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    The association of white matter volume in psychotic disorders with genotypic variation in NRG1, MOG and CNP: a voxel-based analysis in affected individuals and their unaffected relatives.

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    Author
    Cannon, DM; Walshe, M; Dempster, E; Collier, DA; Marshall, N; Bramon, E; Murray, RM; McDonald, C
    Date
    2012-10-09
    Source Title
    Translational Psychiatry
    Publisher
    Springer Science and Business Media LLC
    University of Melbourne Author/s
    Murray, Robin
    Affiliation
    Medical Education
    Metadata
    Show full item record
    Document Type
    Journal Article
    Citations
    Cannon, D. M., Walshe, M., Dempster, E., Collier, D. A., Marshall, N., Bramon, E., Murray, R. M. & McDonald, C. (2012). The association of white matter volume in psychotic disorders with genotypic variation in NRG1, MOG and CNP: a voxel-based analysis in affected individuals and their unaffected relatives.. Transl Psychiatry, 2 (10), pp.e167-. https://doi.org/10.1038/tp.2012.82.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/255219
    DOI
    10.1038/tp.2012.82
    Open Access at PMC
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3565820
    Abstract
    We investigated the role of variation in putative psychosis genes coding for elements of the white matter system by examining the contribution of genotypic variation in three single-nucleotide polymorphisms (SNPs) neuregulin 1 (NRG1) SNP8NRG221533, myelin oligodendrocytes glycoprotein (MOG) rs2857766 and CNP (rs2070106) and one haplotype HAP(ICE) (deCODE) to white matter volume in patients with psychotic disorder and their unaffected relatives. Structural magnetic resonance imaging and blood samples for genotyping were collected on 189 participants including patients with schizophrenia (SZ) or bipolar I disorder (BDI), unaffected first-degree relatives of these patients and healthy volunteers. The association of genotypic variation with white matter volume was assessed using voxel-based morphometry in SPM5. The NRG1 SNP and the HAP(ICE) haplotype were associated with abnormal white matter volume in the BDI group in the fornix, cingulum and parahippocampal gyrus circuit. In SZ the NRG1 SNP risk allele was associated with lower white matter volume in the uncinate fasciculus (UF), right inferior longitudinal fasciculus and the anterior limb of the internal capsule. Healthy G-homozygotes of the MOG SNP had greater white matter volume in areas of the brainstem and cerebellum; this relationship was absent in those with a psychotic disorder and the unaffected relatives groups. The CNP SNP did not contribute to white matter volume variation in the diagnostic groups studied. Variation in the genes coding for structural and protective components of myelin are implicated in abnormal white matter volume in the emotion circuitry of the cingulum, fornix, parahippocampal gyrus and UF in psychotic disorders.

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