa Sollievo della Sofferenza, Section of Liaison Psychiatry, San Giovanni Rotondo (FG), Italy.
authors.forename: Annabella
authors.initials: A
authors.lastname: Di Giorgio
authors.affiliation: Department of Neuroscience and Sense Organs, University of Bari, Bari, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Taurisano
authors.affiliation: Department of Neuroscience and Sense Organs, University of Bari, Bari, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Gelao
authors.affiliation: Department of Neuroscience and Sense Organs, University of Bari, Bari, Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Romano
authors.affiliation: Department of Neuroscience and Sense Organs, University of Bari, Bari, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: Masellis
authors.affiliation: Department of Neuroscience and Sense Organs, University of Bari, Bari, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Ursini
authors.affiliation: Department of Neuroscience and Sense Organs, University of Bari, Bari, Italy.
authors.forename: Grazia
authors.initials: G
authors.lastname: Caforio
authors.affiliation: Department of Neuroscience and Sense Organs, University of Bari, Bari, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Blasi
authors.affiliation: Medical Genetics Section, Centre for Genomic and Experimental Medicine, Medical Research Council Institute of Genetics and Molecular Medicine, The University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: J Kirsty
authors.initials: JK
authors.lastname: Millar
authors.affiliation: Medical Genetics Section, Centre for Genomic and Experimental Medicine, Medical Research Council Institute of Genetics and Molecular Medicine, The University of Edinburgh, Edinburgh, United Kingdom; Centre for Cognitive Ageing and Cognitive Epidemiology, Medical Genetics Section, Centre for Genomic and Experimental Medicine, Medical Research Council Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: David John
authors.initials: DJ
authors.lastname: Porteous
authors.affiliation: Medical Genetics Section, Centre for Genomic and Experimental Medicine, Medical Research Council Institute of Genetics and Molecular Medicine, The University of Edinburgh, Edinburgh, United Kingdom; Centre for Cognitive Ageing and Cognitive Epidemiology, Medical Genetics Section, Centre for Genomic and Experimental Medicine, Medical Research Council Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Pippa Ann
authors.initials: PA
authors.lastname: Thomson
authors.affiliation: Department of Neuroscience and Sense Organs, University of Bari, Bari, Italy; Imaging, Pharma Research and Early Development, Neuroscience Discovery and Translational Area, Hoffman-La Roche, Basel, Switzerland.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Bertolino
authors.affiliation: Medical Genetics Section, Centre for Genomic and Experimental Medicine, Medical Research Council Institute of Genetics and Molecular Medicine, The University of Edinburgh, Edinburgh, United Kingdom; Centre for Cognitive Ageing and Cognitive Epidemiology, Medical Genetics Section, Centre for Genomic and Experimental Medicine, Medical Research Council Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Kathryn Louise
authors.initials: KL
authors.lastname: Evans
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D003071:Cognition; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D017397:Prefrontal Cortex / Q000503:physiopathology; D025341:Principal Component Analysis; D011485:Protein Binding; D012559:Schizophrenia / Q000235:genetics* / Q000503:physiopathology*
chemical_list: C412476:DISC1 protein, human; D009419:Nerve Tissue Proteins