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Neuregulin 3 (NRG3) as a susceptibility gene in a schizophrenia subtype with florid delusions and relatively spared cognition

Molecular Psychiatry volume 16, pages 860–866 (2011)Cite this article

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Abstract

Linkage of 10q22-q23 to schizophrenia and the recently reported association of Neuregulin 3 (NRG3) polymorphisms with high ‘delusion factor’ scores led us to attempt replication and further refinement of these findings in a sample of 411 schizophrenic patients and 223 nonpsychiatric control subjects. Using quantitative cognitive traits, patients were grouped into a cluster with pervasive cognitive deficit (CD) and a cluster with relatively spared cognition (CS). We found a significant association between rs6584400 and schizophrenia, with a trend for rs10883866. Post hoc analysis revealed that this result was mainly due to the CS cluster, characterized by elevated scores on Schneiderian first-rank symptoms, salience of complex delusions and positive thought disorder—thus closely related to the ‘delusion factor’. In addition, both rs6584400 and rs10883866 were associated with the degraded-stimulus continuous performance task in which ‘risk’ alleles were associated with better than average performance in patients and worse performance in controls. This suggests that NRG3 may be modulating early attentional processes for perceptual sensitivity and vigilance, with opposite effects in affected individuals and healthy controls. The two single-nucleotide polymorphisms are in close proximity to the alternative first exons of the NRG3-a, -b and -d isoforms, of which the human brain-specific NRG-b appears to be the most interesting candidate.

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Acknowledgements

We thank the patients, family members and other volunteers who participated in the study and the staff of the North Metropolitan Health Area mental health services in Western Australia for assistance in patient recruitment. The study was supported by Grant #37580400 and #37580900 of the National Health and Medical Research Council of Australia to Professor A Jablensky and Professor L Kalaydjieva, with funding contribution from the North Metropolitan Health Area, Perth, Western Australia.

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Author notes

  1. L Kalaydjieva and A Jablensky: These authors contributed equally to this study.

Authors and Affiliations

  1. Centre for Medical Research/Western Australian Institute for Medical Research, The University of Western Australia, Perth, WA, Australia

    B Morar, D Chandler & L Kalaydjieva

  2. Centre for Clinical Research in Neuropsychiatry and School of Psychiatry and Clinical Neurosciences, The University of Western Australia, Perth, WA, Australia

    M Dragović, F A V Waters & A Jablensky

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  1. B Morar
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  2. M Dragović
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  3. F A V Waters
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  4. D Chandler
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  5. L Kalaydjieva
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  6. A Jablensky
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Correspondence to A Jablensky.

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The authors declare no conflict of interest.

Additional information

URLs used in this study:

http://www.cbil.upenn.edu/cgi-bin/tess/tess

http://asp.ii.uib.no:8090/cgi-bin/CONSITE/consite

http://www.umd.be/HSF/

http://www.ncbi.nlm.nih.gov/IEB/Research/Acembly/

http://genome.ucsc.edu/

http://blast.ncbi.nlm.nih.gov/Blast.cgi

http://biogps.gnf.org/#goto=welcome

http://www.spss.com/worldwide/

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Morar, B., Dragović, M., Waters, F. et al. Neuregulin 3 (NRG3) as a susceptibility gene in a schizophrenia subtype with florid delusions and relatively spared cognition. Mol Psychiatry 16, 860–866 (2011). https://doi.org/10.1038/mp.2010.70

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