Internal capsule, corpus callosum and long associative fibers in good and poor outcome schizophrenia: A diffusion tensor imaging survey

BACKGROUND Prior voxelwise studies of white matter anisotropy found widespread reductions involving all major fiber tracts of the schizophrenic brain. We set out to confirm these exploratory findings and evaluate their relation to illness severity using a hypothesis-driven region-of-interest approach. METHODS 104 schizophrenia patients (51 with good outcomes, 53 with poor outcomes) and 41 matched comparison subjects participated in the study. Regions of interest were selected on the basis of published voxelwise findings and placed within major fiber tracts using Talairach's stereotaxic coordinates. RESULTS Fractional anisotropy reductions in schizophrenia patients were confirmed in the left cingulum, anterior thalamic radiation, fronto-occipital and inferior longitudinal fasciculi, as well as bilaterally in the corpus callosum, anterior and posterior limbs of internal capsule, superior longitudinal fasciculus, optic radiation, and frontotemporal extrafascicular white matter. Anisotropy reductions were more extensive in patients with poor outcomes ("Kraepelinian"), particularly in the posterior corpus callosum, fronto-occipital fasciculus, left optic radiation and frontotemporal white matter. Lower anisotropy in the right hemisphere tracts was associated with more prominent positive symptomatology, whereas negative symptoms were inversely associated with anisotropy values in both hemispheres. CONCLUSIONS These results support a global neural disconnectivity in schizophrenia patients, which is more severe in those with poor clinical outcomes.

[1]  Dai Zhang,et al.  A diffusion tensor imaging study of middle and superior cerebellar peduncle in male patients with schizophrenia , 2003, Neuroscience Letters.

[2]  S. Scarone,et al.  Anatomical characteristics of the corpus callosum and clinical correlates in schizophrenia , 1993, Schizophrenia Research.

[3]  T. Kinoshita,et al.  Subtle Disruption of the Middle Cerebellar Peduncles in Patients with Schizophrenia , 2004, Neuropsychobiology.

[4]  Adam M. Brickman,et al.  Cortical intercorrelations of frontal area volumes in schizophrenia , 2005, NeuroImage.

[5]  Monte S. Buchsbaum,et al.  Correlations between volumes of the pulvinar, centromedian, and mediodorsal nuclei and cortical Brodmann's areas in schizophrenia , 2006, Neuroscience Letters.

[6]  M. Torrens Co-Planar Stereotaxic Atlas of the Human Brain—3-Dimensional Proportional System: An Approach to Cerebral Imaging, J. Talairach, P. Tournoux. Georg Thieme Verlag, New York (1988), 122 pp., 130 figs. DM 268 , 1990 .

[7]  Yasuhiro Kawasaki,et al.  Decreased volume and increased asymmetry of the anterior limb of the internal capsule in patients with schizophrenia , 2003, Biological Psychiatry.

[8]  S. Wakana,et al.  MRI Atlas of Human White Matter , 2005 .

[9]  Fred L Bookstein,et al.  Landmark-based morphometric analysis of first-episode schizophrenia , 1999, Biological Psychiatry.

[10]  J. Sweeney,et al.  Abnormalities of the corpus callosum in first episode, treatment naive schizophrenia , 2002, Journal of neurology, neurosurgery, and psychiatry.

[11]  Manzar Ashtari,et al.  White matter abnormalities in early-onset schizophrenia: a voxel-based diffusion tensor imaging study. , 2005, Journal of the American Academy of Child and Adolescent Psychiatry.

[12]  Carl-Fredrik Westin,et al.  Fornix Integrity and Hippocampal Volume in Male Schizophrenic Patients , 2006, Biological Psychiatry.

[13]  Lina Shihabuddin,et al.  MRI assessment of gray and white matter distribution in Brodmann's areas of the cortex in patients with schizophrenia with good and poor outcomes. , 2003, The American journal of psychiatry.

[14]  W. Honer,et al.  Reduced anterior internal capsule and thalamic volumes in first-episode psychosis , 2006, Schizophrenia Research.

[15]  Reinhard Steinberg,et al.  Brain dysfunction during motor activation and corpus callosum alterations in Schizophrenia measured by cerebral blood flow and magnetic resonance imaging , 1991, Biological Psychiatry.

[16]  William Byne,et al.  Magnetic resonance imaging of mediodorsal, pulvinar, and centromedian nuclei of the thalamus in patients with schizophrenia. , 2003, Archives of general psychiatry.

[17]  Yasuhiro Kawasaki,et al.  Regional changes in brain gray and white matter in patients with schizophrenia demonstrated with voxel-based analysis of MRI , 2002, Schizophrenia Research.

[18]  Carl-Fredrik Westin,et al.  DTI and MTR abnormalities in schizophrenia: Analysis of white matter integrity , 2005, NeuroImage.

[19]  Jens Frahm,et al.  Topography of the human corpus callosum revisited—Comprehensive fiber tractography using diffusion tensor magnetic resonance imaging , 2006, NeuroImage.

[20]  Cheuk Y. Tang,et al.  Abnormal glucose metabolism in the mediodorsal nucleus of the thalamus in schizophrenia. , 2004, The American journal of psychiatry.

[21]  Derek K. Jones,et al.  Virtual in Vivo Interactive Dissection of White Matter Fasciculi in the Human Brain , 2002, NeuroImage.

[22]  A. Toga,et al.  Mapping morphology of the corpus callosum in schizophrenia. , 2000, Cerebral cortex.

[23]  S. Skare,et al.  Abnormal brain white matter in schizophrenia: a diffusion tensor imaging study , 2001, Neuroreport.

[24]  E. Ludwig,et al.  Atlas cerebri humani , 1956 .

[25]  J. Breeze,et al.  Abnormal anterior cingulum in patients with schizophrenia: a diffusion tensor imaging study , 2003, Neuroreport.

[26]  Talma Hendler,et al.  Regional axonal abnormalities in first episode schizophrenia: Preliminary evidence based on high b-value diffusion-weighted imaging , 2006, Psychiatry Research: Neuroimaging.

[27]  Vaibhav A. Diwadkar,et al.  Abnormalities in MRI-measured signal intensity in the corpus callosum in schizophrenia , 2004, Schizophrenia Research.

[28]  R. Bronen,et al.  MR imaging of the temporal stem: anatomic dissection tractography of the uncinate fasciculus, inferior occipitofrontal fasciculus, and Meyer's loop of the optic radiation. , 2004, AJNR. American journal of neuroradiology.

[29]  K. Davis,et al.  Characteristics of very poor outcome schizophrenia. , 1987, The American journal of psychiatry.

[30]  Carl-Fredrik Westin,et al.  White matter hemisphere asymmetries in healthy subjects and in schizophrenia: a diffusion tensor MRI study , 2004, NeuroImage.

[31]  Stephan Arndt,et al.  Corpus callosum shape and size in male patients with schizophrenia , 1998, Biological Psychiatry.

[32]  Manzar Ashtari,et al.  White matter abnormalities in first-episode schizophrenia or schizoaffective disorder: a diffusion tensor imaging study. , 2005, The American journal of psychiatry.

[33]  Adam M. Brickman,et al.  Cortical intercorrelations of temporal area volumes in schizophrenia , 2005, Schizophrenia Research.

[34]  R. Kikinis,et al.  Uncinate fasciculus findings in schizophrenia: a magnetic resonance diffusion tensor imaging study. , 2002, The American journal of psychiatry.

[35]  Jacqueline Spiegel-Cohen,et al.  Shape and size of the corpus callosum in schizophrenia and schizotypal personality disorder , 2000, Schizophrenia Research.

[36]  Derek K. Jones,et al.  Occipito-temporal connections in the human brain. , 2003, Brain : a journal of neurology.

