7T Proton Magnetic Resonance Spectroscopy of Gamma-Aminobutyric Acid, Glutamate, and Glutamine Reveals Altered Concentrations in Patients With Schizophrenia and Healthy Siblings.

Abstract

BACKGROUND:

The N-methyl-D-aspartate receptor hypofunction model of schizophrenia predicts dysfunction in both glutamatergic and gamma-aminobutyric acidergic (GABAergic) transmission. We addressed this hypothesis by measuring GABA, glutamate, glutamine, and the sum of glutamine plus glutamate concentrations in vivo in patients with schizophrenia using proton magnetic resonance spectroscopy at 7T, which allows separation of metabolites that would otherwise overlap at lower field strengths. In addition, we investigated whether altered levels of GABA, glutamate, glutamine, and the sum of glutamine plus glutamate reflect genetic vulnerability to schizophrenia by including healthy first-degree relatives.

METHODS:

Proton magnetic resonance spectroscopy at 7T was performed in 21 patients with chronic schizophrenia who were taking medication, 23 healthy first-degree relatives of patients with schizophrenia, and 24 healthy nonrelatives. Glutamate, glutamine, and GABA were measured cortically and subcortically in bilateral basal ganglia and occipital cortex.

RESULTS:

Patients with schizophrenia had reduced cortical GABA compared with healthy relatives and the combined sample of healthy relatives and healthy nonrelatives, suggesting that altered GABAergic systems in schizophrenia are associated with either disease state or medication effects. Reduced cortical glutamine relative to healthy control subjects was observed in patients with schizophrenia and the combined sample of healthy relatives and patients with schizophrenia, suggesting that altered glutamatergic metabolite levels are associated with illness liability. No group differences were found in the basal ganglia.

CONCLUSIONS:

Taken together, these findings are consistent with alterations in GABAergic and glutamatergic systems in patients with schizophrenia and provide novel insights into these systems in healthy relatives.

• Authors: Katharine N Thakkar, Lara Rösler, Jannie P Wijnen, Vincent O Boer, Dennis W J Klomp, Wiepke Cahn, René S Kahn, Sebastiaan F W Neggers
• Journal: Biological psychiatry (Biol Psychiatry) Vol. 81 Issue 6 Pg. 525-535 (03 15 2017) ISSN: 1873-2402 [Electronic] United States
• PMID: 27316853 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Chemical References

• Glutamine
• Glutamic Acid
• gamma-Aminobutyric Acid

Topics

• Adult
• Brain (metabolism)
• Female
• Genetic Predisposition to Disease
• Glutamic Acid (metabolism)
• Glutamine (metabolism)
• Humans
• Male
• Proton Magnetic Resonance Spectroscopy
• Schizophrenia (metabolism)
• Siblings
• gamma-Aminobutyric Acid (metabolism)