Functional magnetic resonance spectroscopy of glutamate in schizophrenia and major depressive disorder: anterior cingulate activity during a color-word Stroop task

Background: Glutamate abnormalities have been suggested to be associated with symptoms of schizophrenia. Using functional magnetic resonance spectroscopy ( 1 H-fMRS), it is possible to monitor glutamate dynamically in the activated brain areas, which has yet to be reported in schizophrenia. It was hypothesized that subjects with schizophrenia would have weaker glutamatergic responses in the anterior cingulate to a color-word Stroop Task. AIMS: The aim of this study was to gain insight into the health of GLU neurotransmission and the GLU-GLN cycle in SZ using a 1 H-fMRS protocol. Methods: Spectra were acquired from the anterior cingulate of 16 participants with schizophrenia, 16 healthy controls and 16 participants with major depressive disorder (MDD) while performing the Stroop task in a 7T magnetic resonance imaging scanner. 1 H-fMRS spectra were acquired for 20 min in which there were three 4-min blocks of cross fixation interleaved with two 4-min blocks of the Stroop paradigm. Results: A repeated-measures analysis of variance revealed a main effect of time for glutamate concentrations of all groups ( P <0.001). The healthy control group increased glutamate concentrations in the first run of the Stroop task ( P =0.006) followed by a decrease in the recovery period ( P =0.007). Neither the schizophrenia ( P =0.107) nor MDD ( P =0.081) groups had significant glutamate changes in the first run of the task, while the schizophrenia group had a significant increase in glutamine ( P =0.005). The MDD group decreased glutamate concentrations in the second run of the task ( P =0.003), as did all the groups combined ( P =0.003). Conclusions: 1 H-fMRS data were successfully acquired from psychiatric subjects with schizophrenia and mood disorder using a cognitive paradigm for the first time. Future study designs should further elucidate the glutamatergic response to functional activation in schizophrenia.