DISC1 is associated with cortical thickness and neural efficiency

Stefan Brauns; Randy L Gollub; Joshua L Roffman; Anastasia Yendiki; Beng-Choon Ho; Thomas H Wassink; Andreas Heinz; Stefan Ehrlich

doi:10.1016/j.neuroimage.2011.05.058

Back

DISC1 is associated with cortical thickness and neural efficiency

Journal article

Peer reviewed

DISC1 is associated with cortical thickness and neural efficiency

Stefan Brauns, Randy L Gollub, Joshua L Roffman, Anastasia Yendiki, Beng-Choon Ho, Thomas H Wassink, Andreas Heinz and Stefan Ehrlich

NeuroImage (Orlando, Fla.), Vol.57(4), pp.1591-1600

08/15/2011

DOI: 10.1016/j.neuroimage.2011.05.058

PMCID: PMC3138880

PMID: 21642004

View Online

Abstract

Disrupted in schizophrenia 1 (DISC1) is known to play a major role during brain development and is a candidate gene for schizophrenia. Cortical thickness is highly heritable and several MRI studies have shown widespread reductions of cortical thickness in patients with schizophrenia. Here, we investigated the effects of variation in DISC1 on cortical thickness. In a subsequent analysis we tested whether the identified DISC1 risk variant is also associated with neural activity during working memory functioning. We acquired structural MRI (sMRI), functional MRI (fMRI) and genotype data from 96 healthy volunteers. Separate cortical statistical maps for five single nucleotide polymorphisms (SNP) of DISC1 were generated to detect differences of cortical thickness in genotype groups across the entire cortical surface. Working-memory related load-dependent activation was measured during the Sternberg Item Recognition Paradigm and analyzed using a region-of-interest approach. Phe allele carriers of the DISC1 SNP Leu607Phe had significantly reduced cortical thickness in the left supramarginal gyrus compared to Leu/Leu homozygotes. Neural activity in the left dorsolateral prefrontal cortex (DLPFC) during working memory task was increased in Phe allele carriers, whereas working memory performance did not differ between genotype groups. This study provides convergent evidence for the effect of DISC1 risk variants on two independent brain-based intermediate phenotypes of schizophrenia. The same risk variant was associated with cortical thickness reductions and signs of neural inefficiency during a working memory task. Our findings provide further evidence for a neurodevelopmental model of schizophrenia. ► We examine effects of variation in DISC1 on cortical thickness and neural efficiency. ► Phe allele carriers of the DISC1 SNP Leu607Phe have reduced cortical thickness. ► Neural activity during working memory task was increased in Phe allele carriers. ► Working memory performance did not differ within Leu607Phe genotype groups. ► The Phe allele is associated with neural inefficiency during a working memory task.

Schizophrenia

Functional MRI

Cortical thickness

Single nucleotide polymorphism

Working memory

DISC1

Details

Title: Subtitle: DISC1 is associated with cortical thickness and neural efficiency
Creators: Stefan Brauns - MGH/MIT/HMS Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, USA
Randy L Gollub - MGH/MIT/HMS Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, USA
Joshua L Roffman - MGH/MIT/HMS Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, USA
Anastasia Yendiki - MGH/MIT/HMS Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, USA
Beng-Choon Ho - Department of Psychiatry, University of Iowa, Iowa City, IA, USA
Thomas H Wassink - Department of Psychiatry, University of Iowa, Iowa City, IA, USA
Andreas Heinz - Department of Psychiatry, Charité, Universitätsmedizin Berlin, Germany
Stefan Ehrlich - MGH/MIT/HMS Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, USA
Resource Type: Journal article
Publication Details: NeuroImage (Orlando, Fla.), Vol.57(4), pp.1591-1600
DOI: 10.1016/j.neuroimage.2011.05.058
PMID: 21642004
PMCID: PMC3138880
NLM abbreviation: Neuroimage
ISSN: 1053-8119
eISSN: 1095-9572
Publisher: Elsevier Inc
Grant note: name: NIH/NCRR, award: P41RR14075, MO1 RR025758-01; DOI: 10.13039/100000015, name: Department of Energy, award: DE-FG02-99ER62764; name: MIND Research Network; name: Morphometry BIRN, award: 1U24, RR021382A; name: Function BIRN, award: U24RR021992-01; DOI: 10.13039/501100001659, name: Deutsche Forschungsgemeinschaft; name: Biomedical Science Exchange Program
Language: English
Date published: 08/15/2011
Academic Unit: Psychiatry; Stead Family Department of Pediatrics
Record Identifier: 9984003950102771

Metrics

26 Record Views

41 Times Cited - Web of Science