[37]  Tianzi Jiang,et al.  White matter integrity of the whole brain is disrupted in first-episode schizophrenia , 2006, Neuroreport.

[38]  Hisanobu Kaiya,et al.  The morphology of the corpus callosum in schizophrenia An MRI study , 1988, Schizophrenia Research.

[39]  Zhiguo Sun,et al.  Anterior cingulum abnormalities in male patients with schizophrenia determined through diffusion tensor imaging. , 2004, The American journal of psychiatry.

[40]  I. C. Wright,et al.  Corpus callosum size and inter-hemispheric function in schizophrenia , 1997, Schizophrenia Research.

[41]  Jay N. Giedd,et al.  Corpus callosum development in childhood-onset schizophrenia , 2003, Schizophrenia Research.

[42]  J Schröder,et al.  Corpus callosum in first-episode patients with schizophrenia – a magnetic resonance imaging study , 2003, Psychological Medicine.

[43]  D. Louis Collins,et al.  Focal white matter density changes in schizophrenia: reduced inter-hemispheric connectivity , 2004, NeuroImage.

[44]  J B Poline,et al.  Cerebral gray and white matter reductions and clinical correlates in patients with early onset schizophrenia , 2001, Schizophrenia Research.

[45]  Manzar Ashtari,et al.  Reduced frontal white matter integrity in Early-Onset schizophrenia: a preliminary study , 2004, Biological Psychiatry.

[46]  S. Wakana,et al.  Fiber tract-based atlas of human white matter anatomy. , 2004, Radiology.

[47]  G Price,et al.  The corpus callosum in first episode schizophrenia: a diffusion tensor imaging study , 2005, Journal of Neurology, Neurosurgery & Psychiatry.

[48]  G M Innocenti,et al.  Schizophrenia, neurodevelopment and corpus callosum , 2003, Molecular Psychiatry.

[49]  R. Kikinis,et al.  Cingulate fasciculus integrity disruption in schizophrenia: a magnetic resonance diffusion tensor imaging study , 2003, Biological Psychiatry.

[50]  T. Sigmundsson,et al.  Structural abnormalities in frontal, temporal, and limbic regions and interconnecting white matter tracts in schizophrenic patients with prominent negative symptoms. , 2001, The American journal of psychiatry.

[51]  Lina Shihabuddin,et al.  Internal capsule size in good-outcome and poor-outcome schizophrenia. , 2006, The Journal of neuropsychiatry and clinical neurosciences.

[52]  S. Lawrie,et al.  Structural disconnectivity in schizophrenia: a diffusion tensor magnetic resonance imaging study , 2003, British Journal of Psychiatry.

[53]  Thomas Dierks,et al.  Alterations of white matter connectivity in first episode schizophrenia , 2006, Neurobiology of Disease.

[54]  A. Schleicher,et al.  Mapping of Histologically Identified Long Fiber Tracts in Human Cerebral Hemispheres to the MRI Volume of a Reference Brain: Position and Spatial Variability of the Optic Radiation , 1999, NeuroImage.

[55]  T. Kinoshita,et al.  Diffusion tensor imaging study of the middle cerebellar peduncles in patients with schizophrenia , 2008, The Cerebellum.

[56]  Sukhwinder S. Shergill,et al.  Tract-specific anisotropy measurements in diffusion tensor imaging , 2006, Psychiatry Research: Neuroimaging.

[57]  Cheuk Y. Tang,et al.  Diffusion tensor imaging of frontal lobe white matter tracts in schizophrenia , 2006, Annals of general psychiatry.

[58]  D. Javitt,et al.  Early-stage visual processing and cortical amplification deficits in schizophrenia. , 2005, Archives of general psychiatry.

[59]  H. Axer,et al.  Mapping of fiber orientation in human internal capsule by means of polarized light and confocal scanning laser microscopy , 2000, Journal of Neuroscience Methods.

[60]  D. Javitt,et al.  MRI study of white matter diffusion anisotropy in schizophrenia , 2003, Neuroreport.

