Callosal Thickness Reductions Relate to Facial Dysmorphology in Fetal Alcohol Spectrum Disorders

Authors

  • Yaling Yang,

    1. From the Laboratory of Neuro Imaging, Department of Neurology (YY, ORP, KLN), University of California, Los Angeles; Developmental Cognitive Neuroimaging Laboratory, Department of Pediatrics (EK, ERS), Keck School of Medicine, University of Southern California; Division of Research on Children, Youth, and Families, Department of Pediatrics (EK, ERS), Children’s Hospital Los Angeles, Los Angeles, California; Bowles Center for Alcohol Studies (KKS), University of North Carolina, Chapel Hill, North Carolina; Department of Psychology (SNM, EPR) Center for Behavioral Teratology, San Diego State University, San Diego, California; Department of Pediatrics, Division of Dysmorphology/Teratology (KLJ), University of California, San Diego, La Jolla, California; Department of Psychiatry and Mental Health (CMA), University of Cape Town, Cape Town, South Africa; Departments of Sociology and Family and Community Medicine and the Center on Alcoholism, Substance Abuse and Addictions (PAM), The University of New Mexico, Albuquerque, New Mexico; Department of Psychiatry and Biobehavioral Sciences (MJO), David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.
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  • Owen R. Phillips,

    1. From the Laboratory of Neuro Imaging, Department of Neurology (YY, ORP, KLN), University of California, Los Angeles; Developmental Cognitive Neuroimaging Laboratory, Department of Pediatrics (EK, ERS), Keck School of Medicine, University of Southern California; Division of Research on Children, Youth, and Families, Department of Pediatrics (EK, ERS), Children’s Hospital Los Angeles, Los Angeles, California; Bowles Center for Alcohol Studies (KKS), University of North Carolina, Chapel Hill, North Carolina; Department of Psychology (SNM, EPR) Center for Behavioral Teratology, San Diego State University, San Diego, California; Department of Pediatrics, Division of Dysmorphology/Teratology (KLJ), University of California, San Diego, La Jolla, California; Department of Psychiatry and Mental Health (CMA), University of Cape Town, Cape Town, South Africa; Departments of Sociology and Family and Community Medicine and the Center on Alcoholism, Substance Abuse and Addictions (PAM), The University of New Mexico, Albuquerque, New Mexico; Department of Psychiatry and Biobehavioral Sciences (MJO), David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.
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  • Eric Kan,

    1. From the Laboratory of Neuro Imaging, Department of Neurology (YY, ORP, KLN), University of California, Los Angeles; Developmental Cognitive Neuroimaging Laboratory, Department of Pediatrics (EK, ERS), Keck School of Medicine, University of Southern California; Division of Research on Children, Youth, and Families, Department of Pediatrics (EK, ERS), Children’s Hospital Los Angeles, Los Angeles, California; Bowles Center for Alcohol Studies (KKS), University of North Carolina, Chapel Hill, North Carolina; Department of Psychology (SNM, EPR) Center for Behavioral Teratology, San Diego State University, San Diego, California; Department of Pediatrics, Division of Dysmorphology/Teratology (KLJ), University of California, San Diego, La Jolla, California; Department of Psychiatry and Mental Health (CMA), University of Cape Town, Cape Town, South Africa; Departments of Sociology and Family and Community Medicine and the Center on Alcoholism, Substance Abuse and Addictions (PAM), The University of New Mexico, Albuquerque, New Mexico; Department of Psychiatry and Biobehavioral Sciences (MJO), David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.
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  • Kathleen K. Sulik,

    1. From the Laboratory of Neuro Imaging, Department of Neurology (YY, ORP, KLN), University of California, Los Angeles; Developmental Cognitive Neuroimaging Laboratory, Department of Pediatrics (EK, ERS), Keck School of Medicine, University of Southern California; Division of Research on Children, Youth, and Families, Department of Pediatrics (EK, ERS), Children’s Hospital Los Angeles, Los Angeles, California; Bowles Center for Alcohol Studies (KKS), University of North Carolina, Chapel Hill, North Carolina; Department of Psychology (SNM, EPR) Center for Behavioral Teratology, San Diego State University, San Diego, California; Department of Pediatrics, Division of Dysmorphology/Teratology (KLJ), University of California, San Diego, La Jolla, California; Department of Psychiatry and Mental Health (CMA), University of Cape Town, Cape Town, South Africa; Departments of Sociology and Family and Community Medicine and the Center on Alcoholism, Substance Abuse and Addictions (PAM), The University of New Mexico, Albuquerque, New Mexico; Department of Psychiatry and Biobehavioral Sciences (MJO), David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.
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  • Sarah N. Mattson,

