title: Effects of DTNBP1 genotype on brain development in children.
abstract: BACKGROUND
  Schizophrenia is a neurodevelopmental disorder, and risk genes are thought to act through disruption of brain development. Several genetic studies have identified dystrobrevin-binding protein 1 (DTNBP1, also known as dysbindin) as a potential susceptibility gene for schizophrenia, but its impact on brain development is poorly understood. The present investigation examined for the first time the effects of DTNBP1 on brain structure in children. Our hypothesis was that a genetic variation in DTNBP1 (i.e., the single nucleotide polymorphism rs2619538) would be associated with differences in both gray and white matter brain regions previously implicated in schizophrenia.
  
  
  METHODS
  Magnetic resonance imaging and voxel-based morphometry were used to examine brain structure in 52 male children aged between 10 and 12 years. Statistical inferences on the effects of DTNBP1 genotype on gray and white matter volume (GMV and WMV) were made at p < .05 after family-wise error correction for multiple comparisons across the whole brain.
  
  
  RESULTS
  Individuals homozygous for the schizophrenia high-risk allele (AA) compared with those homozygous for the low-risk allele (TT) expressed reduced GMV in the left anterior cingulate gyrus and reduced WMV in the left medial frontal area.
  
  
  CONCLUSIONS
  Our results suggest that genetic variation in DTNBP1 is associated with differences in gray and white matter; and that these effects are already evident in children as young as 10-12 years. These findings are consistent with the notion that the DTNBP1 genotype influences brain development and may thereby modulate vulnerability to schizophrenia.
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, UK. stefania.tognin@kcl.ac.uk
authors.forename: Stefania
authors.initials: S
authors.lastname: Tognin
authors.forename: Essi
authors.initials: E
authors.lastname: Viding
authors.forename: Eamon J
authors.initials: EJ
authors.lastname: McCrory
authors.forename: Lauren
authors.initials: L
authors.lastname: Taylor
authors.forename: Michael C
authors.initials: MC
authors.lastname: O'Donovan
authors.forename: Philip
authors.initials: P
authors.lastname: McGuire
authors.forename: Andrea
authors.initials: A
authors.lastname: Mechelli
mesh_terms: D000483:Alleles; D001921:Brain / Q000254:growth & development* / Q000473:pathology*; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012559:Schizophrenia / Q000235:genetics* / Q000473:pathology
chemical_list: D002352:Carrier Proteins; C432416:DTNBP1 protein, human; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins