Clinical and Neuropsychological Correlates of White Matter Abnormalities in Recent Onset Schizophrenia

The objective of this study was to investigate the clinical and neuropsychological correlates of white matter abnormalities in patients with schizophrenia studied early in the course of illness. A total of 33 (21 male/12 female) patients with recent onset schizophrenia and 30 (18 male/12 female) healthy volunteers completed structural and diffusion tensor imaging exams. Patients also received clinical and neuropsychological assessments. Fractional anisotropy (FA) maps were compared between groups in the white matter using a voxelwise analysis following intersubject registration to Talairach space and correlated with functional indices. Compared to healthy volunteers, patients demonstrated significantly (p<0.001, cluster size ⩾100) lower FA within temporal lobe white matter regions corresponding approximately to the right and left uncinate fasciculus, left inferior fronto-occipital fasciculus, and left superior longitudinal fasciculus. There were no areas of significantly higher FA in patients compared to healthy volunteers. Lower FA in the bilateral uncinate fasciculus correlated significantly with greater severity of negative symptoms (alogia and affective flattening), and worse verbal learning/memory functioning. In addition, higher FA in the inferior fronto-occipital fasciculus correlated significantly with greater severity of delusions and hallucinations. White matter abnormalities are evident in patients with schizophrenia early in the course of illness, appearing most robust in left temporal regions. These abnormalities have clinical and neuropsychological correlates, which may be useful in further characterizing structure–function relations in schizophrenia and constraining neurobiological models of the disorder.

[1]  Xiao-Li Meng,et al.  Comparing correlated correlation coefficients , 1992 .

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

[3]  Gareth J Barker,et al.  Gray and white matter brain abnormalities in first-episode schizophrenia inferred from magnetization transfer imaging. , 2003, Archives of general psychiatry.

[4]  J N Giedd,et al.  Quantitative morphology of the cerebellum and fourth ventricle in childhood-onset schizophrenia. , 1997, The American journal of psychiatry.

[5]  D. Javitt,et al.  Voxelwise correlational analyses of white matter integrity in multiple cognitive domains in schizophrenia. , 2006, The American journal of psychiatry.

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

[7]  Jim Mintz,et al.  Dysregulated brain development in adult men with schizophrenia: a magnetic resonance imaging study , 2003, Biological Psychiatry.

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

[9]  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.

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

[11]  R. McCarley,et al.  An MRI study of temporal lobe abnormalities and negative symptoms in chronic schizophrenia , 2002, Schizophrenia Research.

[12]  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.

[13]  P. Szeszko,et al.  MRI atlas of human white matter , 2006 .

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

[15]  R. Kikinis,et al.  Planum temporale and Heschl gyrus volume reduction in schizophrenia: a magnetic resonance imaging study of first-episode patients. , 2000, Archives of general psychiatry.

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

[17]  D. Robinson,et al.  Randomized comparison of olanzapine versus risperidone for the treatment of first-episode schizophrenia: 4-month outcomes. , 2006, The American journal of psychiatry.

[18]  P. Basser Inferring microstructural features and the physiological state of tissues from diffusion‐weighted images , 1995, NMR in biomedicine.

[19]  Manzar Ashtari,et al.  White matter abnormalities in obsessive-compulsive disorder: a diffusion tensor imaging study. , 2005, Archives of general psychiatry.

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

[21]  N. Uranova,et al.  Electron microscopy of oligodendroglia in severe mental illness , 2001, Brain Research Bulletin.

[22]  J. Lieberman,et al.  Neuropsychology of first-episode schizophrenia: initial characterization and clinical correlates. , 2000, The American journal of psychiatry.

[23]  Ethan M. Goldberg,et al.  Smaller anterior hippocampal formation volume in antipsychotic-naive patients with first-episode schizophrenia. , 2003, The American journal of psychiatry.

[24]  Gareth J. Barker,et al.  Diffusion tensor imaging in schizophrenia , 2008, European Psychiatry.

