Brain Advance Access originally published online on August 13, 2007
Brain 2007 130(9):2375-2386; doi:10.1093/brain/awm184
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Anatomically related grey and white matter abnormalities in adolescent-onset schizophrenia
1FMRIB Centre, Department of Clinical Neurology, University of Oxford, John Radcliffe Hospital, Oxford, 2Highfield Adolescent Unit, Warneford Hospital, Oxford, 3GlaxoSmithKline Clinical Imaging Centre, Hammersmith Hospital and Department of Clinical Neurosciences, Imperial College, London and 4Department of Experimental Psychology, University of Oxford, UK
Correspondence to: Dr Gwenaëlle Douaud, FMRIB Centre, University of Oxford, John Radcliffe Hospital, Headington, OX3 9DU, Oxford, UK E-mail: douaud{at}fmrib.ox.ac.uk
Adolescent-onset schizophrenia provides an exceptional opportunity to explore the neuropathology of schizophrenia free from the potential confounds of prolonged periods of medication and disease interactions with age-related neurodegeneration. Our aim was to investigate structural grey and white matter abnormalities in adolescent-onset schizophrenia. Whole-brain voxel-wise investigation of both grey matter topography and white matter integrity (Fractional Anisotropy) were carried out on 25 adolescent-onset schizophrenic patients and 25 healthy adolescents. We employed a refined voxel-based morphometry-like approach for grey matter analysis and the recently introduced method of tract-based spatial statistics (TBSS) for white matter analysis. Both kinds of studies revealed widespread abnormalities characterized by a lower fractional anisotropy neuroanatomically associated with localized reduced grey matter in the schizophrenic group. The grey matter changes can either be interpreted as the result of a locally reduced cortical thickness or as a manifestation of different patterns of gyrification. There was a widespread reduction of anisotropy in the white matter, especially in the corpus callosum. We speculate that the anisotropy changes relate to the functional changes in brain connectivity that are thought to play a central role in the clinical expression of the disease. The distribution of grey matter changes was consistent with clinical features of the disease. For example, grey and white matter abnormalities found in the Heschl's gyrus, the parietal operculum, left Broca's area and the left arcuate fasciculus (similar to previous findings in adult-onset schizophrenia) are likely to relate to functional impairments of language and auditory perception. In addition, in contrast to earlier studies, we found striking abnormalities in the primary sensorimotor and premotor cortices and in white matter tracts susbserving motor control (mainly the pyramidal tract). This novel finding suggests a new potential marker of altered white matter maturation specific to adolescent-onset schizophrenia. Together, our observations suggest that the neuropathology of adolescent-onset schizophrenia involves larger and widespread changes than in the adult form, consistent with the greater clinical severity.
Key Words: schizophrenia; age of onset; voxel-based morphometry; diffusion tensor imaging; pyramidal tract
Abbreviations: DLPFC, dorso-lateral prefrontal cortex; DTI, diffusion tensor imaging; FA, fractional anisotropy; FEF, frontal eye field; FSL, FMRIB (functional magnetic resonance imaging of the brain centre) software library; IRTK, image registration toolkit; MD, mean diffusivity; ROI, region of interest; SMA, supplementary motor area; SPM, statistical parametric mapping; TBSS, tract-based spatial statistics; VBM, voxel-based morphometry; BA, Brodmann area.
Received April 4, 2007. Revised July 3, 2007. Accepted July 10, 2007.
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