Doctor of Philosophy
Dr. Peter C. Williamson and Dr. Terry Thompson
Approximately one in hundred people suffer from schizophrenia. Current medications partially improve the symptoms. There is no cure. Glutamate, an excitatory neurotransmitter, is a possible cause of the schizophrenia symptoms. Excessive glutamate release eventually leads to neurodegeneration. Longitudinal studies are necessary to observe the neurodegenerative process.
Seventeen schizophrenia patients and 17 healthy volunteers underwent proton magnetic resonance spectroscopy (MRS) and imaging to measure neurochemical and structural changes in vivo. Metabolite levels were measured from a 1.5cm3 voxel in the anterior cingulate and thalamus using the stimulated echo acquisition mode sequence. Gray matter (GM) was assessed with voxel-based morphometry and ANALYZE.
Total glutamatergic metabolite (tGL), N-acetylaspartate (NAA), and GM were significantly decreased in schizophrenia over 80 months. Reduced tGL and NAA levels were significantly correlated with GM changes. tGL loss was negatively correlated with social functioning. Significantly decreased tGL levels were possibly associated with GM loss in the spectroscopy voxel. Metabolite signal-to-noise ratio, but not quantification, was decreased as a function of MR system age.
These findings demonstrate the feasibility of long-term MRS studies and implications for the pathophysiology of schizophrenia. tGL and GM losses were consistent with neurodegeneration but the effects of an early neurodevelopmental lesion or the effects of chronic medication cannot be ruled out. Structural and metabolite changes in these patients implicate glutamate as a possible target of medication in this disorder. The association between tGL loss and social functioning suggests it might be possible to arrest deterioration with pharmaceuticals that target glutamate.
Aoyama, Naoko, "Glutamatergic Metabolites and Gray Matter Losses in Schizophrenia: A Longitudinal Study Using In Vivo Proton Magnetic Resonance Spectroscopy" (2011). Electronic Thesis and Dissertation Repository. 151.