title: DISC1 is associated with cortical thickness and neural efficiency.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: MGH/MIT/HMS Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA 02129-2000, USA.
authors.forename: Stefan
authors.initials: S
authors.lastname: Brauns
authors.forename: Randy L
authors.initials: RL
authors.lastname: Gollub
authors.forename: Joshua L
authors.initials: JL
authors.lastname: Roffman
authors.forename: Anastasia
authors.initials: A
authors.lastname: Yendiki
authors.forename: Beng-Choon
authors.initials: BC
authors.lastname: Ho
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Wassink
authors.forename: Andreas
authors.initials: A
authors.lastname: Heinz
authors.forename: Stefan
authors.initials: S
authors.lastname: Ehrlich
mesh_terms: D000328:Adult; D001931:Brain Mapping; D002540:Cerebral Cortex / Q000473:pathology* / Q000503:physiopathology; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008570:Memory, Short-Term / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012559:Schizophrenia / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology
chemical_list: C412476:DISC1 protein, human; D009419:Nerve Tissue Proteins