Abnormal white matter microstructure and increased extracellular free-water in the cingulum bundle associated with delusions in chronic schizophrenia

Lena K L Oestreich*, Ofer Pasternak, Martha E. Shenton, Marek Kubicki, Xue Gong, Simon McCarthy-Jones, Thomas J. Whitford, Australian Schizophrenia Research Bank

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    21 Citations (Scopus)
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    Abstract

    Background There is growing evidence to suggest that delusions associated with schizophrenia arise from altered structural brain connectivity. The present study investigated whether structural changes in three major fasciculi that interconnect the limbic system – the cingulum bundle, uncinate fasciculus and fornix – are associated with delusions in chronic schizophrenia patients. Methods Free-water corrected Diffusion Tensor Imaging was used to investigate the association between delusions and both microstructural changes within these three fasciculi and extracellular changes in the surrounding free-water. Clinical data and diffusion MRI scans were obtained from 28 healthy controls and 86 schizophrenia patients, of whom 34 had present state delusions, 35 had a lifetime history but currently remitted delusions, and 17 had never experienced delusions. Results While present state and remitted delusions were found to be associated with reduced free-water corrected fractional anisotropy (FAT) and increased free-water corrected radial diffusivity (RDT) in the cingulum bundle bilaterally, extracellular free-water (FW) in the left cingulum bundle was found to be specifically associated with present state delusions in chronic schizophrenia. No changes were observed in the remaining tracts. Conclusions These findings suggest that state and trait delusions in chronic schizophrenia are associated with microstructural processes, such as myelin abnormalities (as indicated by decreased FAT and increased RDT) in the cingulum bundle and that state delusions are additionally associated with extracellular processes such as neuroinflammation or atrophy (as indicated by increased FW) in the left cingulum bundle.

    Original languageEnglish
    Pages (from-to)405-414
    Number of pages10
    JournalNeuroImage: Clinical
    Volume12
    DOIs
    Publication statusPublished - 2016

    Bibliographical note

    Copyright the Author(s) 2016. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

    Keywords

    • Delusions
    • Diffusion Tensor Imaging
    • Free-water imaging
    • Limbic system
    • Schizophrenia

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