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The effects of a neuregulin 1 variant on white matter density and integrity

McIntosh, A. M., Moorhead, T. W. J., Job, D., Lymer, G. K. S., Muñoz Maniega, S., McKirdy, J., Sussmann, J. E. D., Baig, B. J., Bastin, M. E., Porteous, D., Evans, K., Johnstone, E. C., Lawrie, S. M. and Hall, Jeremy 2008. The effects of a neuregulin 1 variant on white matter density and integrity. Molecular Psychiatry 13 (11) , pp. 1054-1059. 10.1038/sj.mp.4002103

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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 (T1-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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Medicine
Subjects: R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Uncontrolled Keywords: schizophrenia; bipolar disorder; MRI; tensor-based morphometry; cohort study
Publisher: Nature Publishing Group
ISSN: 1359-4184
Last Modified: 04 Jun 2017 04:56
URI: http://orca.cf.ac.uk/id/eprint/46521

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