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

doi:10.1371/journal.pone.0099892

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

IRCCS Casa Sollievo della Sofferenza

Research output: Contribution to journal › Article › peer-review

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 language	English
Article number	e99892
Journal	PLoS One
Volume	9
Issue number	6
DOIs	https://doi.org/10.1371/journal.pone.0099892
Publication status	Published - Jun 18 2014

ASJC Scopus subject areas

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

Access to Document

10.1371/journal.pone.0099892

Cite this

Rampino, A., Walker, R. M., Torrance, H. S., Anderson, S. M., Fazio, L., Di Giorgio, A., Taurisano, P., Gelao, B., Romano, R., Masellis, R., Ursini, G., Caforio, G., Blasi, G., Millar, J. K., Porteous, D. J., Thomson, P. A., Bertolino, 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

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

@article{9bc90086807047c2a3c25c58602782ee,

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.",

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

year = "2014",

month = jun,

day = "18",

doi = "10.1371/journal.pone.0099892",

language = "English",

volume = "9",

journal = "PLoS One",

issn = "1932-6203",

publisher = "Public Library of Science",

number = "6",

}

TY - JOUR

T1 - Expression of DISC1-interactome members correlates with cognitive phenotypes related to schizophrenia

AU - Rampino, Antonio

AU - Walker, Rosie May

AU - Torrance, Helen Scott

AU - Anderson, Susan Maguire

AU - Fazio, Leonardo

AU - Di Giorgio, Annabella

AU - Taurisano, Paolo

AU - Gelao, Barbara

AU - Romano, Raffaella

AU - Masellis, Rita

AU - Ursini, Gianluca

AU - Caforio, Grazia

AU - Blasi, Giuseppe

AU - Millar, J. Kirsty

AU - Porteous, David John

AU - Thomson, Pippa Ann

AU - Bertolino, Alessandro

AU - Evans, Kathryn Louise

PY - 2014/6/18

Y1 - 2014/6/18

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84903291833&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84903291833&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0099892

DO - 10.1371/journal.pone.0099892

M3 - Article

C2 - 24940743

AN - SCOPUS:84903291833

VL - 9

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 6

M1 - e99892

ER -

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

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this