Date of Award


Degree Type


Degree Name

Doctor of Philosophy


Schizophrenia is a brain disease that affects about one in every 100 Canadians. Approximately 40% of patients affected with schizophrenia have a lifelong debilitating illness. Numerous studies have been conducted yet, the pathophysiology of this disease is still unclear. Magnetic resonance spectroscopy (MRS) is a noninvasive technique that provides a biochemical analysis of living tissue from a defined region in the brain, which is not possible with any other technique. Consequently, MRS opens a new window into the research of schizophrenia.;Quantifying the metabolite levels observed in in vivo {dollar}\sp1{dollar}H MR spectra acquired with a short echo time sequence is problematic due to complex overlapping resonances. A technique was developed to quantify these metabolites with the input of a priori knowledge of the individual metabolites into a spectral lineshape fitting routine. The accuracy and precision of modelling these metabolites were investigated with simulated spectra of varying signal-to-noise ratios and relative metabolite levels. The efficacy of this technique was then tested on repeated in vivo measures. The coefficients of variation were less than 10% for N-acetylaspartate, phosphocreatine plus creatine and choline, and approximately 20% for glutamate.;In vivo {dollar}\sp1{dollar}H and phosphorus {dollar}(\sp{lcub}31{rcub}{dollar}P) MR spectra from the left dorsolateral prefrontal region of first episode drug-naive (DN), newly-diagnosed medicated (NDM) and chronic medicated (CM) schizophrenia patients were acquired and compared to controls of similar gender, education, parental education and handedness. The {dollar}\sp1{dollar}H results suggest the resting glutamate level and neuronal cell viability are not altered in the DN or CM patients. In the NDM patients, the altered glutamate and glutamine levels would suggest that the neuroleptic medication increases the presynaptic glutamate release. The increased glutamine level of the CM patients (which correlated with the length of illness) may suggest that glia volume increases as the illness progresses.;In the {dollar}\sp{lcub}31{rcub}{dollar}P study, alterations in the membrane phospholipid metabolism were observed in the DN patients compared to controls. No differences in the high-energy phosphate metabolite levels were observed in the patients, except for decreased inorganic orthophosphate levels in the NDM patients. The intracellular free magnesium concentration was higher in all three patient groups compared to controls.



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