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A neuregulin 1 variant associated with abnormal cortical function and psychotic symptoms

Nature Neuroscience 9, 1477–1478 (2006) | Download Citation

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Abstract

NRG1, encoding neuregulin 1, is a susceptibility gene for schizophrenia, but no functional mutation causally related to the disorder has yet been identified. Here we investigate the effects of a variant in the human NRG1 promoter region in subjects at high risk of schizophrenia. We show that this variant is associated with (i) decreased activation of frontal and temporal lobe regions, (ii) increased development of psychotic symptoms and (iii) decreased premorbid IQ.

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Acknowledgements

We thank P. Miller for assistance with data management. This work was funded by the Dr Mortimer and Theresa Sackler Institute Foundation, the UK Medical Research Council (Programme Grants G9226254 and G9825423 awarded to E.C.J. and colleagues, and G0100266 awarded to D.J.P. and colleagues) and the Stanley Medical Research Institute (for support of B.J.B). Imaging was conducted at the Scottish Higher Education Funding Council Brain Imaging Research Centre, Edinburgh. Genotyping was performed at the Wellcome Trust Clinical Research Facility Genetics Core.

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Affiliations

  1. Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Morningside Park, Edinburgh, EH10 5HF, UK.

    • Jeremy Hall
    • , Heather C Whalley
    • , Dominic E Job
    • , Ben J Baig
    • , Andrew M McIntosh
    • , David G Cunningham-Owens
    • , Eve C Johnstone
    •  & Stephen M Lawrie

  2. Section of Medical Genetics, University of Edinburgh, Molecular Medicine Centre, Western General Hospital, Crewe Road, Edinburgh, EH4 2XU, UK.

    • Kathryn L Evans
    • , Pippa A Thomson
    •  & David J Porteous

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Contributions

J.H. investigated the association of NRG1 with psychotic symptoms in this cohort and wrote the manuscript. H.C.W. and J.H. conducted the fMRI analysis. D.E.J. conducted the structural MRI analysis. B.J.B. collected the blood samples and A.M.M. gave advice regarding data analysis. K.L.E. and P.A.T. contributed to the analysis of the genetic data and D.J.P. supervised the genetic component of the project. E.C.J. designed and implemented the project. D.G.C.-O. and E.C.J. conducted the clinical assessments. S.M.L. supervised the neuroimaging.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Jeremy Hall.

Supplementary information

PDF files

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    Supplementary Fig. 1

    Graphs represent parameter estimates and 90% confidence intervals for the 3 genotype groups in the contrast of sentence completion versus rest at peak voxels in medial prefrontal cortext and right temporo-occipital junction.

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    Supplementary Table 1

    Additional marker information.

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    Supplementary Table 2

    Symptom severity.

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    Supplementary Table 3

    Symptom type.

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    Supplementary Table 4

    fMRI data excluding related subjects.

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    Supplementary Methods

  7. 7.

    Supplementary Note

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DOI

https://doi.org/10.1038/nn1795

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