1H-MRS at 4 tesla in minimally treated early schizophrenia

Abstract

We investigated glutamate-related neuronal dysfunction in the anterior cingulate (AC) early in schizophrenia before and after antipsychotic treatment. A total of 14 minimally treated schizophrenia patients and 10 healthy subjects were studied with single-voxel proton magnetic resonance spectroscopy ((1)H-MRS) of the AC, frontal white matter and thalamus at 4 T. Concentrations of N-acetylaspartate (NAA), glutamate (Glu), glutamine (Gln) and Gln/Glu ratios were determined and corrected for the partial tissue volume. Patients were treated with antipsychotic medication following a specific algorithm and (1)H-MRS was repeated after 1, 6 and 12 months. There were group x region interactions for baseline NAA (P=0.074) and Gln/Glu (P=0.028): schizophrenia subjects had lower NAA (P=0.045) and higher Gln/Glu (P=0.006) in the AC before treatment. In addition, AC Gln/Glu was inversely related to AC NAA in the schizophrenia (P=0.0009) but not in the control group (P=0.92). Following antipsychotic treatment, there were no further changes in NAA, Gln/Glu or any of the other metabolites in any of the regions studied. We conclude that early in the illness, schizophrenia patients already show abnormalities in glutamatergic metabolism and reductions in NAA consistent with glutamate-related excitotoxicity.

Conflict of interest statement

Conflict of interest

The authors declare no conflict of interest.

Figures

Figure 1

Voxel placement in three regions of interest: the anterior cingulate, left frontal white matter and left thalamus. Representative spectra with the raw (in black) and fitted data (in red) are shown for each region. The color reproduction of the figure is available on the html full text version of the paper.

Figure 2

Neurometabolite levels (means ± s.d.) in the anterior cingulate in minimally treated early schizophrenia patients and healthy controls at baseline. For N-acetylaspartate (NAA), t(1, 20) = −2.16, *P = 0.045.

Figure 3

Glutamine–glutamate ratios (means ± s.d.) in the anterior cingulate in minimally treated early schizophrenia patients and healthy controls at baseline. For Gln/Glu, t(1, 20) = 3.15, *P = 0.006.

Figure 4

Inverse correlation between anterior cingulate N-acetylaspartate (NAA) and glutamine (Gln)/glutamate (Glu) ratio in schizophrenia at baseline, but not in healthy controls. Pearson’s r(14) = −0.78, P = 0.0009 in schizophrenia. Pearson’s r(8) = −0.044, P = 0.92 in control group.