Activity-dependent modulation of glutamate, glutamine and glutathione in first-episode schizophrenia: A 7T functional MRS study.

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.