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Common variation in NCAN, a risk factor for bipolar disorder and schizophrenia, influences local cortical folding in schizophrenia

Published online by Cambridge University Press:  24 June 2013

C. C. Schultz*
Affiliation:
Department of Psychiatry and Psychotherapy, Jena University Hospital, Germany
T. W. Mühleisen
Affiliation:
Institute of Human Genetics, University of Bonn, Germany Department of Genomics, Life and Brain Centre, University of Bonn, Germany Institute of Neuroscience and Medicine (INM-1), Research Centre Juelich, Germany
I. Nenadic
Affiliation:
Department of Psychiatry and Psychotherapy, Jena University Hospital, Germany
K. Koch
Affiliation:
Department of Psychiatry and Psychotherapy, Jena University Hospital, Germany Department of Neuroradiology, Klinikum rechts der Isar, Technische Universität München, Germany
G. Wagner
Affiliation:
Department of Psychiatry and Psychotherapy, Jena University Hospital, Germany
C. Schachtzabel
Affiliation:
Department of Psychiatry and Psychotherapy, Jena University Hospital, Germany
F. Siedek
Affiliation:
Institute of Human Genetics, University of Bonn, Germany Department of Genomics, Life and Brain Centre, University of Bonn, Germany
M. M. Nöthen
Affiliation:
Institute of Human Genetics, University of Bonn, Germany Department of Genomics, Life and Brain Centre, University of Bonn, Germany German Centre for Neurodegenerative Diseases (DZNE), Bonn, Germany
M. Rietschel
Affiliation:
Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Germany
T. Deufel
Affiliation:
Department of Clinical Chemistry and Laboratory Diagnostics, Jena University Hospital, Germany
M. Kiehntopf
Affiliation:
Department of Clinical Chemistry and Laboratory Diagnostics, Jena University Hospital, Germany
S. Cichon
Affiliation:
Institute of Human Genetics, University of Bonn, Germany Department of Genomics, Life and Brain Centre, University of Bonn, Germany Institute of Neuroscience and Medicine (INM-1), Research Centre Juelich, Germany Division of Medical Genetics, University of Basel, Switzerland
J. R. Reichenbach
Affiliation:
Medical Physics Group, Institute for Diagnostic and Interventional Radiology I, Jena University Hospital, Germany
H. Sauer
Affiliation:
Department of Psychiatry and Psychotherapy, Jena University Hospital, Germany
R. G. M. Schlösser
Affiliation:
Department of Psychiatry and Psychotherapy, Jena University Hospital, Germany
*
*Address for correspondence: C. C. Schultz, M.D., Department of Psychiatry and Psychotherapy, Jena University Hospital, Philosophenweg 3, 07740 Jena, Germany. (Email: christoph.schultz@med.uni-jena.de)

Abstract

Background

Recent studies have provided strong evidence that variation in the gene neurocan (NCAN, rs1064395) is a common risk factor for bipolar disorder (BD) and schizophrenia. However, the possible relevance of NCAN variation to disease mechanisms in the human brain has not yet been explored. Thus, to identify a putative pathomechanism, we tested whether the risk allele has an influence on cortical thickness and folding in a well-characterized sample of patients with schizophrenia and healthy controls.

Method

Sixty-three patients and 65 controls underwent T1-weighted magnetic resonance imaging (MRI) and were genotyped for the single nucleotide polymorphism (SNP) rs1064395. Folding and thickness were analysed on a node-by-node basis using a surface-based approach (FreeSurfer).

Results

In patients, NCAN risk status (defined by AA and AG carriers) was found to be associated with higher folding in the right lateral occipital region and at a trend level for the left dorsolateral prefrontal cortex. Controls did not show any association (p > 0.05). For cortical thickness, there was no significant effect in either patients or controls.

Conclusions

This study is the first to describe an effect of the NCAN risk variant on brain structure. Our data show that the NCAN risk allele influences cortical folding in the occipital and prefrontal cortex, which may establish disease susceptibility during neurodevelopment. The findings suggest that NCAN is involved in visual processing and top-down cognitive functioning. Both major cognitive processes are known to be disturbed in schizophrenia. Moreover, our study reveals new evidence for a specific genetic influence on local cortical folding in schizophrenia.

Type
Original Articles
Copyright
Copyright © Cambridge University Press 2013 

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Common variation in NCAN, a risk factor for bipolar disorder and schizophrenia, influences local cortical folding in schizophrenia
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Common variation in NCAN, a risk factor for bipolar disorder and schizophrenia, influences local cortical folding in schizophrenia
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Common variation in NCAN, a risk factor for bipolar disorder and schizophrenia, influences local cortical folding in schizophrenia
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