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A GRIK4 variant conferring protection against bipolar disorder modulates hippocampal function

Molecular Psychiatry volume 14, pages 467–468 (2009)Cite this article

The GRIK4 gene encodes the kainate glutamate receptor subunit, KA1, which is expressed at high levels in the hippocampus.1, 2 Cytogenetic and associated studies have shown that genetic variation in GRIK4 alters risk for bipolar disorder and schizophrenia.3 Recently a common insertion–deletion (indel) variant was identified in the 3′ untranslated region (3′UTR) of the GRIK4 gene, which alters GRIK4 expression in the hippocampus and confers protection against bipolar disorder.4 Here we show that the same GRIK4 variant modulates hippocampal activity as assessed by functional magnetic resonance imaging.

Forty-two unrelated healthy Caucasian participants with no personal or family history of major mental illness completed a functional magnetic resonance imaging facial affect-processing task. In this task, subjects view blocks of faces, which either have a neutral or fearful facial expression and interspersed blocks of a baseline fixation condition5 (Supplementary Methods). Extensive activation of medial temporal lobe regions, including the hippocampus, is seen during face processing compared with a baseline fixation condition (Supplementary Figure 1). In addition, there is a modulatory effect of emotion in the task with greater amygdala activation elicited during the viewing of fearful faces than the neutral ones.5

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References

  1. Lerma J . Curr Opin Pharmacol 2006; 6: 89.

    Article  CAS  Google Scholar 

  2. Darstein M, Petralia RS, Swanson GT, Wenthold RJ, Heinemann SF . J Neurosci 2003; 23: 8013–8019.

    Article  CAS  Google Scholar 

  3. Pickard BS, Malloy MP, Christoforou A, Thomson PA, Evans KL, Morris SW et al. Mol Psychiatry 2006; 11: 847–857.

    Article  CAS  Google Scholar 

  4. Pickard BS, Knight HM, Hamilton RS, Soares DC, Walker R, Boyd JKF et al. Proc Natl Acad Sci USA 2008; 105: 14940–14945.

    Article  CAS  Google Scholar 

  5. Hall J, Whalley HC, McKirdy JW, Romaniuk L, McGonigle D, McIntosh AM et al. Biol Psychiatry 2008; 64: 70–73.

    Article  Google Scholar 

  6. Porter RHP, Eastwood SL, Harrison PJ . Brain Res 1997; 751: 217–231.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Division of Psychiatry, University of Edinburgh, Kennedy Tower, Royal Edinburgh Hospital, Edinburgh, UK

    H C Whalley, A M McIntosh, E C Johnstone, D H R Blackwood, S M Lawrie, W J Muir & J Hall

  2. Medical Genetics, Institute for Genetics and Molecular Medicine, University of Edinburgh, Molecular Medicine Centre, Western General Hospital, Edinburgh, UK

    B S Pickard

  3. Clinica di Psichiatria, Psicologia Medica e Psicosomatica, DPMSC, University of Udine, Udine, Italy

    R Zuliani

Authors
  1. H C Whalley
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  2. B S Pickard
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  3. A M McIntosh
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  4. R Zuliani
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  5. E C Johnstone
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  6. D H R Blackwood
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  7. S M Lawrie
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  8. W J Muir
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  9. J Hall
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Corresponding author

Correspondence to J Hall.

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Supplementary Information accompanies the paper on the Molecular Psychiatry website (http://www.nature.com/mp)

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Whalley, H., Pickard, B., McIntosh, A. et al. A GRIK4 variant conferring protection against bipolar disorder modulates hippocampal function. Mol Psychiatry 14, 467–468 (2009). https://doi.org/10.1038/mp.2009.7

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