The association between peripheral inflammation, brain glutamate and antipsychotic response in Schizophrenia: Data from the STRATA collaboration

Fenn-Moltu, Sunniva, Deakin, Bill, Drake, Richard, Howes, Oliver D., Lawrie, Stephen M., Lewis, Shôn, Nikkheslat, Naghmeh, Walters, James T.R. ORCID: https://orcid.org/0000-0002-6980-4053, MacCabe, James H., Mondelli, Valeria and Egerton, Alice 2023. The association between peripheral inflammation, brain glutamate and antipsychotic response in Schizophrenia: Data from the STRATA collaboration. Brain, Behavior, and Immunity 111 , pp. 343-351. 10.1016/j.bbi.2023.05.005

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Abstract

Glutamate and increased inflammation have been separately implicated in the pathophysiology of schizophrenia and the extent of clinical response to antipsychotic treatment. Despite the mechanistic links between pro-inflammatory and glutamatergic pathways, the relationships between peripheral inflammatory markers and brain glutamate in schizophrenia have not yet been investigated. In this study, we tested the hypothesis that peripheral levels of pro-inflammatory cytokines would be positively associated with brain glutamate levels in schizophrenia. Secondary analyses determined whether this relationship differed according to antipsychotic treatment response. The sample consisted of 79 patients with schizophrenia, of whom 40 were rated as antipsychotic responders and 39 as antipsychotic non-responders. Brain glutamate levels were assessed in the anterior cingulate cortex (ACC) and caudate using proton magnetic resonance spectroscopy (1H-MRS) and blood samples were collected for cytokine assay on the same study visit (IL-6, IL-8, IL-10, TNF- α and IFN-γ). Across the whole patient sample, there was a positive relationship between interferon-gamma (IFN-γ) and caudate glutamate levels (r = 0.31, p = 0.02). In the antipsychotic non-responsive group only, there was a positive relationship between interleukin-8 (IL-8) and caudate glutamate (r = 0.46, p = 0.01). These findings provide evidence to link specific peripheral inflammatory markers and caudate glutamate in schizophrenia and may suggest that this relationship is most marked in patients who show a poor response to antipsychotic treatment.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Publisher:	Elsevier
ISSN:	0889-1591
Date of First Compliant Deposit:	7 March 2024
Date of Acceptance:	8 May 2023
Last Modified:	15 Mar 2024 12:27
URI:	https://orca.cardiff.ac.uk/id/eprint/166957

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