title: Dysbindin modulates brain function during visual processing in children.
abstract: 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 function is poorly understood. It has been proposed that DTNBP1 may be associated with differences in visual processing. To test this, we examined the impact on visual processing in 61 healthy children aged 10-12 years of a genetic variant in DTNBP1 (rs2619538) that was common to all schizophrenia associated haplotypes in an earlier UK-Irish study. We tested the hypothesis that carriers of the risk allele would show altered occipital cortical function relative to noncarriers. Functional Magnetic Resonance Imaging (fMRI) was used to measure brain responses during a visual matching task. The data were analysed using statistical parametric mapping and statistical inferences were made at p<0.05 (corrected for multiple comparisons). Relative to noncarriers, carriers of the risk allele had greater activation in the lingual, fusiform gyrus and inferior occipital gyri. In these regions DTNBP1 genotype accounted for 19%, 20% and 14% of the inter-individual variance, respectively. Our results suggest that that genetic variation in DTNBP1 is associated with differences in the function of brain areas that mediate visual processing, and that these effects are evident in young children. These findings are consistent with the notion that the DTNBP1 gene influences brain development and can thereby modulate vulnerability to schizophrenia.
authors.affiliation: Department of Psychology, Institute of Psychiatry, King's College London, 103 Denmark Hill, London, UK. a.mechelli@iop.kcl.ac.uk
authors.forename: A
authors.initials: A
authors.lastname: Mechelli
authors.forename: E
authors.initials: E
authors.lastname: Viding
authors.forename: A
authors.initials: A
authors.lastname: Kumar
authors.forename: W
authors.initials: W
authors.lastname: Pettersson-Yeo
authors.forename: P
authors.initials: P
authors.lastname: Fusar-Poli
authors.forename: S
authors.initials: S
authors.lastname: Tognin
authors.forename: M C
authors.initials: MC
authors.lastname: O'Donovan
authors.forename: P
authors.initials: P
authors.lastname: McGuire
mesh_terms: D000483:Alleles; D001921:Brain / Q000502:physiology*; D002352:Carrier Proteins / Q000235:genetics* / Q000502:physiology*; D002648:Child; D003071:Cognition / Q000502:physiology; D004247:DNA / Q000235:genetics; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins; D015870:Gene Expression / Q000502:physiology; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D009483:Neuropsychological Tests; D009778:Occipital Lobe / Q000378:metabolism / Q000502:physiology; D020641:Polymorphism, Single Nucleotide; D011597:Psychomotor Performance / Q000502:physiology; D012306:Risk; D012559:Schizophrenia / Q000235:genetics; D012565:Schizophrenic Psychology; D014796:Visual Perception / Q000235:genetics* / Q000502:physiology*
chemical_list: D002352:Carrier Proteins; C432416:DTNBP1 protein, human; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins; D004247:DNA