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Brain Development in School-Age and Adolescent Girls: Effects of Turner Syndrome, Estrogen Therapy, and Genomic Imprinting

  • Stefani O’Donoghue
    Affiliations
    Center for Interdisciplinary Brain Sciences Research, Stanford University School of Medicine, Stanford, California

    Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California
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  • Tamar Green
    Affiliations
    Center for Interdisciplinary Brain Sciences Research, Stanford University School of Medicine, Stanford, California

    Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California
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  • Judith L. Ross
    Affiliations
    Department of Pediatrics, Thomas Jefferson University, Philadelphia, Pennsylvania
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  • Joachim Hallmayer
    Affiliations
    Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California
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  • Xiaoyan Lin
    Affiliations
    Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California
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  • Booil Jo
    Affiliations
    Center for Interdisciplinary Brain Sciences Research, Stanford University School of Medicine, Stanford, California

    Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California
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  • Lynne C. Huffman
    Affiliations
    Department of Pediatrics, Stanford University School of Medicine, Stanford, California
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  • David S. Hong
    Affiliations
    Center for Interdisciplinary Brain Sciences Research, Stanford University School of Medicine, Stanford, California

    Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California
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  • Allan L. Reiss
    Correspondence
    Address correspondence to Allan L. Reiss, M.D., Robbins Professor of Psychiatry, Radiology and Pediatrics, Stanford University School of Medicine, 401 Quarry Road, Stanford, CA 94305.
    Affiliations
    Center for Interdisciplinary Brain Sciences Research, Stanford University School of Medicine, Stanford, California

    Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California

    Department of Pediatrics, Stanford University School of Medicine, Stanford, California

    Department of Radiology, Stanford University School of Medicine, Stanford, California
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      Abstract

      Background

      The study of Turner syndrome (TS) offers a unique window of opportunity for advancing scientific knowledge of how X chromosome gene imprinting, epigenetic factors, hormonal milieu, and chronologic age affect brain development in females.

      Methods

      We described brain growth trajectories in 55 girls with TS and 53 typically developing girls (258 magnetic resonance imaging datasets) spanning 5 years. Using novel nonparametric and mixed effects analytic approaches, we evaluated influences of X chromosome genomic imprinting and hormone replacement therapy on brain development.

      Results

      Parieto-occipital gray and white matter regions showed slower growth during typical pubertal timing in girls with TS relative to typically developing girls. In contrast, some basal ganglia, cerebellar, and limited cortical areas showed enhanced volume growth with peaks around 10 years of age.

      Conclusions

      The parieto-occipital finding suggests that girls with TS may be particularly vulnerable to altered brain development during adolescence. Basal ganglia regions may be relatively preserved in TS owing to their maturational growth before or early in typical pubertal years. Taken together, our findings indicate that particular brain regions are more vulnerable to TS genetic and hormonal effects during puberty. These specific alterations in neurodevelopment may be more likely to affect long-term cognitive behavioral outcomes in young girls with this common genetic condition.

      Keywords

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