Evidence map›Paper›PMID 25603859›Full record

ArticleThe international journal of neuropsychopharmacology2015

Glutamatergic neurometabolites in clozapine-responsive and -resistant schizophrenia.

Meghan Elizabeth Goldstein, Valerie Margaret Anderson, Avinesh Pillai, Robert R Kydd, Bruce R Russell

Erratum issuedOpen access · goldAbstract readComparative Study
PubMed Full text at PMC Publisher
In one paragraph

Article in The international journal of neuropsychopharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 54 papers, 12 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
54citing papers in PubMed, 12 pooled it
4.1field-weighted citation impact, top 6% 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

54 citing papers in PubMed, 12 syntheses or guidelines pooled it, 108 citations in OpenAlex.

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  19. Exploring causal mechanisms of psychosis risk.Neuroscience and biobehavioral reviews · 2024
    Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

5 authors at 3 institutions in 2 countries.

Meghan Elizabeth GoldsteinDepartment of Psychiatry, University of California, San Diego, CA (Dr Goldstein); School of Pharmacy and Centre for Brain Research, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand (Drs Goldstein, Anderson, and Russell and Mr Pillai); Centre for Brain Research and Department of Psychological Medicine, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand (Dr Kydd).
Valerie Margaret AndersonDepartment of Psychiatry, University of California, San Diego, CA (Dr Goldstein); School of Pharmacy and Centre for Brain Research, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand (Drs Goldstein, Anderson, and Russell and Mr Pillai); Centre for Brain Research and Department of Psychological Medicine, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand (Dr Kydd).
Avinesh PillaiDepartment of Psychiatry, University of California, San Diego, CA (Dr Goldstein); School of Pharmacy and Centre for Brain Research, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand (Drs Goldstein, Anderson, and Russell and Mr Pillai); Centre for Brain Research and Department of Psychological Medicine, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand (Dr Kydd).
Robert R KyddDepartment of Psychiatry, University of California, San Diego, CA (Dr Goldstein); School of Pharmacy and Centre for Brain Research, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand (Drs Goldstein, Anderson, and Russell and Mr Pillai); Centre for Brain Research and Department of Psychological Medicine, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand (Dr Kydd).
Bruce R RussellDepartment of Psychiatry, University of California, San Diego, CA (Dr Goldstein); School of Pharmacy and Centre for Brain Research, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand (Drs Goldstein, Anderson, and Russell and Mr Pillai); Centre for Brain Research and Department of Psychological Medicine, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand (Dr Kydd). b.russell@auckland.ac.nz.
Brain Research New Zealand · NZUniversity of Auckland · NZUniversity of California, San Diego · US

Funding

Inhibitory Deficits in Mania and Hyperdopaminiergic MiceR01MH071916 · NIMH · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GEYER, MARK A, PERRY, WILLIAM · 2004 to 2014
$4.2M
NIMH NIH HHS R01 MH071916
6 · The paper itself

Abstract

backgroundAccording to the current schizophrenia treatment guidelines, 3 levels of responsiveness to antipsychotic medication exist: those who respond to first-line antipsychotics, those with treatment-resistant schizophrenia who respond to clozapine, and those with clozapine-resistant or ultra-treatment resistant schizophrenia. Proton magnetic resonance spectroscopy studies indicate that antipsychotic medication decreases glutamate or total glutamate + glutamine in the brains of patients with schizophrenia and may represent a biomarker of treatment response; however, the 3 levels of treatment responsiveness have not been evaluated.

methodsProton magnetic resonance spectroscopy spectra were acquired at 3 Tesla from patients taking a second generation non-clozapine antipsychotic (first-line responders), patients with treatment-resistant schizophrenia taking clozapine, patients with ultra-treatment resistant schizophrenia taking a combination of antipsychotics, and healthy comparison subjects.

resultsGroup differences in cerebrospinal fluid-corrected total glutamate + glutamine levels scaled to creatine were detected in the dorsolateral prefrontal cortex [df(3,48); F = 3.07, P = .04, partial η(2) = 0.16] and the putamen [df(3,32); F = 2.93, P = .05, partial η(2) = 0.22]. The first-line responder group had higher dorsolateral prefrontal cortex total glutamate + glutamine levels scaled to creatine than those with ultra-treatment resistant schizophrenia [mean difference = 0.25, standard error = 0.09, P = .04, family-wise error-corrected]. Those with treatment-resistant schizophrenia had higher total glutamate + glutamine levels scaled to creatine in the putamen than the first-line responders (mean difference = 0.31, standard error = 0.12, P = .05, family-wise error-corrected) and those with ultra-treatment-resistant schizophrenia (mean difference = 0.39, standard error = 0.12, P = .02, family-wise error-corrected).

conclusionsTotal glutamate + glutamine levels scaled to creatine in the putamen may represent a marker of response to clozapine. Future studies should investigate glutamatergic anomalies prior to clozapine initiation and following successful treatment.

Indexed as

Drug ResistanceSchizophrenic PsychologyAdultAntipsychotic AgentsBiomarkersBrainCase-Control StudiesClozapineCreatineDrug Therapy, CombinationFemaleGlutamic AcidGlutamineHumansMagnetic Resonance ImagingMaleAntipsychotic AgentsBiomarkersClozapineCreatineGlutamic AcidGlutamineantipsychoticclozapineglutamatemagnetic resonance imagingschizophrenia

Identifiers

PMID25603859
PMCPMC4438552
OpenAlexW2161503386

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.