Functional Magnetic Resonance Spectroscopy in First-Episode Schizophrenia: Measuring Glutamate and Glutathione Dynamics at 7-Tesla
Abstract
Schizophrenia is a neuropsychiatric illness without known etiology or cure. Current efforts for symptom treatment still seem to leave a large portion of affected individuals without proper symptom management, with those experiencing symptom relief still having to wrestle with potential side-effects from medication trials. There has been growing evidence suggesting that glutamate and glutathione abnormalities hold major roles in development and manifestation of schizophrenia symptoms.
Magnetic resonance spectroscopy (MRS) provides a non-invasive means to observe in-vivo brain chemistry, including glutamate and glutathione. By adding a functional component to an MRS paradigm (fMRS), such as the color-word Stroop task, it is possible to detect potential changes in brain metabolite levels in response to a cognitive stimulus.
The objectives of this thesis were to determine whether a conventional short echo-time or longer echo-time semi-LASER sequence would be more suitable for measurements of an fMRS paradigm at 7.0-Tesla, and to apply this finding to the study of a group of never-medicated, first-episode schizophrenia (FES) individuals to track any potential abnormal glutamate and glutathione dynamics.
Contrary to previous beliefs that the shortest achievable echo-time would produce the most measurement signal, results from this study found that a long echo time (TE=100ms) produced very similar quality of measurements, with further benefits of long echo time being the removal of any macromolecular signal contribution.
Comparison of healthy controls (n = 25) to a FES population (n = 21) revealed no significant difference in resting or dynamic glutamate levels. However, resting and dynamic glutathione level were significantly different, suggesting potential glutathione regulation abnormalities, and, in extension, although not observed in this study, potential glutamate and glutamine abnormalities.
Future fMRS studies should investigate glutamate and glutathione dynamics from longitudinal data of FES follow-ups as well as between specific sub-groups within FES.