title: Altered interhemispheric and temporal lobe white matter microstructural organization in severe chronic schizophrenia.
abstract: Diffusion MRI investigations in schizophrenia provide evidence of abnormal white matter (WM) microstructural organization as indicated by reduced fractional anisotropy (FA) primarily in interhemispheric, left frontal and temporal WM. Using tract-based spatial statistics (TBSS), we examined diffusion parameters in a sample of patients with severe chronic schizophrenia. Diffusion MRI data were acquired on 19 patients with chronic severe schizophrenia and 19 age- and gender-matched healthy controls using a 64 gradient direction sequence, (b=1300 s/mm(2)) collected on a Siemens 1.5T MRI scanner. Diagnosis of schizophrenia was determined by Diagnostic and Statistical Manual for Mental Disorders 4th Edition (DSM-IV) Structured Clinical Interview for DSM disorder (SCID). Patients were treatment resistance, having failed to respond to at least two antipsychotic medications, and had prolonged periods of moderate to severe positive or negative symptoms. Analysis of diffusion parameters was carried out using TBSS. Individuals with chronic severe schizophrenia had significantly reduced FA with corresponding increased radial diffusivity in the genu, body, and splenium of the corpus callosum, the right posterior limb of the internal capsule, right external capsule, and the right temporal inferior longitudinal fasciculus. There were no voxels of significantly increased FA in patients compared with controls. A decrease in splenium FA was shown to be related to a longer illness duration. We detected widespread abnormal diffusivity properties in the callosal and temporal lobe WM regions in individuals with severe chronic schizophrenia who have not previously been exposed to clozapine. These deficits can be driven by a number of factors that are indistinguishable using in vivo diffusion-weighted imaging, but may be related to reduced axonal number or packing density, abnormal glial cell arrangement or function, and reduced myelin.
authors.affiliation: Clinical Neuroimaging Laboratory, Department of Anatomy, School of Medicine, College of Medicine, Nursing and Health Sciences, Clinical Science Institute, National University of Ireland Galway, Galway, Ireland.
authors.forename: Laurena
authors.initials: L
authors.lastname: Holleran
authors.affiliation: Clinical Neuroimaging Laboratory, Department of Psychiatry, School of Medicine, College of Medicine, Nursing and Health Sciences, National University of Ireland Galway, Galway, Ireland.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Ahmed
authors.affiliation: 1] Clinical Neuroimaging Laboratory, Department of Psychiatry, School of Medicine, College of Medicine, Nursing and Health Sciences, National University of Ireland Galway, Galway, Ireland [2] Department of Psychiatry and Psychotherapy, University Medical Centre Goettingen, Goettingen, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Anderson-Schmidt
authors.affiliation: Clinical Neuroimaging Laboratory, Department of Psychiatry, School of Medicine, College of Medicine, Nursing and Health Sciences, National University of Ireland Galway, Galway, Ireland.
authors.forename: John
authors.initials: J
authors.lastname: McFarland
authors.affiliation: 1] Clinical Neuroimaging Laboratory, Department of Psychiatry, School of Medicine, College of Medicine, Nursing and Health Sciences, National University of Ireland Galway, Galway, Ireland [2] Department of Radiology, University Hospital of KU Leuven, Leuven, Belgium.
authors.forename: Louise
authors.initials: L
authors.lastname: Emsell
authors.affiliation: Image Sciences Institute, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Alexander
authors.initials: A
authors.lastname: Leemans
authors.affiliation: Clinical Neuroimaging Laboratory, Department of Psychiatry, School of Medicine, College of Medicine, Nursing and Health Sciences, National University of Ireland Galway, Galway, Ireland.
authors.forename: Cathy
authors.initials: C
authors.lastname: Scanlon
authors.affiliation: Clinical Neuroimaging Laboratory, Department of Anatomy, School of Medicine, College of Medicine, Nursing and Health Sciences, Clinical Science Institute, National University of Ireland Galway, Galway, Ireland.
authors.forename: Peter
authors.initials: P
authors.lastname: Dockery
authors.affiliation: Clinical Neuroimaging Laboratory, Department of Radiology, School of Medicine, College of Medicine, Nursing and Health Sciences, National University of Ireland Galway, Galway, Ireland.
authors.forename: Peter
authors.initials: P
authors.lastname: McCarthy
authors.affiliation: King's College London, Centre for Neuroimaging Sciences, Department of Neuroimaging, Institute of Psychiatry, London, UK.
authors.forename: Gareth J
authors.identifier: 0000000252147421
authors.initials: GJ
authors.lastname: Barker
authors.affiliation: Clinical Neuroimaging Laboratory, Department of Psychiatry, School of Medicine, College of Medicine, Nursing and Health Sciences, National University of Ireland Galway, Galway, Ireland.
authors.forename: Colm
authors.initials: C
authors.lastname: McDonald
authors.affiliation: Clinical Neuroimaging Laboratory, Department of Anatomy, School of Medicine, College of Medicine, Nursing and Health Sciences, Clinical Science Institute, National University of Ireland Galway, Galway, Ireland.
authors.forename: Dara M
authors.initials: DM
authors.lastname: Cannon
mesh_terms: D000328:Adult; D016880:Anisotropy; D002908:Chronic Disease; D003337:Corpus Callosum / Q000473:pathology*; D038524:Diffusion Magnetic Resonance Imaging; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D008875:Middle Aged; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000473:pathology*; D013702:Temporal Lobe / Q000473:pathology*