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Response to initial antipsychotic treatment in first episode psychosis is related to anterior cingulate glutamate levels: A multicentre 1H-MRS study (OPTiMiSE)

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Alice Egerton, Brian V. Broberg, Neeltje E. M. van Haren, Kate Sky Merritt, Gareth John Barker, David John Lythgoe, Rocio Perez-Iglesias, Lone Baandrup, Signe During, Kyra-Verena Sendt, James Michael Stone, Egill Rostrup, Iris E. C. Sommer, Birte Glenthøj, René S. Kahn, Paola Dazzan, Philip McGuire

Original languageEnglish
Pages (from-to)2145–2155
JournalMolecular Psychiatry
Early online date7 Jun 2018
Accepted/In press4 Apr 2018
E-pub ahead of print7 Jun 2018
PublishedNov 2018


King's Authors


Conventional antipsychotic medication is ineffective in around a third of patients with schizophrenia, and the nature of the therapeutic response is unpredictable. We investigated whether response to antipsychotics is related to brain glutamate levels prior to treatment. Proton magnetic resonance spectroscopy was used to measure glutamate levels (Glu/Cr) in the anterior cingulate cortex (ACC) and in the thalamus in antipsychotic-naive or minimally medicated patients with first episode psychosis (FEP, n = 71) and healthy volunteers (n = 60), at three sites. Following scanning, patients were treated with amisulpride for 4 weeks (n = 65), then 1H-MRS was repeated (n = 46). Remission status was defined in terms of Positive and Negative Syndrome Scale for Schizophrenia (PANSS) scores. Higher levels of Glu/Cr in the ACC were associated with more severe symptoms at presentation and a lower likelihood of being in remission at 4 weeks (P < 0.05). There were longitudinal reductions in Glu/Cr in both the ACC and thalamus over the treatment period (P < 0.05), but these changes were not associated with the therapeutic response. There were no differences in baseline Glu/Cr between patients and controls. These results extend previous evidence linking higher levels of ACC glutamate with a poor antipsychotic response by showing that the association is evident before the initiation of treatment.

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