Evidence map›Paper›PMID 33398325›Full record

ArticleSchizophrenia bulletin2021

Changes in Brain Glutamate on Switching to Clozapine in Treatment-Resistant Schizophrenia.

Grant McQueen, Kyra-Verena Sendt, Amy Gillespie, Alessia Avila, John Lally, Kalliopi Vallianatou, Nynn Chang, Diogo Ferreira, Faith Borgan, Oliver D Howes and 6 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Schizophrenia bulletin, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed, 6 pooled it
4.2field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

45 citing papers in PubMed, 6 syntheses or guidelines pooled it, 65 citations in OpenAlex.

  1. Pooled it
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  14. Xanomeline-Trospium for the Treatment of Schizophrenia.Focus (American Psychiatric Publishing) · 2025
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors at 3 institutions in 3 countries.

Grant McQueenDepartment of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, De Crespigny Park, London, UK.
Kyra-Verena SendtDepartment of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, De Crespigny Park, London, UK.
Amy GillespieDepartment of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, De Crespigny Park, London, UK.
Alessia AvilaDepartment of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, De Crespigny Park, London, UK.
John LallyDepartment of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, De Crespigny Park, London, UK.
Kalliopi VallianatouDepartment of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, De Crespigny Park, London, UK.
Nynn ChangDepartment of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, De Crespigny Park, London, UK.
Diogo FerreiraHospital de Santa Maria, Centro Hospitalar Universitário de Lisboa Norte, Lisbon, Portugal.
Faith BorganDepartment of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, De Crespigny Park, London, UK.
Oliver D HowesDepartment of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, De Crespigny Park, London, UK.
Gareth J BarkerDepartment of Neuroimaging, Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology & Neuroimaging, King's College London, De Crespigny Park, London, UK.
David J LythgoeDepartment of Neuroimaging, Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology & Neuroimaging, King's College London, De Crespigny Park, London, UK.
James M StoneDepartment of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, De Crespigny Park, London, UK.
Philip McGuireDepartment of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, De Crespigny Park, London, UK.
James H MacCabeDepartment of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, De Crespigny Park, London, UK.
Alice EgertonDepartment of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, De Crespigny Park, London, UK.
King's College London · GBHospital de Santa Maria · PTRoyal College of Surgeons in Ireland · IE

Funding

Medical Research Council MC_U120097115Medical Research Council MR/L003988/1Medical Research Council MR/N027078/1
6 · The paper itself

Abstract

It has been suggested that the antipsychotic clozapine may modulate brain glutamate, and that this effect could contribute to its efficacy in treatment-resistant schizophrenia (TRS). The aim of this study was to examine the effects of clozapine on brain glutamate in TRS longitudinally. This study examined individuals with TRS before and 12 weeks after switching from a non-clozapine antipsychotic to treatment with clozapine as part of their normal clinical care. Proton magnetic resonance spectroscopy (1H-MRS) measured concentrations, corrected for voxel tissue content, of glutamate (Glucorr), and glutamate plus glutamine (Glxcorr) in the anterior cingulate cortex (ACC) and right caudate nucleus. Symptoms were monitored using the Positive and Negative Syndrome Scale (PANSS). Of 37 recruited patients (27 men, 39.30 years old, 84% clozapine naïve), 25 completed 1H-MRS at both timepoints. 12 weeks of clozapine was associated with a longitudinal reduction in Glucorr in the caudate (n = 23, F = 7.61 P = .01) but not in the ACC (n = 24, F = 0.02, P = .59). Percentage reduction in caudate Glucorr was positively correlated with percentage improvement in symptoms (total PANSS score, n = 23, r = .42, P = .04). These findings indicate that reductions in glutamate in the caudate nucleus may contribute to symptomatic improvement during the first months of clozapine treatment.

Indexed as

Caudate NucleusGlutamic AcidGyrus CinguliOutcome Assessment, Health CareSchizophreniaAdultAntipsychotic AgentsClozapineFemaleGlutamineHumansLongitudinal StudiesMaleMiddle AgedProton Magnetic Resonance SpectroscopyAntipsychotic AgentsClozapineGlutamic AcidGlutamine1H-MRSanterior cingulate cortexantipsychoticcaudatemagnetic resonance spectroscopypsychosis

Identifiers

PMID33398325
PMCPMC8084451
OpenAlexW3093846541

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.