Bill Deakin
Defining the disturbance in cortical glutamate and GABA function in psychosis and its origins and consequences
Deakin, Bill; Liddle, Elizabeth; Rathnaiah, Mohanbabu; Gregory, Cathy; Katshu, Mohammad; Wiliams, Gemma; Conen, Silke; Smallman, Richard; Koelewijn, Loes C.; Anton, Adriana; Kumar, Jyothika; Gasgoyne, Lauren E.; Chen, Chen; Nikkheslat, Naghmeh; Evans, John; Lanz, Bernard; Walters, James; Talbot, Peter; Palaniyappan, Lena; Singh, Krish D.; Morris, Peter; Williams, Steven R.; Liddle, Peter F.
Authors
ELIZABETH LIDDLE ELIZABETH.LIDDLE@NOTTINGHAM.AC.UK
Associate Professor
Mohanbabu Rathnaiah
Cathy Gregory
MOHAMMAD ZIA UL HAQ KATSHU MOHAMMAD.KATSHU@NOTTINGHAM.AC.UK
Clinical Associate Professor
Gemma Wiliams
Silke Conen
Richard Smallman
Loes C. Koelewijn
Adriana Anton
Jyothika Kumar
Lauren E. Gasgoyne
Chen Chen
Naghmeh Nikkheslat
John Evans
Bernard Lanz
James Walters
Peter Talbot
Lena Palaniyappan
Krish D. Singh
Peter Morris
Steven R. Williams
Peter F. Liddle
Abstract
It is widely thought that the onset of psychotic symptoms in schizophrenia may arise from an early neurotoxic phase, possibly related to oxidative stress or inflammation, and a late residual damage phase associated with persistent negative symptoms. We tested this hypothesis in a 3-centre study using magnetic resonance spectroscopy (MRS) to determine whether abnormalities in glutamate, glutamine and GABA content in anterior cingulate cortex (ACC) differed between people with minimally treated ‘Recent’ onset schizophrenia and an ‘Established’ group with > 10 years of treatment. We tested whether neurochemical abnormalities were i) mediated by raised circulating inflammatory cytokine concentrations, c-reactive protein (CRP) and interleukin-6 (IL-6), or depletion of glutathione and ii) associated with ratings of positive and negative symptoms. Relative to age-matched controls, the Established group showed significantly greater reduction in ACC glutamate than the Recent group, which did not differ from controls. This effect was not attributable to antipsychotic drug exposure. Patient ACC glutathione was negatively correlated with age. IL-6 was increased in both clinical groups, while increases in CRP were greater in the Established than Recent group. Elevated CRP was entirely accounted for by greater antipsychotic drug exposure and BMI, while residual elevation in IL-6 in the Established group did not account for their lower ACC glutamate. GABA was reduced relative to controls across ACC and occipital voxels. This reduction was not associated with drug treatment, BMI or cytokine levels. Only ACC GABA content correlated significantly with symptoms, lower content with greater positive and negative symptoms across both groups.
Citation
Deakin, B., Liddle, E., Rathnaiah, M., Gregory, C., Katshu, M., Wiliams, G., Conen, S., Smallman, R., Koelewijn, L. C., Anton, A., Kumar, J., Gasgoyne, L. E., Chen, C., Nikkheslat, N., Evans, J., Lanz, B., Walters, J., Talbot, P., Palaniyappan, L., Singh, K. D., …Liddle, P. F. Defining the disturbance in cortical glutamate and GABA function in psychosis and its origins and consequences
Working Paper Type | Working Paper |
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Deposit Date | Jul 3, 2024 |
Publicly Available Date | Jul 8, 2024 |
Public URL | https://nottingham-repository.worktribe.com/output/36579859 |
Publisher URL | https://www.medrxiv.org/content/10.1101/2024.06.26.24308831v1 |
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Defining the disturbance in cortical glutamate and GABA
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Publisher Licence URL
https://creativecommons.org/licenses/by-nc-nd/4.0/
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