title: The effects of a neuregulin 1 variant on white matter density and integrity.
abstract: Theories of abnormal anatomical and functional connectivity in schizophrenia and bipolar disorder are supported by evidence from functional magnetic resonance imaging (MRI), structural MRI and diffusion tensor imaging (DTI). The presence of similar abnormalities in unaffected relatives suggests such disconnectivity is genetically mediated, albeit through unspecified loci. Neuregulin 1 (NRG1) is a psychosis susceptibility gene with effects on neuronal migration, axon guidance and myelination that could potentially explain these findings. In the current study, unaffected subjects were genotyped at the NRG1 single nucleotide polymorphism (SNP) rs6994992 (SNP8NRG243177) locus, previously associated with increased risk for psychosis, and the effect of genetic variation at this locus on white matter density (T(1)-weighted MRI) and integrity (DTI) was ascertained. Subjects with the risk-associated TT genotype had reduced white matter density in the anterior limb of the internal capsule and evidence of reduced structural connectivity in the same region using DTI. We therefore provide the first imaging evidence that genetic variation in NRG1 is associated with reduced white matter density and integrity in human subjects. This finding is discussed in the context of NRG1 effects on neuronal migration, axon guidance and myelination.
authors.affiliation: Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, UK. andrew.mcintosh@ed.ac.uk
authors.forename: A M
authors.initials: AM
authors.lastname: McIntosh
authors.forename: T W J
authors.initials: TW
authors.lastname: Moorhead
authors.forename: D
authors.initials: D
authors.lastname: Job
authors.forename: G K S
authors.initials: GK
authors.lastname: Lymer
authors.forename: S
authors.initials: S
authors.lastname: Muñoz Maniega
authors.forename: J
authors.initials: J
authors.lastname: McKirdy
authors.forename: J E D
authors.initials: JE
authors.lastname: Sussmann
authors.forename: B J
authors.initials: BJ
authors.lastname: Baig
authors.forename: M E
authors.initials: ME
authors.lastname: Bastin
authors.forename: D
authors.initials: D
authors.lastname: Porteous
authors.forename: K L
authors.initials: KL
authors.lastname: Evans
authors.forename: E C
authors.initials: EC
authors.lastname: Johnstone
authors.forename: S M
authors.initials: SM
authors.lastname: Lawrie
authors.forename: J
authors.initials: J
authors.lastname: Hall
mesh_terms: D001921:Brain / Q000033:anatomy & histology*; D001931:Brain Mapping; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009434:Neural Pathways / Q000033:anatomy & histology; D020890:Neuregulin-1; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
chemical_list: C094131:NRG1 protein, human; D009419:Nerve Tissue Proteins; D020890:Neuregulin-1