Volumetric white matter abnormalities in first-episode schizophrenia: a longitudinal, tensor-based morphometry study.

OBJECTIVE While schizophrenia has long been considered a disorder of brain connectivity, few studies have investigated white matter abnormalities in patients with first-episode schizophrenia, and even fewer studies have investigated whether there is progressive white matter pathology in the disease. METHOD The authors obtained a T1-weighted structural magnetic resonance imaging (MRI) scan on 41 patients with first-episode schizophrenia. These first-episode schizophrenia patients were analyzed relative to 47 age- and sex-matched healthy comparison subjects who also underwent an MRI scan. Of the baseline participants, 25 first-episode schizophrenia patients and 26 comparison subjects returned 2 to 3 years later for a follow-up scan. To identify regional volumetric white matter differences between the two groups at baseline, voxel-based morphometry in statistical parametric mapping-2 (SPM2) was used, while tensor-based morphometry was used to identify the longitudinal changes over the follow-up interval. RESULTS The first-episode schizophrenia patients exhibited volumetric deficits in the white matter of the frontal and temporal lobes at baseline, as well as volumetric increases in the white matter of the frontoparietal junction bilaterally. Furthermore, these first-episode schizophrenia patients lost considerably more white matter over the follow-up interval relative to comparison subjects in the middle and inferior temporal cortex bilaterally. CONCLUSIONS These results indicate that patients with schizophrenia exhibit white matter abnormalities at the time of their first presentation of psychotic symptoms to mental health services and that these abnormalities degenerate further over the initial years of illness. Given the role that white matter plays in neural communication, the authors suggest that these white matter abnormalities may be a cause of the dysfunctional neural connectivity that has been proposed to underlie the symptoms of schizophrenia.

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

[2]  John Brennan,et al.  Progressive grey matter atrophy over the first 2–3 years of illness in first-episode schizophrenia: A tensor-based morphometry study , 2006, NeuroImage.

[3]  Ian B. Hickie,et al.  Sphere: A National Depression Project , 1998 .

[4]  M. Sendtner,et al.  Does oligodendrocyte survival depend on axons? , 1993, Current Biology.

[5]  J. Lieberman,et al.  Longitudinal study of brain morphology in first episode schizophrenia , 2001, Biological Psychiatry.

[6]  Evian Gordon,et al.  Clinical Profiles, Scope and General Findings of the Western Sydney First Episode Psychosis Project , 2005, The Australian and New Zealand journal of psychiatry.

[7]  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.

[8]  R Kikinis,et al.  Prefrontal gray matter volume reduction in first episode schizophrenia. , 2001, Cerebral cortex.

[9]  J. Rapoport,et al.  Progressive cortical change during adolescence in childhood-onset schizophrenia. A longitudinal magnetic resonance imaging study. , 1999, Archives of general psychiatry.

[10]  P. Lovibond,et al.  The structure of negative emotional states: comparison of the Depression Anxiety Stress Scales (DASS) with the Beck Depression and Anxiety Inventories. , 1995, Behaviour research and therapy.

[11]  Muriel Walshe,et al.  Regional volume deviations of brain structure in schizophrenia and psychotic bipolar disorder , 2005, British Journal of Psychiatry.

[12]  Tyrone D. Cannon,et al.  Structural magnetic resonance imaging in patients with first-episode schizophrenia, psychotic and severe non-psychotic depression and healthy controls , 2002, British Journal of Psychiatry.

[13]  R. Coppola,et al.  Functional and effective frontotemporal connectivity and genetic risk for schizophrenia , 2003, Biological Psychiatry.

[14]  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 .

[15]  M Cercignani,et al.  Diffusion tensor magnetic resonance imaging in multiple sclerosis , 2001, Neurology.

[16]  Thomas J. Whitford,et al.  Grey matter deficits and symptom profile in first episode schizophrenia , 2005, Psychiatry Research: Neuroimaging.

[17]  R. Kahn,et al.  Brain volume changes in first-episode schizophrenia: a 1-year follow-up study. , 2002, Archives of general psychiatry.

[18]  R. Kahn,et al.  Brain morphology in antipsychotic-naïve schizophrenia: A study of multiple brain structures , 2002, British Journal of Psychiatry.

[19]  P. Goldman-Rakic,et al.  The reduced neuropil hypothesis: a circuit based model of schizophrenia , 1999, Biological Psychiatry.

[20]  M Cortsen,et al.  Progressive atrophy of the frontal lobes in first‐episode schizophrenia: interaction with clinical course and neuroleptic treatment , 1999, Acta psychiatrica Scandinavica.

[21]  Karl J. Friston,et al.  Reduced frontotemporal functional connectivity in schizophrenia associated with auditory hallucinations , 2002, Biological Psychiatry.

[22]  T. Whitford,et al.  Diagnosis-Related Regional Gray Matter Loss Over Two Years in First Episode Schizophrenia and Bipolar Disorder , 2005, Biological Psychiatry.

[23]  D. Wolpert,et al.  Explaining the symptoms of schizophrenia: Abnormalities in the awareness of action , 2000, Brain Research Reviews.

[24]  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.

[25]  B. Pakkenberg,et al.  Total nerve cell number in neocortex in chronic schizophrenics and controls estimated using optical disectors , 1993, Biological Psychiatry.

[26]  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.

[27]  T. Wassink,et al.  Defining the phenotype of schizophrenia: cognitive dysmetria and its neural mechanisms , 1999, Biological Psychiatry.

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

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

[30]  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.

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

[32]  L. Opler,et al.  The Positive and Negative Syndrome Scale (PANSS): Rationale and Standardisation , 1989, British Journal of Psychiatry.

[33]  Karl J. Friston,et al.  Image registration using a symmetric prior—in three dimensions , 1999, Human brain mapping.

[34]  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.

[35]  Karl J. Friston The disconnection hypothesis , 1998, Schizophrenia Research.

[36]  J. Ashburner,et al.  Progression of structural neuropathology in preclinical Huntington’s disease: a tensor based morphometry study , 2005, Journal of Neurology, Neurosurgery & Psychiatry.

[37]  A. Baddeley,et al.  The Spot-the-Word test: a robust estimate of verbal intelligence based on lexical decision. , 1993, The British journal of clinical psychology.

[38]  George Bartzokis,et al.  Schizophrenia: Breakdown in the Well-regulated Lifelong Process of Brain Development and Maturation , 2002, Neuropsychopharmacology.