title: Multimodal white matter imaging to investigate reduced fractional anisotropy and its age-related decline in schizophrenia.
abstract: We hypothesized that reduced fractional anisotropy (FA) of water diffusion and its elevated aging-related decline in schizophrenia patients may be caused by elevated hyperintensive white matter (HWM) lesions, by reduced permeability-diffusivity index (PDI), or both. We tested this hypothesis in 40/30 control/patient participants. FA values for the corpus callosum were calculated from high angular resolution diffusion tensor imaging (DTI). Whole-brain volume of HWM lesions was quantified by 3D-T2w-fluid-attenuated inversion recovery (FLAIR) imaging. PDI for corpus callosum was ascertained using multi b-value diffusion imaging (15 b-shells with 30 directions per shell). Patients had significantly lower corpus callosum FA values, and there was a significant age-by-diagnosis interaction. Patients also had significantly reduced PDI but no difference in HWM volume. PDI and HWM volume were significant predictors of FA and captured the diagnosis-related variance. Separately, PDI robustly explained FA variance in schizophrenia patients, but not in controls. Conversely, HWM volume made equally significant contributions to variability in FA in both groups. The diagnosis-by-age effect of FA was explained by a PDI-by-diagnosis interaction. Post hoc testing showed a similar trend for PDI of gray mater. Our study demonstrated that reduced FA and its accelerated decline with age in schizophrenia were explained by pathophysiology indexed by PDI, rather than HWM volume.
authors.affiliation: Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD 21228, USA; Department of Physics, University of Maryland Baltimore County, Baltimore, MD 21250, USA. Electronic address: pkochunov@mprc.umaryland.edu.
authors.forename: Peter
authors.initials: P
authors.lastname: Kochunov
authors.affiliation: Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD 21228, USA.
authors.forename: Joshua
authors.initials: J
authors.lastname: Chiappelli
authors.affiliation: Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD 21228, USA.
authors.forename: Susan N
authors.initials: SN
authors.lastname: Wright
authors.affiliation: Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD 21228, USA.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Rowland
authors.affiliation: Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD 21228, USA.
authors.forename: Beenish
authors.initials: B
authors.lastname: Patel
authors.affiliation: Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD 21228, USA.
authors.forename: S Andrea
authors.initials: SA
authors.lastname: Wijtenburg
authors.affiliation: Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD 21228, USA.
authors.forename: Katie
authors.initials: K
authors.lastname: Nugent
authors.affiliation: Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD 21228, USA.
authors.forename: Robert P
authors.initials: RP
authors.lastname: McMahon
authors.affiliation: Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD 21228, USA.
authors.forename: William T
authors.initials: WT
authors.lastname: Carpenter
authors.affiliation: Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD 21228, USA.
authors.forename: Florian
authors.initials: F
authors.lastname: Muellerklein
authors.affiliation: Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD 21228, USA.
authors.forename: Hemalatha
authors.initials: H
authors.lastname: Sampath
authors.affiliation: Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD 21228, USA.
authors.forename: L Elliot
authors.initials: LE
authors.lastname: Hong
mesh_terms: D000328:Adult; D000375:Aging / Q000473:pathology*; D016880:Anisotropy; D001369:Axons / Q000378:metabolism*; D001921:Brain / Q000473:pathology; D003337:Corpus Callosum / Q000378:metabolism / Q000473:pathology*; D056324:Diffusion Tensor Imaging; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D008875:Middle Aged; D064847:Multimodal Imaging; D010539:Permeability; D012559:Schizophrenia / Q000378:metabolism / Q000473:pathology*; D066127:White Matter / Q000378:metabolism / Q000473:pathology*
keywords: Advanced DTI; Diffusivity; Hyperintensive white matter lesions; Permeability