Activity-dependent modulation of glutamate, glutamine and glutathione in first-episode schizophrenia: A 7T functional
Peter Jeon1, Michael Mackinley2, Kara Dempster3
1Department of Medical Biophysics, Western University, London, Canada; Lawson Health Research Institute, Imaging Division, London, Canada.
Background And Hypothesis:
Glutamatergic abnormalities have been implicated as an important component of schizophrenia symptoms. Functional magnetic resonance spectroscopy (fMRS) has emerged as a strong candidate for making dynamic observations of neurometabolites, overcoming the challenges of single-state observations in traditional magnetic resonance spectroscopy studies. To date, dynamic measurements of glutathione have not been presented in patients in the early stages of schizophrenia.
Study Design:
Dynamic glutamate, glutamine, and glutathione concentrations were quantified from the dorsal anterior cingulate cortex of 33 first-episode schizophrenia and 23 healthy control volunteers. A four-block 7 T fMRS paradigm was employed using the color-word Stroop task as the cognitive demand. Non-baseline blocks were also normalized relative to the baseline block for metabolite percentage change observations.
Study Results:
ANOVA revealed significant effects of time, metabolite and time x diagnosis x metabolite. Activation and prolonged elevation of glutathione in response to the cognitive stimuli were observed in healthy controls but only glutamate effects were notable in first-episode schizophrenia. Significantly lower glutamate concentrations during the second recovery blocks in both groups compared to their baseline glutamate levels. Normalized glutamate levels revealed a positive correlation between the recovery 2 block and both PANSS-8 Positive and PANSS-8 General scores.
Conclusions:
A potential inability to mount an appropriate antioxidant response to short-term oxidative stress may occur in the early stages of schizophrenia. A longitudinal study of fMRS is required to better understand the regulation of oxidative stress across the different stages of schizophrenia.
