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Fiber-specific measures of white matter microstructure and macrostructure are associated with internalizing and externalizing symptoms in children born very preterm and full-term.

  • Courtney P. Gilchrist
    Correspondence
    Corresponding author pre-publication: Courtney P. Gilchrist,
    Affiliations
    School of Health and Biomedical Sciences, RMIT University, Bundoora, Australia

    Victorian Infant Brain Studies, Murdoch Children’s Research Institute, Melbourne, Australia

    Developmental Imaging, Murdoch Children’s Research Institute, Melbourne, Australia
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  • Claire E. Kelly
    Affiliations
    Victorian Infant Brain Studies, Murdoch Children’s Research Institute, Melbourne, Australia

    Developmental Imaging, Murdoch Children’s Research Institute, Melbourne, Australia

    Turner Institute for Brain and Mental Health, School of Psychological Sciences, Monash University, Clayton, Australia
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  • Angela Cumberland
    Affiliations
    School of Health and Biomedical Sciences, RMIT University, Bundoora, Australia
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  • Thijs Dhollander
    Affiliations
    Developmental Imaging, Murdoch Children’s Research Institute, Melbourne, Australia
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  • Karli Treyvaud
    Affiliations
    Victorian Infant Brain Studies, Murdoch Children’s Research Institute, Melbourne, Australia

    Department of Psychology and Counselling, La Trobe University, Melbourne, Australia

    Newborn Research, Royal Women's Hospital, Melbourne, Victoria, Australia
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  • Katherine Lee
    Affiliations
    Victorian Infant Brain Studies, Murdoch Children’s Research Institute, Melbourne, Australia

    Clinical Epidemiology and Biostatistics Unit, Murdoch Children’s Research Institute, Melbourne, Australia

    Department of Paediatrics, University of Melbourne, Melbourne, Australia
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  • Jeanie L.Y. Cheong
    Affiliations
    Victorian Infant Brain Studies, Murdoch Children’s Research Institute, Melbourne, Australia

    Newborn Research, Royal Women's Hospital, Melbourne, Victoria, Australia

    Department of Obstetrics and Gynaecology, University of Melbourne, Parkville, Australia
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  • Lex W. Doyle
    Affiliations
    Victorian Infant Brain Studies, Murdoch Children’s Research Institute, Melbourne, Australia

    Newborn Research, Royal Women's Hospital, Melbourne, Victoria, Australia

    Department of Paediatrics, University of Melbourne, Melbourne, Australia

    Department of Obstetrics and Gynaecology, University of Melbourne, Parkville, Australia
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  • Terrie E. Inder
    Affiliations
    Victorian Infant Brain Studies, Murdoch Children’s Research Institute, Melbourne, Australia

    Brigham and Women’s Hospital, Harvard Medical School, Boston, USA
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  • Deanne K. Thompson
    Affiliations
    Victorian Infant Brain Studies, Murdoch Children’s Research Institute, Melbourne, Australia

    Developmental Imaging, Murdoch Children’s Research Institute, Melbourne, Australia

    Department of Paediatrics, University of Melbourne, Melbourne, Australia
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  • Author Footnotes
    ∗ MT and PJA should be considered joint senior authors
    Mary Tolcos
    Footnotes
    ∗ MT and PJA should be considered joint senior authors
    Affiliations
    School of Health and Biomedical Sciences, RMIT University, Bundoora, Australia
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  • Author Footnotes
    ∗ MT and PJA should be considered joint senior authors
    Peter J. Anderson
    Correspondence
    Corresponding author for post-publication: Peter J. Anderson, Turner Institute for Brain and Mental Health, 18 Innovation Walk, Monash University, Clayton, VIC 3800, Australia, T: +61 3 9905 9889.
    Footnotes
    ∗ MT and PJA should be considered joint senior authors
    Affiliations
    Victorian Infant Brain Studies, Murdoch Children’s Research Institute, Melbourne, Australia

    Turner Institute for Brain and Mental Health, School of Psychological Sciences, Monash University, Clayton, Australia
    Search for articles by this author
  • Author Footnotes
    ∗ MT and PJA should be considered joint senior authors
Published:September 16, 2022DOI:https://doi.org/10.1016/j.biopsych.2022.09.011

      ABSTRACT

      Background

      Tensor-based investigations suggest that delayed or disrupted white matter (WM) development may relate to adverse behavioral outcomes in individuals born very preterm (VP), however, metrics derived from such models lack specificity. Here, we applied a fixel-based analysis framework to examine WM microstructural and macrostructural correlates of concurrent internalizing and externalizing problems in VP and full-term (FT) children at 7 and 13 years.

      Methods

      Diffusion imaging data were collected in a longitudinal cohort of VP and FT individuals (130 VP, 29 FT at 7 years; 125 VP, 44 FT at 13 years). Fixel-based measures of fiber density (FD), fiber-bundle cross-section (FC) and fiber density and cross-section (FDC) were extracted from 21 WM tracts previously implicated in psychopathology. Internalizing and externalizing symptoms were assessed using the Strengths and Difficulties Questionnaire parent report at 7 and 13 years.

      Results

      At age 7 years, widespread reductions in FC and FDC and tract-specific reductions in FD were related to more internalizing and externalizing symptoms irrespective of birth group. At age 13 years, fixel-based measures were not related to internalizing symptoms, while tract-specific reductions in FD, FC, FDC measures were related to more externalizing symptoms in the FT group only.

      Conclusions

      Age-specific neurobiological markers of internalizing and externalizing problems identified in this study extend previous tensor-based findings to inform pathophysiological models of behavior problems and provide the foundation for investigations into novel preventative and therapeutic intervention to mitigate risk in VP and other high-risk infant populations.

      Keywords

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