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

Reggie Taylor,Nagalingam Rajakumar,Peter C Williamson,Richard W J Neufeld,Maria Densmore,Betsy Schaefer,Jean Théberge,Elizabeth A Osuch

doi:10.1038/npjschz.2015.28

Reggie Taylor, Nagalingam Rajakumar + Show 6 more

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https://doi.org/10.1038/npjschz.2015.28

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Abstract

Background:Glutamate abnormalities have been suggested to be associated with symptoms of schizophrenia. Using functional magnetic resonance spectroscopy (1H-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 1H-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. 1H-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: 1H-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.

Highlights

Schizophrenia (SZ) has been suggested to be associated with dysfunction in brain areas that utilize glutamate (Glu) for neurotransmission.[1]
Significant family-wise error corrected (Po0.05) activation of the anterior cingulate cortex (ACC) was observed in the confirmatory fMRI (Figure 1c)
There were no significant time by group interactions (Glu, P = 0.377; Gln, P = 0.317; Glx, P = 0.616) and there were no main effects of group (Glu, P = 0.797; Gln, P = 0.137; Glx, P = 0.700)

Summary

Introduction

Schizophrenia (SZ) has been suggested to be associated with dysfunction in brain areas that utilize glutamate (Glu) for neurotransmission.[1]. Proton magnetic resonance spectroscopy (1H-MRS) has demonstrated abnormal brain Glu concentrations, with its metabolic precursor/by-product, glutamine (Gln), in individuals with SZ.[7,8] findings may not be specific to this illness Both major depressive disorder (MDD) and bipolar disorder have demonstrated abnormalities of Glu in multiple brain areas using 1HMRS.[9,10,11] MDD has been consistently reported to have lower glutamatergic metabolites (Glu, Gln, or Glx (Glu+Gln)), bipolar disorder has demonstrated inconsistent results, with a tendency to be elevated.[9,10,11] The consistency of studies of Glu in MDD makes it a preferable choice for a psychiatric control group. Future study designs should further elucidate the glutamatergic response to functional activation in schizophrenia

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