Evidence map›Paper›PMID 26683625›Full record

ArticleSchizophrenia bulletin2016

Treatment-Resistant Schizophrenia Patients Show Elevated Anterior Cingulate Cortex Glutamate Compared to Treatment-Responsive.

Elias Mouchlianitis, Michael A P Bloomfield, Vincent Law, Katherine Beck, Sudhakar Selvaraj, Naresh Rasquinha, Adam Waldman, Federico E Turkheimer, Alice Egerton, James Stone and 1 more

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

Article in Schizophrenia bulletin, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 133 papers, 12 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
133citing papers in PubMed, 12 pooled it
11.9field-weighted citation impact, top 1% 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

133 citing papers in PubMed, 12 syntheses or guidelines pooled it, 224 citations in OpenAlex.

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  13. Does a monoclonal antibody targeting immune cells affect glutamatergic level in schizophrenia? A multimodal PET/MRS brain imaging study.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026
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73 more citing papers are in PubMed but not listed here.

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

11 authors at 4 institutions in 1 country.

Elias MouchlianitisMedical Research Council Clinical Sciences Centre, Psychiatric Imaging Group, Hammersmith Hospital, London, UK; Institute of Psychiatry Psychology and Neuroscience, Department of Psychosis Studies, King's College London, UK; elias.mouchlianitis@kcl.ac.uk.
Michael A P BloomfieldMedical Research Council Clinical Sciences Centre, Psychiatric Imaging Group, Hammersmith Hospital, London, UK; University College London, Division of Psychiatry, London, UK;
Vincent LawMedical Research Council Clinical Sciences Centre, Psychiatric Imaging Group, Hammersmith Hospital, London, UK;
Katherine BeckInstitute of Psychiatry Psychology and Neuroscience, Department of Psychosis Studies, King's College London, UK;
Sudhakar SelvarajDepartment of Psychiatry and Behavioral Sciences, University of Texas, Houston, TX;
Naresh RasquinhaPartnerships in Care, Mental Health Division, London, UK;
Adam WaldmanDivision of Brain Sciences, Imperial College London, Hammersmith Hospital, London, UK.
Federico E TurkheimerInstitute of Psychiatry Psychology and Neuroscience, Department of Psychosis Studies, King's College London, UK;
Alice EgertonInstitute of Psychiatry Psychology and Neuroscience, Department of Psychosis Studies, King's College London, UK;
James StoneMedical Research Council Clinical Sciences Centre, Psychiatric Imaging Group, Hammersmith Hospital, London, UK; Institute of Psychiatry Psychology and Neuroscience, Department of Psychosis Studies, King's College London, UK;
Oliver D HowesMedical Research Council Clinical Sciences Centre, Psychiatric Imaging Group, Hammersmith Hospital, London, UK; Institute of Psychiatry Psychology and Neuroscience, Department of Psychosis Studies, King's College London, UK;
Hammersmith Hospital · GBKing's College London · GBMedical Research Council · GBUniversity College London · GB

Funding

Medical Research Council G0700995Medical Research Council G1100809Medical Research Council MC-A656-5QD30Medical Research Council MC_U120097115Medical Research Council MR/L003988/1
6 · The paper itself

Abstract

introductionResistance to antipsychotic treatment is a significant clinical problem in patients with schizophrenia with approximately 1 in 3 showing limited or no response to repeated treatments with antipsychotic medication. The neurobiological basis for treatment resistance is unknown but recent evidence implicates glutamatergic function in the anterior cingulate cortex. We examined glutamate levels of chronically ill treatment-resistant patients directly compared to treatment-responsive patients.

methodsWe acquired proton magnetic resonance spectroscopy (1H-MRS) at 3 Tesla from 21 treatment-resistant and 20 treatment-responsive patients. All participants had a DSM-IV diagnosis of schizophrenia. Treatment-resistant patients were classified using the modified Kane criteria. The groups were matched for age, sex, smoking status, and illness duration.

resultsGlutamate to creatine ratio levels were higher in treatment-resistant patients (Mean [SD] = 1.57 [0.24]) than in treatment-responsive patients (Mean[SD] = 1.38 [0.23]), (T[35] = 2.34, P = .025, 2-tailed), with a large effect size of d = 0.76. A model assuming 2 populations showed a 25% improvement in the fit of the Akaike weights (0.55) over a model assuming 1 population (0.44), producing group values almost identical to actual group means. DISCUSSION: Increased anterior cingulate glutamate level is associated with treatment-resistant schizophrenia. This appears to be a stable neurobiological trait of treatment-resistant patients. We discuss possible explanations for glutamatergic dysfunction playing a significant role in resistance to conventional antipsychotic treatments, which are all dopamine-2 receptor blockers. Our findings suggest that glutamatergic treatments may be particularly effective in resistant patients and that 1H-MRS glutamate indices can potentially have clinical use.

Indexed as

AdultAntipsychotic AgentsChronic DiseaseDrug ResistanceFemaleGlutamic AcidGyrus CinguliHumansMaleMiddle AgedProton Magnetic Resonance SpectroscopySchizophreniaAntipsychotic AgentsGlutamic Acid1H-MRSantipsychoticsglutamateimaging and schizophrenianeurochemistryNMDApsychosistreatment- resistance

Identifiers

PMID26683625
PMCPMC4838083
OpenAlexW2217483770

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.