Abnormal cortical activation during response inhibition in 22q11.2 deletion syndrome

Authors

  • Doron Gothelf,

    Corresponding author
    1. The Behavioral Neurogenetics Center, Child Psychiatry Department, Schneider Children's Medical Center of Israel, Petah Tiqwa, Israel
    2. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
    • Child Psychiatry Department, Schneider Children's Medical Center of Israel, 14 Kaplan St., Petah Tiqwa 49202, Israel
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  • Fumiko Hoeft,

    1. Center for Interdisciplinary Brain Sciences Research (CIBSR), Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California
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  • Christine Hinard,

    1. Service of Medical Genetics, Geneva University Hospitals, Geneva, Switzerland
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  • Joachim F. Hallmayer,

    1. Center for Interdisciplinary Brain Sciences Research (CIBSR), Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California
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  • John Van Dover Stoecker,

    1. Center for Interdisciplinary Brain Sciences Research (CIBSR), Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California
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  • Stylianos E. Antonarakis,

    1. Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland
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  • Michael A. Morris,

    1. Service of Medical Genetics, Geneva University Hospitals, Geneva, Switzerland
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  • Allan L. Reiss

    1. Center for Interdisciplinary Brain Sciences Research (CIBSR), Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California
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Abstract

22q11.2 deletion syndrome (22q11.2DS) is a well-known genetic risk factor for schizophrenia. The catechol-O-methyltransferase (COMT) gene falls within the 22q11.2 minimal critical region of the deletion. Brain activity, as measured by functional magnetic resonance imaging (fMRI) during a Go/NoGo, response inhibition task was assessed in adolescents with 22q11.2DS (n = 13), typically developing (TD) controls (n = 14), and controls with developmental disability (DD, n = 9). Subjects with 22q11.2DS were also genotyped for the COMT Met/Val polymorphism. Groups did not differ on task performance. However, compared to both control groups, the 22q11.2DS group showed greater brain activation within left parietal regions. Comparison of brain activation between 22q11.2DS Met and Val subgroups revealed significantly increased activation (Met>Val) in the cingulate but not the dorsolateral prefrontal cortex. These preliminary findings suggest that adolescents with 22q11.2DS compensate for executive dysfunction via recruitment of parietal regions. Further, the COMT Met subgroup of 22q11.2DS may recruit additional cingulate activation for tasks requiring attention and inhibition. 22q11.2DS is a unique model for learning about the deleterious effects of decreased dosage of the COMT gene on brain function. Hum Brain Mapp, 2007. © 2007 Wiley-Liss, Inc.

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