title: Characterizing white matter changes in chronic schizophrenia: A free-water imaging multi-site study.
abstract: Diffusion tensor imaging (DTI) studies in chronic schizophrenia have found widespread but often inconsistent patterns of white matter abnormalities. These studies have typically used the conventional measure of fractional anisotropy, which can be contaminated by extracellular free-water. A recent free-water imaging study reported reduced free-water corrected fractional anisotropy (FAT) in chronic schizophrenia across several brain regions, but limited changes in the extracellular volume. The present study set out to validate these findings in a substantially larger sample. Tract-based spatial statistics (TBSS) was performed in 188 healthy controls and 281 chronic schizophrenia patients. Forty-two regions of interest (ROIs), as well as average whole-brain FATand FW were extracted from free-water corrected diffusion tensor maps. Compared to healthy controls, reduced FATwas found in the chronic schizophrenia group in the anterior limb of the internal capsule bilaterally, the posterior thalamic radiation bilaterally, as well as the genu and body of the corpus callosum. While a significant main effect of group was observed for FW, none of the follow-up contrasts survived correction for multiple comparisons. The observed FATreductions in the absence of extracellular FW changes, in a large, multi-site sample of chronic schizophrenia patients, validate the pattern of findings reported by a previous, smaller free-water imaging study of a similar sample. The limited number of regions in which FATwas reduced in the schizophrenia group suggests that actual white matter tissue degeneration in chronic schizophrenia, independent of extracellular FW, might be more localized than suggested previously.
authors.affiliation: Queensland Brain Institute, Centre for Advanced Imaging, The University of Queensland, Brisbane, QLD, Australia. Electronic address: l.oestreich@uq.edu.au.
authors.forename: Lena K L
authors.initials: LKL
authors.lastname: Oestreich
authors.affiliation: Department of Psychiatry, Psychiatry Neuroimaging Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Amanda E
authors.initials: AE
authors.lastname: Lyall
authors.affiliation: Department of Psychiatry, Psychiatry Neuroimaging Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Ofer
authors.initials: O
authors.lastname: Pasternak
authors.affiliation: Department of Psychiatry, Psychiatry Neuroimaging Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Zora
authors.initials: Z
authors.lastname: Kikinis
authors.affiliation: Department of Psychiatry, Psychiatry Neuroimaging Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Dominick T
authors.initials: DT
authors.lastname: Newell
authors.affiliation: Department of Psychiatry, Psychiatry Neuroimaging Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Savadjiev
authors.affiliation: Department of Psychiatry, Psychiatry Neuroimaging Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Bouix
authors.affiliation: Department of Psychiatry, Psychiatry Neuroimaging Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; VA Boston Healthcare System, Boston, MA, USA.
authors.forename: Martha E
authors.initials: ME
authors.lastname: Shenton
authors.affiliation: Department of Psychiatry, Psychiatry Neuroimaging Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Marek
authors.initials: M
authors.lastname: Kubicki
authors.affiliation: Schizophrenia Research Institute, NSW, Australia.
authors.affiliation: School of Psychology, University of New South Wales, NSW, Australia.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Whitford
authors.affiliation: Department of Cognitive Science, Macquarie University, NSW, Australia; Department of Psychiatry, Trinity College Dublin, Ireland.
authors.forename: Simon
authors.initials: S
authors.lastname: McCarthy-Jones
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D016880:Anisotropy; D001315:Australia; D002908:Chronic Disease; D038524:Diffusion Magnetic Resonance Imaging; D005260:Female; D007839:Functional Laterality; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D008875:Middle Aged; D009413:Nerve Fibers, Myelinated / Q000473:pathology; D012559:Schizophrenia / Q000000981:diagnostic imaging* / Q000473:pathology; D014867:Water / Q000378:metabolism*; D066127:White Matter / Q000000981:diagnostic imaging*; D055815:Young Adult
chemical_list: D014867:Water
keywords: Diffusion MRI; ENIGMA; Free-water; Neurodegeneration; Tract-based spatial statistics (TBSS)