Anterior cingulate glutamate metabolites as a predictor of antipsychotic response in first episode psychosis: data from the STRATA collaboration

Elevated brain glutamate has been implicated in non-response to antipsychotic medication in schizophrenia. Biomarkers that can accurately predict antipsychotic non-response from the first episode of psychosis (FEP) could allow stratification of patients; for example, patients predicted not to respon...

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Published in:Neuropsychopharmacology (New York, N.Y.) N.Y.), 2023-02, Vol.48 (3), p.567-575
Main Authors: Egerton, Alice, Griffiths, Kira, Casetta, Cecila, Deakin, Bill, Drake, Richard, Howes, Oliver D, Kassoumeri, Laura, Khan, Sobia, Lankshear, Steve, Lees, Jane, Lewis, Shon, Mikulskaya, Elena, Millgate, Edward, Oloyede, Ebenezer, Pollard, Rebecca, Rich, Nathalie, Segev, Aviv, Sendt, Kyra-Verena, MacCabe, James H
Format: Article
Language:English
Subjects:
Antipsychotic Agents - pharmacology
Antipsychotic Agents - therapeutic use
Antipsychotics
Biomarkers
Clozapine
Cortex (cingulate)
Glutamic Acid - metabolism
Glutamine
Gyrus Cinguli - diagnostic imaging
Gyrus Cinguli - metabolism
Humans
Magnetic resonance spectroscopy
Mental disorders
Metabolites
Patients
Proton Magnetic Resonance Spectroscopy - methods
Psychosis
Psychotic Disorders - diagnostic imaging
Psychotic Disorders - drug therapy
Psychotic Disorders - metabolism
Psychotropic drugs
Remission
Schizophrenia
Schizophrenia - drug therapy
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Summary:Elevated brain glutamate has been implicated in non-response to antipsychotic medication in schizophrenia. Biomarkers that can accurately predict antipsychotic non-response from the first episode of psychosis (FEP) could allow stratification of patients; for example, patients predicted not to respond to standard antipsychotics could be fast-tracked to clozapine. Using proton magnetic resonance spectroscopy ( H-MRS), we examined the ability of glutamate and Glx (glutamate plus glutamine) in the anterior cingulate cortex (ACC) and caudate to predict response to antipsychotic treatment. A total of 89 minimally medicated patients with FEP not meeting symptomatic criteria for remission were recruited across two study sites. H-MRS and clinical data were acquired at baseline, 2 and 6 weeks. Response was defined as >20% reduction in Positive and Negative Syndrome Scale (PANSS) Total score from baseline to 6 weeks. In the ACC, baseline glutamate and Glx were higher in Non-Responders and significantly predicted response (P 
ISSN:0893-133X
1740-634X
DOI:10.1038/s41386-022-01508-w