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Robert Bartha, BSc; Peter C. Williamson, MD; Dick J. Drost, PhD; Ashok Malla, MB; Tom J. Carr, MD; Len Cortese, MD; Gita Canaran, MA; R. Jane Rylett, PhD; Richard W. J. Neufeld, PhD

Arch Gen Psychiatry. 1997;54(10):959-965.

Abstract
Background
Positron emission tomographic and postmortem studies comparing schizophrenic patients with healthy control subjects have found medial prefrontal cortical and anterior cingulate abnormalities that suggest dysfunction in glutamatergic neurons. The glutamate used for nerve signal transduction is predominantly derived from glutamine. After signal transduction, glutamate released into the synapse is converted to glutamine in glial cells, transported back to the presynaptic neuron, and reconverted to glutamate for reuse. In this study, levels of glutamate and glutamine were examined by means of in vivo proton (¹H) magnetic resonance spectroscopy.

Methods
Localized in vivo¹H spectra were acquired from a 4.5-cm³ volume in the left medial prefrontal cortex encompassing portions of Brodmann areas 24, 32, and 9 in 10 never-treated schizophrenic subjects and 10 healthy controls of comparable age, sex, handedness, education, and parental education. From each spectrum, metabolite levels were estimated for glutamate and glutamine, as well as 10 other metabolites and 3 macromolecules, by means of a noninteractive computer program that combined modeled in vitro spectra of every metabolite to reconstruct each in vivo spectrum.

Results
A significant increase in glutamine level was found in the medial prefrontal cortex of the schizophrenic patients compared with controls. N-acetylaspartate and other measured metabolites and macromolecules were not significantly changed in schizophrenics.

Conclusion
Increased glutamine levels in the medial prefrontal region most likely reflect decreased glutamatergic activity in this region in never-treated schizophrenic patients compared with healthy controls.

Author Affiliations
From the Department of Nuclear Medicine and Magnetic Resonance, St Joseph's Health Centre (Mr Bartha and Drs Williamson, Drost, and Carr), and Departments of Psychiatry (Drs Williamson, Malla, and Cortese and Ms Canaran), Physiology (Dr Rylett), and Psychology (Dr Neufeld), University of Western Ontario.

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