TY - JOUR

T1 - Response to initial antipsychotic treatment in first episode psychosis is related to anterior cingulate glutamate levels

T2 - a multicentre 1H-MRS study (OPTiMiSE)

AU - Egerton, A.

AU - Broberg, B. V.

AU - Van Haren, N.

AU - Merritt, K.

AU - Barker, G. J.

AU - Lythgoe, D. J.

AU - Perez-Iglesias, R.

AU - Baandrup, L.

AU - Düring, S. W.

AU - Sendt, K. V.

AU - Stone, J. M.

AU - Rostrup, E.

AU - Sommer, I. E.

AU - Glenthøj, B.

AU - Kahn, R. S.

AU - Dazzan, P.

AU - McGuire, P.

PY - 2018

Y1 - 2018

N2 - 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.

AB - 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.

U2 - 10.1038/s41380-018-0082-9

DO - 10.1038/s41380-018-0082-9

M3 - Journal article

C2 - 29880882

AN - SCOPUS:85048109099

VL - 23

SP - 2145

EP - 2155

JO - Molecular Psychiatry

JF - Molecular Psychiatry

SN - 1359-4184

IS - 11

ER -