[61]  Adam M. Brickman,et al.  Thalamus size and outcome in schizophrenia , 2004, Schizophrenia Research.

[62]  Р Д Синельников Атлас анатомии человека , 1967 .

[63]  J. Foong,et al.  Neuropathological abnormalities of the corpus callosum in schizophrenia: a diffusion tensor imaging study , 2000, Journal of neurology, neurosurgery, and psychiatry.

[64]  M S Buchsbaum,et al.  MRI white matter diffusion anisotropy and PET metabolic rate in schizophrenia , 1998, Neuroreport.

[65]  P W Woodruff,et al.  Meta-analysis of corpus callosum size in schizophrenia. , 1995, Journal of neurology, neurosurgery, and psychiatry.

[66]  Michele Tansella,et al.  Investigation of corpus callosum in schizophrenia with diffusion imaging , 2005, Schizophrenia Research.

[67]  Cheuk Y. Tang,et al.  Diffusion Tensor Imaging in Schizophrenia , 2006, Biological Psychiatry.

[68]  Monte S. Buchsbaum,et al.  White matter fractional anisotropy and outcome in schizophrenia , 2006, Schizophrenia Research.

[69]  G J Barker,et al.  Neuropathological abnormalities in schizophrenia: evidence from magnetization transfer imaging. , 2001, Brain : a journal of neurology.

[70]  P. Golland,et al.  Shape differences in the corpus callosum in first-episode schizophrenia and first-episode psychotic affective disorder. , 2002, The American journal of psychiatry.

[71]  Ferenc Kiss,et al.  Atlas anatomiae corporis humani. , 1975 .

[72]  Richard S. J. Frackowiak,et al.  Cortical and subcortical gray matter abnormalities in schizophrenia determined through structural magnetic resonance imaging with optimized volumetric voxel-based morphometry. , 2002, The American journal of psychiatry.

[73]  Alex L. MacKay,et al.  Smaller corpus callosum subregions containing motor fibers in schizophrenia , 2005, Schizophrenia Research.

[74]  A. D. de Crespigny,et al.  Compromised white matter tract integrity in schizophrenia inferred from diffusion tensor imaging. , 1999, Archives of general psychiatry.

[75]  Adam M. Brickman,et al.  Correlations between MRI-assessed volumes of the thalamus and cortical Brodmann's areas in schizophrenia , 2005, Schizophrenia Research.

[76]  F. Netter Atlas of Human Anatomy , 1967 .

[77]  R. McCarley,et al.  A review of MRI findings in schizophrenia , 2001, Schizophrenia Research.

[78]  W. Honer,et al.  Abnormalities of myelination in schizophrenia detected in vivo with MRI, and post-mortem with analysis of oligodendrocyte proteins , 2003, Molecular Psychiatry.

[79]  D. Hubl,et al.  Pathways that make voices: white matter changes in auditory hallucinations. , 2004, Archives of general psychiatry.

[80]  M. Mulligan,et al.  International anatomical terminology , 2006, Skeletal Radiology.

[81]  John J. Foxe,et al.  Visual white matter integrity in schizophrenia. , 2006, The American journal of psychiatry.

[82]  Katrin Amunts,et al.  White matter fiber tracts of the human brain: Three-dimensional mapping at microscopic resolution, topography and intersubject variability , 2006, NeuroImage.

[83]  Paul J. Harrison,et al.  Asymmetry of the uncinate fasciculus: a post-mortem study of normal subjects and patients with schizophrenia. , 2002, Cerebral cortex.

[84]  Frans Vos,et al.  Shaving diffusion tensor images in discriminant analysis: A study into schizophrenia , 2006, Medical Image Anal..

[85]  Toshihiko Kinoshita,et al.  Neural disorganization in the superior cerebellar peduncle and cognitive abnormality in patients with schizophrenia: A diffusion tensor imaging study , 2006, Progress in Neuro-Psychopharmacology and Biological Psychiatry.