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

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Molecular Psychiatry advance online publication 17 November 2009; doi: 10.1038/mp.2009.121

J R Bustillo^1,2, L M Rowland³, P Mullins⁴, R Jung^4,5,6, H Chen¹, C Qualls⁷, R Hammond¹, W M Brooks⁸ and J Lauriello¹

1. Department of Psychiatry, University of New Mexico, Albuquerque, NM, USA
2. Department of Neurosciences, University of New Mexico, Albuquerque, NM, USA
3. Maryland Psychiatric Research Center, University of Maryland, Baltimore, MD, USA
4. The Mental Illness and Neuroscience Discovery Institute, Albuquerque, NM, USA
5. Department of Psychology, University of New Mexico, Albuquerque, NM, USA
6. Department of Neurology, University of New Mexico, Albuquerque, NM, USA
7. Department of Mathematics & Statistics, University of New Mexico, Albuquerque, NM, USA
8. Hoglund Brain Imaging Center, Department of Neurology, University of Kansas Medical Center, Kansas City, KS, USA

Correspondence: JR Bustillo, Department of Psychiatry, University of New Mexico, 1101 Yale st NE, MSC09 5030, Albuquerque, NM 87131-0001, USA. E-mail: jbustillo@salud.unm.edu

Received 11 February 2009; Revised 28 September 2009; Accepted 5 October 2009; Published online 17 November 2009.

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 (¹H-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 ¹H-MRS was repeated after 1, 6 and 12 months. There were group 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.