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Genetic variation in neuregulin1 is associated with differences in prefrontal engagement in children

Authors

  • Andrea Mechelli,

    Corresponding author
    1. Department of Psychology, Institute of Psychiatry, King's College London, London, United Kingdom
    2. Division of Psychological Medicine and Psychiatry, Institute of Psychiatry, King's College London, London, United Kingdom
    • PO BOX 67, Institute of Psychiatry, King's College London, 103 Denmark Hill, London SE5 8AF, United Kingdom
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  • Essi Viding,

    1. Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London, United Kingdom
    2. Division of Psychology and Language Sciences, University College London, London, United Kingdom
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  • William Pettersson-Yeo,

    1. Division of Psychological Medicine and Psychiatry, Institute of Psychiatry, King's College London, London, United Kingdom
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  • Stefania Tognin,

    1. Division of Psychological Medicine and Psychiatry, Institute of Psychiatry, King's College London, London, United Kingdom
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  • Philip K. McGuire

    1. Division of Psychological Medicine and Psychiatry, Institute of Psychiatry, King's College London, London, United Kingdom
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  • This article was published online on 19 May 2009. An error was subsequently identified. This notice is included in the online and print versions to indicate that both have been corrected on 29 September 2009.

Abstract

The majority of psychopathology is rooted early in life and first emerges during childhood and adolescence. However, little is known about how risk genes affect brain function to increase biological vulnerability to psychopathology in childhood, because most imaging genetic studies published so far have been conducted on adult participants. We examined the impact of neuregulin1 (NRG1), a probable susceptibility gene for schizophrenia and bipolar disorder, on brain function in a sample of 102 ten- to twelve-year-old children. Each participant performed a Go/Nogo task, whereas brain responses were measured using functional magnetic resonance imaging. Statistical parametric mapping was used to estimate the impact of genetic variation in NRG1 on brain activation. Response accuracy and reaction times did not differ as a function of NRG1 genotype. However, individuals with the high-risk variant expressed greater brain activation for both Go and Nogo stimuli in the right posterior orbital gyrus, where NRG1 genotype accounted for 11% of interindividual variance. There were no regions showing a significant interaction between NRG1 genotype and stimulus type even at trend level, suggesting that the impact of NRG1 on brain activation was not specific to either response inhibition or motor execution. These results suggest that that genetic variation in NRG1 is associated with different levels of prefrontal engagement in children as young as 10–12 years of age. Our investigation provides support to the idea that genetic factors may affect brain function to moderate vulnerability to psychopathology from childhood. Hum Brain Mapp, 2009. © 2009 Wiley-Liss, Inc.

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