A Diffusion Tensor Imaging Study of White Matter in Early-Onset Schizophrenia

BACKGROUND Voxel-based analysis of diffusion tensor magnetic resonance imaging (DTI) data was used to examine white matter integrity in adolescents with early-onset schizophrenia (EOS), defined as schizophrenia beginning before the 18th birthday. METHODS Nineteen patients with EOS, aged 13 to 19, were compared with 20 healthy volunteers matched for age, gender, and parental socioeconomic status. Diffusion tensor magnetic resonance imaging data were acquired on a GE Signa NVi 1.5 Tesla system (General Electric, Milwaukee, Wisconsin). Maps of fractional anisotropy (FA) were registered into standard space, and group differences were examined using a nonparametric statistical approach. RESULTS In comparison with healthy participants, EOS patients had significantly lower FA in the white matter of the parietal association cortex bilaterally and in the left middle cerebellar penduncle. No areas with significantly higher FA in patients were identified. CONCLUSIONS Parietal and cerebellar white matter abnormalities may contribute to the emergence of psychotic symptoms in adolescence.

[1]  P. Basser,et al.  Estimation of the effective self-diffusion tensor from the NMR spin echo. , 1994, Journal of magnetic resonance. Series B.

[2]  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.

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

[4]  T. Crow,et al.  Regional deficits in brain volume in schizophrenia: a meta-analysis of voxel-based morphometry studies. , 2005, The American journal of psychiatry.

[5]  Kelvin O. Lim,et al.  Disruption of hippocampal connectivity in children and adolescents with schizophrenia — A voxel-based diffusion tensor imaging study , 2007, Schizophrenia Research.

[6]  Jeremy D Schmahmann,et al.  Dysmetria of thought: clinical consequences of cerebellar dysfunction on cognition and affect , 1998, Trends in Cognitive Sciences.

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

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

[9]  Nancy C Andreasen,et al.  Cerebellar morphology as a predictor of symptom and psychosocial outcome in schizophrenia , 1999, Biological Psychiatry.

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

[11]  D. Garver,et al.  State-related changes in cerebral white matter may underlie psychosis exacerbation , 2004, Psychiatry Research: Neuroimaging.

[12]  D. Pandya,et al.  Architecture and Connections of Cortical Association Areas , 1985 .

[13]  Surveys.,et al.  Standard occupational classification , 1990 .

[14]  F. Benes,et al.  Emerging principles of altered neural circuitry in schizophrenia , 2000, Brain Research Reviews.

[15]  Karl J. Friston,et al.  A Voxel-Based Morphometric Study of Ageing in 465 Normal Adult Human Brains , 2001, NeuroImage.

[16]  P. Maruff,et al.  Attention, motor control and motor imagery in schizophrenia: implications for the role of the parietal cortex , 2004, Schizophrenia Research.

[17]  M. Annett.  A classification of hand preference by association analysis. , 1970, British journal of psychology.

[18]  Sophia Frangou,et al.  Increased developmental deviance and premorbid dysfunction in early onset schizophrenia , 2003, Schizophrenia Research.

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

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

[21]  C. Frith,et al.  Self-awareness and action , 2003, Current Opinion in Neurobiology.

[22]  N. Makris,et al.  Cortical abnormalities in schizophrenia identified by structural magnetic resonance imaging. , 1999, Archives of general psychiatry.

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

[24]  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.

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

[26]  J. Rapoport,et al.  Mapping adolescent brain change reveals dynamic wave of accelerated gray matter loss in very early-onset schizophrenia , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[27]  D. Weinberger,et al.  A neurodevelopmental model of schizophrenia: Neonatal disconnection of the hippocampus , 2009, Neurotoxicity Research.

[28]  J. McClellan,et al.  Clinical features and outcome of child and adolescent schizophrenia. , 1994, Schizophrenia bulletin.

[29]  J. Rapoport,et al.  Childhood onset schizophrenia: cortical brain abnormalities as young adults. , 2006, Journal of child psychology and psychiatry, and allied disciplines.

[30]  M. Raichle,et al.  Subgenual prefrontal cortex abnormalities in mood disorders , 1997, Nature.

[31]  Joel Jeffries,et al.  Clinical Handbook of Psychotropic Drugs , 1994 .

[32]  Thomas F. Nugent,et al.  Dynamic mapping of human cortical development during childhood through early adulthood. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[33]  Paul J. Harrison,et al.  Schizophrenia genes, gene expression, and neuropathology: on the matter of their convergence , 2005, Molecular Psychiatry.

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

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

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

[37]  Godfrey D Pearlson,et al.  Morphometric assessment of the heteromodal association cortex in schizophrenia. , 2004, The American journal of psychiatry.

[38]  Philip K. McGuire,et al.  Diffusion Tensor Imaging in Schizophrenia , 2005, Biological Psychiatry.