[25]  B. Ardekani,et al.  A Fully Automatic Multimodality Image Registration Algorithm , 1995, Journal of computer assisted tomography.

[26]  D. Javitt,et al.  BRAIN IMAGING NEUROREPORT , 2005 .

[27]  Babak A. Ardekani,et al.  Quantitative comparison of algorithms for inter-subject registration of 3D volumetric brain MRI scans , 2005, Journal of Neuroscience Methods.

[28]  T. Lencz,et al.  Generalized and Specific Neurocognitive Deficits in Prodromal Schizophrenia , 2006, Biological Psychiatry.

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

[30]  Jonathan D. Cohen,et al.  Improved Assessment of Significant Activation in Functional Magnetic Resonance Imaging (fMRI): Use of a Cluster‐Size Threshold , 1995, Magnetic resonance in medicine.

[31]  Derek K. Jones,et al.  A diffusion tensor imaging study of fasciculi in schizophrenia. , 2007, The American journal of psychiatry.

[32]  T. Crow,et al.  Twin studies of psychosis and the genetics of cerebral asymmetry , 1999, British Journal of Psychiatry.

[33]  Nina Kohn,et al.  Neurocognitive Profile in Adolescents with Early-Onset Schizophrenia: Clinical Correlates , 2005, Biological Psychiatry.

[34]  Jeffrey A. Lieberman,et al.  Anterior hippocampal volume reductions predict frontal lobe dysfunction in first episode schizophrenia , 1995, Schizophrenia Research.

[35]  Adam M. Brickman,et al.  Internal capsule, corpus callosum and long associative fibers in good and poor outcome schizophrenia: A diffusion tensor imaging survey , 2007, Schizophrenia Research.

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

[37]  R Kikinis,et al.  Left planum temporale volume reduction in schizophrenia. , 1999, Archives of general psychiatry.

[38]  R. Carp,et al.  A neuronal cell line that does not express either prion or doppel proteins , 2005, Neuroreport.

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

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

[41]  J. Lieberman,et al.  Longitudinal assessment of methylphenidate effects on oral word production and symptoms in first-episode schizophrenia at acute and stabilized phases , 1999, Biological Psychiatry.

[42]  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.

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

[44]  J. Rapoport,et al.  Three-dimensional cortical morphometry of the planum temporale in childhood-onset schizophrenia. , 1997, The American journal of psychiatry.

[45]  N. Geschwind,et al.  Human Brain: Cytoarchitectonic Left-Right Asymmetries in the Temporal Speech Region , 1978 .

[46]  Patrick R Hof,et al.  Loss and altered spatial distribution of oligodendrocytes in the superior frontal gyrus in schizophrenia , 2003, Biological Psychiatry.

[47]  Peter B. Jones,et al.  Oligodendrocyte dysfunction in schizophrenia and bipolar disorder , 2003, The Lancet.

[48]  W H Wong,et al.  Genome-wide expression analysis reveals dysregulation of myelination-related genes in chronic schizophrenia , 2001, Proceedings of the National Academy of Sciences of the United States of America.

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

[50]  Vincent Magnotta,et al.  Progressive structural brain abnormalities and their relationship to clinical outcome: a longitudinal magnetic resonance imaging study early in schizophrenia. , 2003, Archives of general psychiatry.

[51]  Markus Kiefer,et al.  Semantic and syntactic processes during sentence comprehension in patients with schizophrenia: evidence from event-related potentials , 2003, Schizophrenia Research.

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

[53]  Elena Antonova,et al.  The relationship between brain structure and neurocognition in schizophrenia: a selective review , 2004, Schizophrenia Research.

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

[55]  Philip D. Harvey,et al.  White matter changes in schizophrenia: evidence for myelin-related dysfunction. , 2003, Archives of general psychiatry.

[56]  Jeffrey A Lieberman,et al.  Neuropsychological correlates of hippocampal volumes in patients experiencing a first episode of schizophrenia. , 2002, The American journal of psychiatry.