Glutathione and glutamate in schizophrenia: a 7T MRS study
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 s...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
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Nature Publishing Group
2018
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| Online Access: | https://eprints.nottingham.ac.uk/52190/ |
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| author | Kumar, Jyothika Liddle, Elizabeth B. Fernandes, Carolina C. Palaniyappan, Lena Hall, Emma L. Robson, Siân E. Simmonite, M. Fiesal, Jan Katshu, Mohammad Z. Qureshi, Ayaz Skelton, Michael Christodoulou, Nikolaos G. Brookes, Matthew J. Morris, Peter G. Liddle, Peter F. |
| author_facet | Kumar, Jyothika Liddle, Elizabeth B. Fernandes, Carolina C. Palaniyappan, Lena Hall, Emma L. Robson, Siân E. Simmonite, M. Fiesal, Jan Katshu, Mohammad Z. Qureshi, Ayaz Skelton, Michael Christodoulou, Nikolaos G. Brookes, Matthew J. Morris, Peter G. Liddle, Peter F. |
| author_sort | Kumar, Jyothika |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | 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 postinflammatory response, and that this reduction would be most marked in patients with residual schizophrenia an early stage with positive psychotic symptoms has progressed to a late stage characterised 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 excito-toxicity during the acute phase of illness leads to reduced glutathione and glutamate in the residual phase of the illness. |
| first_indexed | 2025-11-14T20:23:27Z |
| format | Article |
| id | nottingham-52190 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T20:23:27Z |
| publishDate | 2018 |
| publisher | Nature Publishing Group |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-521902020-05-04T19:42:10Z https://eprints.nottingham.ac.uk/52190/ 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, M. Fiesal, Jan Katshu, Mohammad Z. Qureshi, Ayaz Skelton, Michael Christodoulou, Nikolaos G. Brookes, Matthew J. Morris, Peter G. Liddle, Peter F. 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 postinflammatory response, and that this reduction would be most marked in patients with residual schizophrenia an early stage with positive psychotic symptoms has progressed to a late stage characterised 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 excito-toxicity during the acute phase of illness leads to reduced glutathione and glutamate in the residual phase of the illness. Nature Publishing Group 2018-06-22 Article PeerReviewed Kumar, Jyothika, Liddle, Elizabeth B., Fernandes, Carolina C., Palaniyappan, Lena, Hall, Emma L., Robson, Siân E., Simmonite, M., Fiesal, Jan, Katshu, Mohammad Z., Qureshi, Ayaz, Skelton, Michael, Christodoulou, Nikolaos G., Brookes, Matthew J., Morris, Peter G. and Liddle, Peter F. (2018) Glutathione and glutamate in schizophrenia: a 7T MRS study. Molecular Psychiatry . ISSN 1476-5578 Glutathione; Glutamate; Glutamine; Schizophrenia; MRS; Anterior cingulate cortex; Insula; Residual https://www.nature.com/articles/s41380-018-0104-7 doi:10.1038/s41380-018-0104-7 doi:10.1038/s41380-018-0104-7 |
| spellingShingle | Glutathione; Glutamate; Glutamine; Schizophrenia; MRS; Anterior cingulate cortex; Insula; Residual Kumar, Jyothika Liddle, Elizabeth B. Fernandes, Carolina C. Palaniyappan, Lena Hall, Emma L. Robson, Siân E. Simmonite, M. 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 |
| title | Glutathione and glutamate in schizophrenia: a 7T MRS study |
| title_full | Glutathione and glutamate in schizophrenia: a 7T MRS study |
| title_fullStr | Glutathione and glutamate in schizophrenia: a 7T MRS study |
| title_full_unstemmed | Glutathione and glutamate in schizophrenia: a 7T MRS study |
| title_short | Glutathione and glutamate in schizophrenia: a 7T MRS study |
| title_sort | glutathione and glutamate in schizophrenia: a 7t mrs study |
| topic | Glutathione; Glutamate; Glutamine; Schizophrenia; MRS; Anterior cingulate cortex; Insula; Residual |
| url | https://eprints.nottingham.ac.uk/52190/ https://eprints.nottingham.ac.uk/52190/ https://eprints.nottingham.ac.uk/52190/ |