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Title: Brain abnormalities in schizophrenia : evidence from neuropathologically sensitive MRI techniques
Author: Foong, Jacqueline
ISNI:       0000 0001 3472 9156
Awarding Body: University of London
Current Institution: University College London (University of London)
Date of Award: 2002
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Post mortem and structural imaging studies in schizophrenia have reported macroscopic changes such as global and regional volume reductions but it has been more difficult to characterise the histopathological changes that underlie these abnormalities. The aim of this thesis was to further investigate white matter and cortical abnormalities in patients with schizophrenia using novel neuroimaging techniques, namely magnetization transfer imaging (MTI) and diffusion tensor imaging (DTI) that are more sensitive to neuropathological changes in vivo than conventional MRI. Studies of white matter abnormalities Study 1 MTI was performed in 25 schizophrenic patients and 30 healthy controls to examine white matter using a region of interest (ROI) approach to measure magnetization transfer ratios (MTR). MTR was significantly reduced in bilateral temporal white matter but not in other regions of white matter in schizophrenic patients compared to controls. Clinical variables such as age, duration of symptoms, schizophrenic symptomatology and soft neurological signs did not predict the reduction in MTR. However, the pattern of correlations between the left and right frontal MTR values was different in the patients compared to controls suggesting that subtle abnormalities in interhemispheric connections may be present in schizophrenia. This study demonstrates that subtle white matter pathology restricted to the temporal lobes can be detected in schizophrenic patients using MTI and are most likely related to myelin and axonal abnormalities. Study 2 DTI was used to investigate white matter abnormalities in 20 schizophrenic patients who were compared to 25 healthy controls. DTI changes were detected in the corpus callosum, specifically in the splenium but not the genu, suggesting that there may be a focal disruption of commisural connectivity in schizophrenia. In contrast, no DTI changes in other regions of white matter could be detected in a subgroup of these patients using a voxel-based analysis. Study of cortical abnormalities Study 3 Cortical abnormalities in the same group of patients and controls from Study 1 were examined using MTI. A voxel-based analysis revealed widespread MTR reductions in the cortex unrelated to volume reduction, particularly in the frontal and temporal regions, in the schizophrenic patients. The MTR reductions only extended into the white matter in the temporal lobes and not other regions. Reduced MTR in bilateral parieto-occipital cortex and the genu of the corpus callosum was associated with the severity of negative symptoms in the patients. These findings suggest that subtle neuropathological changes in the cortex can be detected in schizophrenia using MTI. Together, the results from the three studies suggest that the detectable pathology in schizophrenia is predominantly cortical. The cortical changes are widespread but preferentially involve the fronto-temporal regions. It is likely that abnormal connectivity in schizophrenia is mainly related to cortical changes with little gross disruption of white matter tracts. These studies also illustrate the potential use of MTI and DTI to investigate the neuropathology of schizophrenia although methodological issues relating to their data acquisition and analysis should be carefully considered.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Medicine