Diffusion Tensor Imaging in Schizophrenia

BACKGROUND Diffusion tensor imaging (DTI) is a relatively new neuroimaging technique that can be used to examine the microstructure of white matter in vivo. A systematic review of DTI studies in schizophrenia was undertaken to test the hypothesis that DTI can detect white matter differences between schizophrenia patients and normal control subjects. METHODS EMBASE, PubMed, Medline, and PsychInfo were searched online and key journals were searched manually for studies comparing anisotropy (a measure of white matter integrity) between patients and control subjects. Nineteen articles were systematically reviewed. RESULTS Though 16 studies found differences, methodological and data differences prevented a meta-analysis. Fourteen studies found reduced anisotropy in patients; two studies found only a loss of normal asymmetry. The region of investigation varied across studies, however, and when the same region (for example, the cingulum) was examined in different studies, as many failed to find a difference as found one. These inconsistencies may be the result of small sample sizes and differences in methodology. CONCLUSIONS Diffusion tensor imaging has yet to provide consistent findings of white matter abnormalities in schizophrenia. Its potential as a means of examining anatomical connectivity may be realized with the study of larger, more homogenous groups of subjects and with ongoing improvements in image analysis.

[1]  H. Holcomb,et al.  The limbic cortex in schizophrenia: focus on the anterior cingulate , 2000, Brain Research Reviews.

[2]  Daniel C Javitt,et al.  DTI and impulsivity in schizophrenia: a first voxelwise correlational analysis , 2004, Neuroreport.

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

[4]  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.

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

[6]  K. Lim,et al.  Age‐related decline in brain white matter anisotropy measured with spatially corrected echo‐planar diffusion tensor imaging , 2000, Magnetic resonance in medicine.

[7]  Gareth J. Barker,et al.  Diffusion tractography based group mapping of major white-matter pathways in the human brain , 2003, NeuroImage.

[8]  P. Goldman-Rakic,et al.  Elevated neuronal density in prefrontal area 46 in brains from schizophrenic patients: Application of a three‐dimensional, stereologic counting method , 1998, The Journal of comparative neurology.

[9]  P. Basser,et al.  In vivo fiber tractography using DT‐MRI data , 2000, Magnetic resonance in medicine.

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

[11]  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.

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

[13]  C. Frith,et al.  Disordered functional connectivity in schizophrenia , 1996, Psychological Medicine.

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

[15]  Thomas E. Nichols,et al.  Anterior cingulate gyrus dysfunction and selective attention deficits in schizophrenia: [15O]H2O PET study during single-trial Stroop task performance. , 1997, The American journal of psychiatry.

[16]  C. Beaulieu,et al.  The basis of anisotropic water diffusion in the nervous system – a technical review , 2002, NMR in biomedicine.

[17]  G J Barker,et al.  Diffusion tensor imaging of cryptogenic and acquired partial epilepsies. , 2001, Brain : a journal of neurology.

[18]  A. Simmons,et al.  Corpus callosum area and functioning in schizophrenic patients with auditory–verbal hallucinations , 2001, Schizophrenia Research.

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

[20]  Geoffrey J M Parker,et al.  A framework for a streamline‐based probabilistic index of connectivity (PICo) using a structural interpretation of MRI diffusion measurements , 2003, Journal of magnetic resonance imaging : JMRI.

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

[22]  E. Crosby,et al.  Correlative Anatomy of the Nervous System , 1962 .

[23]  R. Murray,et al.  Meta-analysis of regional brain volumes in schizophrenia. , 2000, The American journal of psychiatry.

[24]  S. Paradiso,et al.  "Cognitive dysmetria" as an integrative theory of schizophrenia: a dysfunction in cortical-subcortical-cerebellar circuitry? , 1998, Schizophrenia bulletin.

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

[26]  E. G. Jones,et al.  Maldistribution of interstitial neurons in prefrontal white matter of the brains of schizophrenic patients. , 1996, Archives of general psychiatry.

[27]  S. Skare,et al.  Noise considerations in the determination of diffusion tensor anisotropy. , 2000, Magnetic resonance imaging.

[28]  T. J. Crow,et al.  Schizophrenia as a transcallosal misconnection syndrome , 1998, Schizophrenia Research.

[29]  O Salonen,et al.  Regional gray matter, white matter, and cerebrospinal fluid distributions in schizophrenic patients, their siblings, and controls. , 1998, Archives of general psychiatry.

[30]  S. Kay,et al.  The positive and negative syndrome scale (PANSS) for schizophrenia. , 1987, Schizophrenia bulletin.

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

[32]  René Westerhausen,et al.  The influence of handedness and gender on the microstructure of the human corpus callosum: a diffusion-tensor magnetic resonance imaging study , 2003, Neuroscience Letters.

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

[34]  Adolf Pfefferbaum,et al.  Microstructural but Not Macrostructural Disruption of White Matter in Women with Chronic Alcoholism , 2002, NeuroImage.

[35]  John Suckling,et al.  Global, voxel, and cluster tests, by theory and permutation, for a difference between two groups of structural MR images of the brain , 1999, IEEE Transactions on Medical Imaging.

