All ETDs from UAB

Advisory Committee Chair

Adrienne C Lahti

Advisory Committee Members

Edwin W Cook

Rajesh K Kana

David C Knight

Kristina M Visscher

Document Type

Dissertation

Date of Award

2018

Degree Name by School

Doctor of Philosophy (PhD) College of Arts and Sciences

Abstract

Schizophrenia is a mental disorder that affects around 1% of the world’s population. Antipsychotic medication does not effectively treat all symptoms as around 1/3 of those diagnosed will remain unresponsive to treatment. Patients with schizophrenia (SZ) present dysfunction in cognitive control processes compared to healthy controls (HC). Neuroimaging SZ studies report abnormalities in brain function and neurochemistry, although the majority of these studies involve medicated patients. To better determine SZ brain abnormalities, it is vital to characterize brain function without the confounding effect of antipsychotic medication, determine the extent of medication’s effects on brain function, and the relationship with symptom improvement. The goal of this dissertation was to examine functional and neurochemical abnormalities in unmedicated SZ, the changes following antipsychotic medication administration, and the relationship with treatment response using the neuroimaging techniques of functional magnetic resonance imaging (fMRI) and magnetic resonance spectroscopy (MRS). In the first study, we conducted a task-based fMRI blood oxygen level-dependent (BOLD) study in SZ and HC, at unmedicated baseline and after 6 weeks of antipsychotic drug (APD), and found that unmedicated SZ showed decreased BOLD signal within regions of the cognitive control network during Stroop performance. We also found alterations in network regions after 6 weeks that can be attributed to medication and that baseline BOLD signal predicted treatment response. In the second study, we measured functional connectivity within regions of the cognitive control network in SZ and HC, at unmedicated baseline and after 6 weeks APD. We found that unmedicated SZ showed altered functional connectivity, both greater and lower, between the anterior cingulate cortex (ACC) and brain regions comprising the cognitive control network compared to HC and that after 6 weeks of medication the connectivity decreased. Also, we found that baseline SZ functional connectivity was predictive of treatment response. In the final study, we combined the previous Stroop task-based BOLD fMRI and MRS in unmedicated SZ and HC, baseline and after 6 weeks APD, and found that HC had significant correlations between glutamate+glutamine/creatine (Glx/Cr) and Stroop BOLD signal in the ACC and precuneus that was not found in unmedicated SZ and that following 6 weeks, SZ showed a more positive relationship.

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