Article

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

Department of Psychiatry, University of New Mexico, Albuquerque, NM 87131-0001, USA.
Molecular Psychiatry (Impact Factor: 15.15). 11/2009; 15(6):629-36. DOI: 10.1038/mp.2009.121
Source: PubMed

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.

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    • "However , this could not be specifically attributed to declining ACC glutamate levels in the UHR compared with Control group , as the time by group interaction was above the threshold for statistical significance , and there was no evidence in UHR individuals that change in ACC glutamate levels were related to change in mental state . Nonetheless , lower levels of ACC glutamate in UHR subjects would consistent with the lower levels of frontal glutamate in schizophrenia reported by meta - analysis ( Marsman et al , 2011 ) , and in unaffected twins of patients with schizophrenia ( Lutkenhoff et al , 2010 ) , and partially consistent with studies in early psychosis that have reported elevated ACC glutamine ( Theberge et al , 2002 ; Theberge et al , 2007 ) , or elevated glutamine / glutamate ratio ( Bustillo et al , 2010 "
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    Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 06/2014; 39(12). DOI:10.1038/npp.2014.143 · 8.68 Impact Factor
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    • "To our knowledge, this is the first evidence that anterior cingulate glutamate levels differ between patients with schizophrenia in remission following antipsychotic treatment and patients who are still symptomatic. Higher levels of glutamate and Glx in the anterior cingulate cortex in symptomatic compared with remitted patients are consistent with reports of elevated anterior cingulate glutamate turnover in non-medicated or minimally treated patients, who generally have high levels of psychotic symptoms (Bustillo et al, 2010; Theberge et al, 2002). It is also in line with evidence that frontal glutamate is reduced in chronic patients with a long history of antipsychotic treatment and who are generally less symptomatic (Marsman et al, 2011; Tayoshi et al, 2009; Theberge et al, 2003). "
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    • "Of the five studies we found reporting measurements in the basal ganglia (Bertolino et al. 2001; Bustillo et al. 2001; Bustillo et al. 2008; Fannon et al. 2003; Heimberg et al. 1998) only Heimberg et al. reported any change, a decrease in Cho/ Cr. In the thalamus, three of five papers found no effects of medication (Bertolino et al. 2001; Bustillo et al. 2009; Heimberg et al. 1998). However, Szulc et al. (2007) reported decreased NAA/Cr in patients treated with typical antipsychotics compared with normal controls, but no differences in NAA/Cr between patients treated with typical or atypical antipsychotics. "
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