title: Neurexin-1 and frontal lobe white matter: an overlapping intermediate phenotype for schizophrenia and autism spectrum disorders.
abstract: BACKGROUND
  Structural variation in the neurexin-1 (NRXN1) gene increases risk for both autism spectrum disorders (ASD) and schizophrenia. However, the manner in which NRXN1 gene variation may be related to brain morphology to confer risk for ASD or schizophrenia is unknown.
  
  
  RESULTS
  53 healthy individuals between 18-59 years of age were genotyped at 11 single nucleotide polymorphisms of the NRXN1 gene. All subjects received structural MRI scans, which were processed to determine cortical gray and white matter lobar volumes, and volumes of striatal and thalamic structures. Each subject's sensorimotor function was also assessed. The general linear model was used to calculate the influence of genetic variation on neural and cognitive phenotypes. Finally, in silico analysis was conducted to assess potential functional relevance of any polymorphisms associated with brain measures. A polymorphism located in the 3' untranslated region of NRXN1 significantly influenced white matter volumes in whole brain and frontal lobes after correcting for total brain volume, age and multiple comparisons. Follow-up in silico analysis revealed that this SNP is a putative microRNA binding site that may be of functional significance in regulating NRXN1 expression. This variant also influenced sensorimotor performance, a neurocognitive function impaired in both ASD and schizophrenia.
  
  
  CONCLUSIONS
  Our findings demonstrate that the NRXN1 gene, a vulnerability gene for SCZ and ASD, influences brain structure and cognitive function susceptible in both disorders. In conjunction with our in silico results, our findings provide evidence for a neural and cognitive susceptibility mechanism by which the NRXN1 gene confers risk for both schizophrenia and ASD.
authors.affiliation: Centre for Addiction and Mental Health, University of Toronto, Toronto, Canada. Aristotle_Voineskos@camh.net
authors.forename: Aristotle N
authors.initials: AN
authors.lastname: Voineskos
authors.forename: Tristram A P
authors.initials: TA
authors.lastname: Lett
authors.forename: Jason P
authors.initials: JP
authors.lastname: Lerch
authors.forename: Arun K
authors.initials: AK
authors.lastname: Tiwari
authors.forename: Stephanie H
authors.initials: SH
authors.lastname: Ameis
authors.forename: Tarek K
authors.initials: TK
authors.lastname: Rajji
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Müller
authors.forename: Benoit H
authors.initials: BH
authors.lastname: Mulsant
authors.forename: James L
authors.initials: JL
authors.lastname: Kennedy
mesh_terms: D000328:Adult; D002135:Calcium-Binding Proteins; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics*; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000235:genetics* / Q000503:physiopathology; D003071:Cognition; D019295:Computational Biology; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D019006:Neural Cell Adhesion Molecules; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics* / Q000503:physiopathology; D055815:Young Adult
chemical_list: D002135:Calcium-Binding Proteins; D015816:Cell Adhesion Molecules, Neuronal; C539628:NRXN1 protein, human; D009419:Nerve Tissue Proteins; D019006:Neural Cell Adhesion Molecules