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 1 H-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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Conflict of interest G.J.B. received honoraria for teaching from General Electric Healthcare during the course of this study, and acts as a consultant for IXICO. A.E. has received research funding from the Roche and consultancy payment from Heptares Therapeutics. B.G. is the leader of a Lundbeck Foundation Center of Excellence for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS), which is partially financed by an independent grant from the Lundbeck Foundation based on international review and partially financed by the Mental Health Services in the Capital Region of Denmark, the University of Copenhagen and other foundations. P.M. has received consultancy payment for Sunovion and Takeda. R.P.I. has received honoraria as a speaker for Lundbeck. J.M.S. has received honoraria from Roche and Janssen and consultancy payment from Takeda. The remaining authors declare that they have no conflict of interest.
Acknowledgements This work was funded by a grant from the European Commission within the 7th Program (HEALTH-F2-2010-242114). We would like to thank the other OPTiMiSE investigators for their on-going support during the study. A.E. received additional support from the Brain and Behaviour Research Foundation (YIA 2012–18777). Research at the London site was supported by the Department of Health via the National Institute for Health Research (NIHR) Specialist Biomedical Research Center for Mental Health award to South London and Maudsley NHS Foundation Trust (SLaM) and the Institute of Psychiatry at King’s College London, London. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health.
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