    1. From the Laboratory of Neuro Imaging, Department of Neurology (YY, ORP, KLN), University of California, Los Angeles; Developmental Cognitive Neuroimaging Laboratory, Department of Pediatrics (EK, ERS), Keck School of Medicine, University of Southern California; Division of Research on Children, Youth, and Families, Department of Pediatrics (EK, ERS), Children’s Hospital Los Angeles, Los Angeles, California; Bowles Center for Alcohol Studies (KKS), University of North Carolina, Chapel Hill, North Carolina; Department of Psychology (SNM, EPR) Center for Behavioral Teratology, San Diego State University, San Diego, California; Department of Pediatrics, Division of Dysmorphology/Teratology (KLJ), University of California, San Diego, La Jolla, California; Department of Psychiatry and Mental Health (CMA), University of Cape Town, Cape Town, South Africa; Departments of Sociology and Family and Community Medicine and the Center on Alcoholism, Substance Abuse and Addictions (PAM), The University of New Mexico, Albuquerque, New Mexico; Department of Psychiatry and Biobehavioral Sciences (MJO), David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.
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  • Edward P. Riley,

    1. From the Laboratory of Neuro Imaging, Department of Neurology (YY, ORP, KLN), University of California, Los Angeles; Developmental Cognitive Neuroimaging Laboratory, Department of Pediatrics (EK, ERS), Keck School of Medicine, University of Southern California; Division of Research on Children, Youth, and Families, Department of Pediatrics (EK, ERS), Children’s Hospital Los Angeles, Los Angeles, California; Bowles Center for Alcohol Studies (KKS), University of North Carolina, Chapel Hill, North Carolina; Department of Psychology (SNM, EPR) Center for Behavioral Teratology, San Diego State University, San Diego, California; Department of Pediatrics, Division of Dysmorphology/Teratology (KLJ), University of California, San Diego, La Jolla, California; Department of Psychiatry and Mental Health (CMA), University of Cape Town, Cape Town, South Africa; Departments of Sociology and Family and Community Medicine and the Center on Alcoholism, Substance Abuse and Addictions (PAM), The University of New Mexico, Albuquerque, New Mexico; Department of Psychiatry and Biobehavioral Sciences (MJO), David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.
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  • Kenneth L. Jones,

    1. From the Laboratory of Neuro Imaging, Department of Neurology (YY, ORP, KLN), University of California, Los Angeles; Developmental Cognitive Neuroimaging Laboratory, Department of Pediatrics (EK, ERS), Keck School of Medicine, University of Southern California; Division of Research on Children, Youth, and Families, Department of Pediatrics (EK, ERS), Children’s Hospital Los Angeles, Los Angeles, California; Bowles Center for Alcohol Studies (KKS), University of North Carolina, Chapel Hill, North Carolina; Department of Psychology (SNM, EPR) Center for Behavioral Teratology, San Diego State University, San Diego, California; Department of Pediatrics, Division of Dysmorphology/Teratology (KLJ), University of California, San Diego, La Jolla, California; Department of Psychiatry and Mental Health (CMA), University of Cape Town, Cape Town, South Africa; Departments of Sociology and Family and Community Medicine and the Center on Alcoholism, Substance Abuse and Addictions (PAM), The University of New Mexico, Albuquerque, New Mexico; Department of Psychiatry and Biobehavioral Sciences (MJO), David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.
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  • Colleen M. Adnams,

    1. From the Laboratory of Neuro Imaging, Department of Neurology (YY, ORP, KLN), University of California, Los Angeles; Developmental Cognitive Neuroimaging Laboratory, Department of Pediatrics (EK, ERS), Keck School of Medicine, University of Southern California; Division of Research on Children, Youth, and Families, Department of Pediatrics (EK, ERS), Children’s Hospital Los Angeles, Los Angeles, California; Bowles Center for Alcohol Studies (KKS), University of North Carolina, Chapel Hill, North Carolina; Department of Psychology (SNM, EPR) Center for Behavioral Teratology, San Diego State University, San Diego, California; Department of Pediatrics, Division of Dysmorphology/Teratology (KLJ), University of California, San Diego, La Jolla, California; Department of Psychiatry and Mental Health (CMA), University of Cape Town, Cape Town, South Africa; Departments of Sociology and Family and Community Medicine and the Center on Alcoholism, Substance Abuse and Addictions (PAM), The University of New Mexico, Albuquerque, New Mexico; Department of Psychiatry and Biobehavioral Sciences (MJO), David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.
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  • Philip A. May,

    1. From the Laboratory of Neuro Imaging, Department of Neurology (YY, ORP, KLN), University of California, Los Angeles; Developmental Cognitive Neuroimaging Laboratory, Department of Pediatrics (EK, ERS), Keck School of Medicine, University of Southern California; Division of Research on Children, Youth, and Families, Department of Pediatrics (EK, ERS), Children’s Hospital Los Angeles, Los Angeles, California; Bowles Center for Alcohol Studies (KKS), University of North Carolina, Chapel Hill, North Carolina; Department of Psychology (SNM, EPR) Center for Behavioral Teratology, San Diego State University, San Diego, California; Department of Pediatrics, Division of Dysmorphology/Teratology (KLJ), University of California, San Diego, La Jolla, California; Department of Psychiatry and Mental Health (CMA), University of Cape Town, Cape Town, South Africa; Departments of Sociology and Family and Community Medicine and the Center on Alcoholism, Substance Abuse and Addictions (PAM), The University of New Mexico, Albuquerque, New Mexico; Department of Psychiatry and Biobehavioral Sciences (MJO), David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.
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  • Mary J. O’Connor,

