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Glutathione and glutamate in schizophrenia: a 7T MRS study

Kumar, Jyothika; Liddle, Elizabeth B.; Fernandes, Carolina C.; Palaniyappan, Lena; Hall, Emma L.; Robson, Siân E.; Simmonite, Molly; Fiesal, Jan; Katshu, Mohammad Z.; Qureshi, Ayaz; Skelton, Michael; Christodoulou, Nikolaos G.; Brookes, Matthew J.; Morris, Peter G.; Liddle, Peter F.

Glutathione and glutamate in schizophrenia: a 7T MRS study Thumbnail


Authors

Jyothika Kumar

Carolina C. Fernandes

Lena Palaniyappan

Emma L. Hall

Siân E. Robson

Molly Simmonite

Jan Fiesal

Ayaz Qureshi

Michael Skelton

Nikolaos G. Christodoulou

Peter G. Morris

Peter F. Liddle



Abstract

© 2018 The Author(s) In schizophrenia, abnormal neural metabolite concentrations may arise from cortical damage following neuroinflammatory processes implicated in acute episodes. Inflammation is associated with increased glutamate, whereas the antioxidant glutathione may protect against inflammation-induced oxidative stress. We hypothesized that patients with stable schizophrenia would exhibit a reduction in glutathione, glutamate, and/or glutamine in the cerebral cortex, consistent with a post-inflammatory response, and that this reduction would be most marked in patients with “residual schizophrenia”, in whom an early stage with positive psychotic symptoms has progressed to a late stage characterized by long-term negative symptoms and impairments. We recruited 28 patients with stable schizophrenia and 45 healthy participants matched for age, gender, and parental socio-economic status. We measured glutathione, glutamate and glutamine concentrations in the anterior cingulate cortex (ACC), left insula, and visual cortex using 7T proton magnetic resonance spectroscopy (MRS). Glutathione and glutamate were significantly correlated in all three voxels. Glutamine concentrations across the three voxels were significantly correlated with each other. Principal components analysis (PCA) produced three clear components: an ACC glutathione–glutamate component; an insula-visual glutathione–glutamate component; and a glutamine component. Patients with stable schizophrenia had significantly lower scores on the ACC glutathione–glutamate component, an effect almost entirely leveraged by the sub-group of patients with residual schizophrenia. All three metabolite concentration values in the ACC were significantly reduced in this group. These findings are consistent with the hypothesis that excitotoxicity during the acute phase of illness leads to reduced glutathione and glutamate in the residual phase of the illness.

Journal Article Type Article
Acceptance Date May 14, 2018
Online Publication Date Jun 22, 2018
Publication Date Jun 22, 2018
Deposit Date Jun 22, 2018
Publicly Available Date Jun 22, 2018
Journal Molecular Psychiatry
Print ISSN 1359-4184
Electronic ISSN 1476-5578
Publisher Nature Publishing Group
Peer Reviewed Peer Reviewed
Volume 25
Issue 4
Pages 873–882
DOI https://doi.org/10.1038/s41380-018-0104-7
Keywords Glutathione; Glutamate; Glutamine; Schizophrenia; MRS; Anterior cingulate cortex; Insula; Residual
Public URL https://nottingham-repository.worktribe.com/output/941475
Publisher URL https://www.nature.com/articles/s41380-018-0104-7

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