All ETDs from UAB

Advisory Committee Chair

Adrienne C Lahti

Advisory Committee Members

Allan C Dobbins

James H Meador-Woodruff

Andrew E Pollard

Kristina M Visscher

Document Type

Dissertation

Date of Award

2013

Degree Name by School

Doctor of Philosophy (PhD) School of Engineering

Abstract

Schizophrenia is a complex, often debilitating chronic mental disorder that affects approximately 1% of people worldwide. Recently, there has been growing interest in identifying non-invasive biomarkers of schizophrenia. Understanding the molecular and structural mechanisms underlying clinical features of schizophrenia and patients' drug response is an important step in identifying biomarkers and potential targets for novel medications, treatment strategies, and interventions. The primary objective of this dissertation research was to use non-invasive magnetic resonance imaging techniques, specifically magnetic resonance spectroscopy (MRS) and diffusion tensor imaging (DTI), to examine the neurochemical and structural correlates of symptoms, cognition, and treatment response to antipsychotic medication in patients with schizophrenia. Based on our previous work, we focused on the mesocorticolimbic regions and their related white matter connections. In the first study, we demonstrated the feasibility of acquiring single-voxel MRS measurements at 3T from the substantia nigra of patients with schizophrenia and healthy controls. We found a positive correlation between glutamate and cognition in controls but not schizophrenia patients, demonstrating the utility of MRS for investigating neurometabolite abnormalities underlying cognitive dysfunction in schizophrenia. In the second study, we used MRS to test the hypothesis that antipsychotic treatment alters glutamate, N-acetylaspartate, and the glutamate/N-acetylaspartate ratio in the anterior cingulate cortex (ACC) and hippocampus of patients with schizophrenia. We found that regionally specific glutamate abnormalities are present in unmedicated patients and that antipsychotic medication appears to modulate glutamate function in a manner that is regionally specific. We also demonstrated that glutamatergic measurements may become useful trait markers and predictors of treatment response. In the third study, we used DTI to assess white matter integrity and proton MRS to assess neuronal integrity in the ACC and hippocampus. We found widespread white matter abnormalities in patients with schizophrenia that appear to be driven by loss of myelin integrity. We also demonstrated the utility of a multi-modal neuroimaging approach to help further our understanding of the relationship between white matter microstructure and neurochemistry in distinct regions connected by white matter tracts.

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