Expression of DISC1-interactome members correlates with cognitive phenotypes related to schizophrenia

Antonio Rampino, Rosie May Walker, Helen Scott Torrance, Susan Maguire Anderson, Leonardo Fazio, Annabella Di Giorgio, Paolo Taurisano, Barbara Gelao, Raffaella Romano, Rita Masellis, Gianluca Ursini, Grazia Caforio, Giuseppe Blasi, J. Kirsty Millar, David John Porteous, Pippa Ann Thomson, Alessandro Bertolino, Kathryn Louise Evans

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article numbere99892
JournalPLoS One
Volume9
Issue number6
DOIs
StatePublished - Jun 18 2014
Externally publishedYes

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Schizophrenia
Phenotype
phenotype
Genes
cognition
Cognition
Gene expression
Blood
schizophrenia
Brain
Prefrontal Cortex
RNA
Data storage equipment
genes
Gene Expression
gene expression
Proteins
blood
Short-Term Memory
magnetic resonance imaging

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Rampino, A., Walker, R. M., Torrance, H. S., Anderson, S. M., Fazio, L., Di Giorgio, A., ... Evans, K. L. (2014). Expression of DISC1-interactome members correlates with cognitive phenotypes related to schizophrenia. PLoS One, 9(6), [e99892]. https://doi.org/10.1371/journal.pone.0099892

Expression of DISC1-interactome members correlates with cognitive phenotypes related to schizophrenia. / Rampino, Antonio; Walker, Rosie May; Torrance, Helen Scott; Anderson, Susan Maguire; Fazio, Leonardo; Di Giorgio, Annabella; Taurisano, Paolo; Gelao, Barbara; Romano, Raffaella; Masellis, Rita; Ursini, Gianluca; Caforio, Grazia; Blasi, Giuseppe; Millar, J. Kirsty; Porteous, David John; Thomson, Pippa Ann; Bertolino, Alessandro; Evans, Kathryn Louise.

In: PLoS One, Vol. 9, No. 6, e99892, 18.06.2014.

Research output: Contribution to journalArticle

Rampino, A, Walker, RM, Torrance, HS, Anderson, SM, Fazio, L, Di Giorgio, A, Taurisano, P, Gelao, B, Romano, R, Masellis, R, Ursini, G, Caforio, G, Blasi, G, Millar, JK, Porteous, DJ, Thomson, PA, Bertolino, A & Evans, KL 2014, 'Expression of DISC1-interactome members correlates with cognitive phenotypes related to schizophrenia', PLoS One, vol. 9, no. 6, e99892. https://doi.org/10.1371/journal.pone.0099892
Rampino A, Walker RM, Torrance HS, Anderson SM, Fazio L, Di Giorgio A et al. Expression of DISC1-interactome members correlates with cognitive phenotypes related to schizophrenia. PLoS One. 2014 Jun 18;9(6). e99892. https://doi.org/10.1371/journal.pone.0099892
Rampino, Antonio ; Walker, Rosie May ; Torrance, Helen Scott ; Anderson, Susan Maguire ; Fazio, Leonardo ; Di Giorgio, Annabella ; Taurisano, Paolo ; Gelao, Barbara ; Romano, Raffaella ; Masellis, Rita ; Ursini, Gianluca ; Caforio, Grazia ; Blasi, Giuseppe ; Millar, J. Kirsty ; Porteous, David John ; Thomson, Pippa Ann ; Bertolino, Alessandro ; Evans, Kathryn Louise. / Expression of DISC1-interactome members correlates with cognitive phenotypes related to schizophrenia. In: PLoS One. 2014 ; Vol. 9, No. 6.
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AU - Millar, J. Kirsty

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