    1. From the Laboratory of Neuro Imaging, Department of Neurology (YY, ORP, KLN), University of California, Los Angeles; Developmental Cognitive Neuroimaging Laboratory, Department of Pediatrics (EK, ERS), Keck School of Medicine, University of Southern California; Division of Research on Children, Youth, and Families, Department of Pediatrics (EK, ERS), Children’s Hospital Los Angeles, Los Angeles, California; Bowles Center for Alcohol Studies (KKS), University of North Carolina, Chapel Hill, North Carolina; Department of Psychology (SNM, EPR) Center for Behavioral Teratology, San Diego State University, San Diego, California; Department of Pediatrics, Division of Dysmorphology/Teratology (KLJ), University of California, San Diego, La Jolla, California; Department of Psychiatry and Mental Health (CMA), University of Cape Town, Cape Town, South Africa; Departments of Sociology and Family and Community Medicine and the Center on Alcoholism, Substance Abuse and Addictions (PAM), The University of New Mexico, Albuquerque, New Mexico; Department of Psychiatry and Biobehavioral Sciences (MJO), David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.
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  • Katherine L. Narr,

    1. From the Laboratory of Neuro Imaging, Department of Neurology (YY, ORP, KLN), University of California, Los Angeles; Developmental Cognitive Neuroimaging Laboratory, Department of Pediatrics (EK, ERS), Keck School of Medicine, University of Southern California; Division of Research on Children, Youth, and Families, Department of Pediatrics (EK, ERS), Children’s Hospital Los Angeles, Los Angeles, California; Bowles Center for Alcohol Studies (KKS), University of North Carolina, Chapel Hill, North Carolina; Department of Psychology (SNM, EPR) Center for Behavioral Teratology, San Diego State University, San Diego, California; Department of Pediatrics, Division of Dysmorphology/Teratology (KLJ), University of California, San Diego, La Jolla, California; Department of Psychiatry and Mental Health (CMA), University of Cape Town, Cape Town, South Africa; Departments of Sociology and Family and Community Medicine and the Center on Alcoholism, Substance Abuse and Addictions (PAM), The University of New Mexico, Albuquerque, New Mexico; Department of Psychiatry and Biobehavioral Sciences (MJO), David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.
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  • Elizabeth R. Sowell

    1. From the Laboratory of Neuro Imaging, Department of Neurology (YY, ORP, KLN), University of California, Los Angeles; Developmental Cognitive Neuroimaging Laboratory, Department of Pediatrics (EK, ERS), Keck School of Medicine, University of Southern California; Division of Research on Children, Youth, and Families, Department of Pediatrics (EK, ERS), Children’s Hospital Los Angeles, Los Angeles, California; Bowles Center for Alcohol Studies (KKS), University of North Carolina, Chapel Hill, North Carolina; Department of Psychology (SNM, EPR) Center for Behavioral Teratology, San Diego State University, San Diego, California; Department of Pediatrics, Division of Dysmorphology/Teratology (KLJ), University of California, San Diego, La Jolla, California; Department of Psychiatry and Mental Health (CMA), University of Cape Town, Cape Town, South Africa; Departments of Sociology and Family and Community Medicine and the Center on Alcoholism, Substance Abuse and Addictions (PAM), The University of New Mexico, Albuquerque, New Mexico; Department of Psychiatry and Biobehavioral Sciences (MJO), David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.
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Reprint requests: Elizabeth Sowell, PhD, Developmental Cognitive Neuroimaging Laboratory, Department of Pediatrics, Keck School of Medicine, University of Southern California, 4650 Sunset Blvd., Mailstop #130, Los Angeles, CA 90027; Tel.: 323-361-7347; Fax: 323-361-7836; E-mail: esowell@chla.usc.edu

Abstract

Background:  Structural abnormalities of the corpus callosum (CC), such as reduced size and increased shape variability, have been documented in individuals with fetal alcohol spectrum disorders (FASD). However, the regional specificity of altered CC structure, which may point to the timing of neurodevelopmental disturbances and/or relate to specific functional impairments, remains unclear. Furthermore, associations between facial dysmorphology and callosal structure remain undetermined.

Methods:  One hundred and fifty-three participants (age range 8 to 16) including 82 subjects with FASD and 71 nonexposed controls were included in this study. The structural magnetic resonance imaging data of these subjects was collected at 3 sites (Los Angeles and San Diego, California, and Cape Town, South Africa) and analyzed using classical parcellation schemes, as well as more refined surface-based geometrical modeling methods, to identify callosal morphological alterations in FASD at high spatial resolution.

Results:  Reductions in callosal thickness and area, specifically in the anterior third and the splenium, were observed in FASD compared with nonexposed controls. In addition, reduced CC thickness and area significantly correlated with reduced palpebral fissure length.

Conclusions:  Consistent with previous reports, findings suggest an adverse effect of prenatal alcohol exposure on callosal growth and further indicate that fiber pathways connecting frontal and parieto-occipital regions in each hemisphere may be particularly affected. Significant associations between callosal and facial dysmorphology provide evidence for a concurrent insult to midline facial and brain structural development in FASD.

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