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Title: Structural brain imaging in schizophrenia : contemporary issues
Author: Steel, Robby M.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2004
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In the first section of this thesis structural brain imaging is presented as a powerful tool for investigating the biological correlates of schizophrenia, thereby informing the ongoing evolution of the concept. The major pathophysiological hypotheses of schizophrenia are discussed from the perspective of structural brain imaging. The contemporary literature is then reviewed before three potential strategies for future structural imaging research are presented: (1) imaginative clinical study design employing carefully selected sub-groups from within the schizophrenic population; (2) adoption of newly developed approaches to MRI data acquisition and analysis; (3) utilisation of novel structural imaging techniques. In the second part of this thesis three studies are presented, each illustrating one of the strategies described above. Study 1: Structural magnetic resonance imaging (MRI) of the brain in presumed carriers of gene(s) for schizophrenia, their affected and unaffected siblings. The aim of this study was to establish if the gene(s) for schizophrenia are associated with specific abnormalities of brain structure. Six sib-ships from multiple affected families were recruited. Each sib-ship consisted of one patient with schizophrenia, one ‘obligate carrier’ without the disorder but with an affected child and one ‘non-affected non-carrier’. MRI was conducted with a semi-automated region of interest analysis. Between-group comparisons were tested by repeated measures analysis of variance. Reductions in volumes of cortical structures and of whole brain were found only in schizophrenics and therefore appear to be associated with phenotype. In contrast, reduced volume of the amygdalo-hippocampal complex (AHC) was found in both schizophrenics and obligates and therefore appears to be associated with genetic risk for the disorder even in the absence of disease. Reduced AHC volume may therefore represent an endophenotypic marker for schizophrenia. Study 2: A voxel based morphometry (VBM) and region of interest (ROI) analysis of the genotypic and phenotypic neuroanatomy of schizophrenia. The aim of this study was to explore the likely impact of a new method of data analysis upon future structural brain imaging research. The MRI data set from study 1 (above) was analysed using a voxel-based statistical technique (VBM) and a conventional ROI approach. The results obtained by the two methods were then compared. Overall, the results obtained by VBM were compatible with those obtained by ROI. However, the extent of the overlap varied according to the statistical methods employed. Reassuringly, maximal agreement was found when the ‘optimal’, most methodologically appropriate, VBM analysis was compared with the ‘optimal’ ROI analysis (from study 1). Study 3: Diffusion tensor imaging (DTI) and proton magnetic resonance spectroscopy (1H-MRS) in schizophrenic subjects and normal controls. This study was included to illustrate the challenges inherent in the adoption of novel imaging techniques. The study was designed to identify anatomical correlates of functional dysconnectivity between the pre-frontal and temporal regions in schizophrenia.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available