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

[37]  R. Poldrack,et al.  Microstructure of Temporo-Parietal White Matter as a Basis for Reading Ability Evidence from Diffusion Tensor Magnetic Resonance Imaging , 2000, Neuron.

[38]  G. Pearlson,et al.  Structural evaluation of the prefrontal cortex in schizophrenia. , 1998, The American journal of psychiatry.

[39]  Derek K. Jones,et al.  Diffusion‐tensor MRI: theory, experimental design and data analysis – a technical review , 2002 .

[40]  Carl-Fredrik Westin,et al.  Spatial normalization of diffusion tensor MRI using multiple channels , 2003, NeuroImage.

[41]  S. Lawrie,et al.  Diffusion tensor imaging (DTI) and proton magnetic resonance spectroscopy (1H MRS) in schizophrenic subjects and normal controls , 2001, Psychiatry Research: Neuroimaging.

[42]  K. Krishnan,et al.  Evidence of white matter tract disruption in MRI hyperintensities , 2001, Biological Psychiatry.

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

[44]  T. Kinoshita,et al.  Diffusion Tensor Magnetic Resonance Imaging of Disruption of Regional White Matter in Schizophrenia , 2003, Neuropsychobiology.

[45]  Derek K. Jones,et al.  Age effects on diffusion tensor magnetic resonance imaging tractography measures of frontal cortex connections in schizophrenia , 2006, Human brain mapping.

[46]  M. Kubicki,et al.  Neuropsychological correlates of diffusion tensor imaging in schizophrenia. , 2004, Neuropsychology.

[47]  Michael Sanfilipo,et al.  Inferior frontal white matter anisotropy and negative symptoms of schizophrenia: a diffusion tensor imaging study. , 2003, The American journal of psychiatry.

[48]  H. Gu,et al.  Circular spectrum mapping for intravoxel fiber structures based on high angular resolution apparent diffusion coefficients , 2003, Magnetic resonance in medicine.

[49]  M. Horsfield,et al.  Optimal strategies for measuring diffusion in anisotropic systems by magnetic resonance imaging , 1999, Magnetic resonance in medicine.

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

[51]  S C Williams,et al.  Generic brain activation mapping in functional magnetic resonance imaging: a nonparametric approach. , 1997, Magnetic resonance imaging.

[52]  Roland Bammer,et al.  Diffusion tensor imaging using single‐shot SENSE‐EPI , 2002, Magnetic resonance in medicine.

[53]  R. Heaton Wisconsin Card Sorting Test manual , 1993 .

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

[55]  Nunzio Pomara,et al.  Reduced frontal white matter integrity in cocaine dependence: a controlled diffusion tensor imaging study , 2002, Biological Psychiatry.

[56]  V. Schmithorst,et al.  Cognitive functions correlate with white matter architecture in a normal pediatric population: A diffusion tensor MRI study , 2005, Human brain mapping.

[57]  D. Parker,et al.  Analysis of partial volume effects in diffusion‐tensor MRI , 2001, Magnetic resonance in medicine.

[58]  A. Alexander,et al.  Does fractional anisotropy have better noise immunity characteristics than relative anisotropy in diffusion tensor MRI? An analytical approach , 2004, Magnetic resonance in medicine.

[59]  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.

[60]  P. Basser,et al.  Diffusion tensor MR imaging of the human brain. , 1996, Radiology.

[61]  V. Haughton,et al.  Diffusion tensor MR imaging in diffuse axonal injury. , 2002, AJNR. American journal of neuroradiology.

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

[63]  Geoff J. M. Parker,et al.  Characterizing function–structure relationships in the human visual system with functional MRI and diffusion tensor imaging , 2004, NeuroImage.

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

[65]  Joseph A Maldjian,et al.  Diffusion anisotropy in the corpus callosum. , 2002, AJNR. American journal of neuroradiology.

[66]  W. Strik,et al.  Reduced hippocampal anisotropy related to anteriorization of alpha EEG in schizophrenia , 2003, Neuroreport.

[67]  P. Basser,et al.  Toward a quantitative assessment of diffusion anisotropy , 1996, Magnetic resonance in medicine.

[68]  M Hedehus,et al.  Diffusion-tensor MR imaging at 1.5 and 3.0 T: initial observations. , 2001, Radiology.

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

[70]  Thomas Dierks,et al.  Volumetry and diffusion tensor imaging of hippocampal subregions in schizophrenia , 2004, Neuroreport.

[71]  C. Sotak,et al.  Multispectral analysis of the temporal evolution of cerebral ischemia in the rat brain , 2000, Journal of magnetic resonance imaging : JMRI.

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

[73]  C. Frith The neural basis of hallucinations and delusions. , 2005, Comptes rendus biologies.

[74]  M. Hoptman,et al.  Frontal white matter microstructure, aggression, and impulsivity in men with schizophrenia: a preliminary study , 2002, Biological Psychiatry.

[75]  G. Barker,et al.  Investigating regional white matter in schizophrenia using diffusion tensor imaging , 2002, Neuroreport.