Evidence map›Paper›PMID 36806762›Full record

SynthesisMolecular psychiatry2023

Variability and magnitude of brain glutamate levels in schizophrenia: a meta and mega-analysis.

Kate Merritt, Robert A McCutcheon, André Aleman, Sarah Ashley, Katherine Beck, Wolfgang Block, Oswald J N Bloemen, Faith Borgan, Christiana Boules, Juan R Bustillo and 66 more

Open access · hybridAbstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Molecular psychiatry, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
52citing papers in PubMed, 5 pooled it
10.7field-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

52 citing papers in PubMed, 5 syntheses or guidelines pooled it, 72 citations in OpenAlex.

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  6. 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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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

76 authors at 20 institutions in 12 countries.

Kate Merritt *Division of Psychiatry, UCL, Institute of Mental Health, London, UK. K.merritt@ucl.ac.uk.ORCID 0000-0002-5716-4941
Robert A McCutcheon *Dept of Psychiatry, Warneford Hospital, University of Oxford, Oxford, UK.ORCID 0000-0003-1102-2566
André AlemanCenter for Brain Disorder and Cognitive Science, Shenzhen University, Shenzhen, China.
Sarah AshleyDivision of Psychiatry, UCL, Institute of Mental Health, London, UK.
Katherine BeckPsychosis Studies Department, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.ORCID 0000-0003-2769-8237
Wolfgang BlockDepartment of Diagnostic and Interventional Radiology, University Hospital Bonn, Bonn, Germany.
Oswald J N BloemenDepartment of Psychiatry and Neuropsychology, Maastricht University, Maastricht, the Netherlands.
Faith BorganPsychosis Studies Department, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.ORCID 0000-0002-5017-5226
Christiana BoulesPsychosis Studies Department, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Juan R BustilloDepartment of Psychiatry and Behavioral Sciences, Center for Psychiatric Research, University of New Mexico School of Medicine, Albuquerque, NM, USA.ORCID 0000-0001-8730-8152
Aristides A CapizzanoDepartment of Radiology, Division of Neuroradiology, University of Michigan, 1500 E Medical Center Dr, Ann Arbor, MI, 48109, USA.ORCID 0000-0003-1950-8499
Jennifer M CoughlinDepartment of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.ORCID 0000-0002-2514-9640
Anthony DavidDivision of Psychiatry, UCL, Institute of Mental Health, London, UK.
Camilo de la Fuente-SandovalLaboratory of Experimental Psychiatry, Instituto Nacional de Neurología y Neurocirugía, Mexico City, Mexico.ORCID 0000-0003-0773-1642
Arsime DemjahaPsychosis Studies Department, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Kara DempsterDepartment of Psychiatry, Dalhousie University, Halifax, NS, Canada.
Kim Q DoCenter for Psychiatric Neuroscience (CNP), Department of Psychiatry, Lausanne University Hospital-CHUV, Prilly-Lausanne, Switzerland.ORCID 0000-0003-1968-1646
Fei DuPsychotic Disorders Division, McLean Hospital, Harvard Medical School, Belmont, MA, USA.ORCID 0000-0002-9549-4255
Peter FalkaiDepartment of Psychiatry, University Hospital, LMU Munich, Nussbaumstrasse 7, 80336, Munich, Germany.
Beata Galińska-SkokDepartment of Psychiatry, Medical University of Bialystok, Bialystok, Poland.ORCID 0000-0002-9325-8304
Jürgen GallinatDepartment of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany.
Charles GasparovicMind Research Network, Albuquerque, NM, USA.
Cedric E GinestetDepartment of Biostatistics and Health Informatics (S2.06), Institute of Psychiatry, Psychology and Neuroscience King's College London, London, UK.
Naoki GotoDepartment of Psychiatry, Kokura Gamo Hospital, Kitakyushu, Fukuoka, 8020978, Japan.
Ariel Graff-GuerreroMultimodal Neuroimaging Schizophrenia Group, Research Imaging Centre, Geriatric Mental Health Program at Centre for Addiction and Mental Health, and Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
Beng-Choon HoDepartment of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA, USA.ORCID 0000-0003-3976-1555
Oliver HowesPsychosis Studies Department, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Sameer JauharPsychosis Studies Department, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.ORCID 0000-0002-3878-3659
Peter JeonDepartment of Medical Biophysics, University of Western Ontario, London, ON, Canada.
Tadafumi KatoDepartment of Psychiatry and Behavioral Science, Juntendo University Graduate School of Medicine, Tokyo, Japan.ORCID 0000-0001-7856-3952
Charles A KaufmannDepartment of Psychiatry, Columbia University, New York State Psychiatric Institute (NYSPI), New York, NY, USA.
Lawrence S KegelesColumbia University, Department of Psychiatry, New York State Psychiatric Institute (NYSPI), New York, NY, USA.
Matcheri S KeshavanHarvard Medical School, 75 Fenwood Rd., Boston, MA, 02115, USA.
Sang-Young KimPhilips Healthcare, Seoul, 0463, Republic of Korea.
Bridget KingPsychosis Studies Department, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.ORCID 0000-0001-5197-4567
Hiroshi KunugiNational Center of Neurology and Psychiatry, Kodaira, Tokyo, 187-0031, Japan.ORCID 0000-0002-7209-3790
J LaurielloJefferson Health-Sidney Kimmel Medical College, Philadelphia, PA, USA.
Pablo León-OrtizLaboratory of Experimental Psychiatry, Instituto Nacional de Neurología y Neurocirugía, Mexico City, Mexico.
Edith LiemburgRob Giel Research Center, Department of Psychiatry, University Medical Center Groningen, Groningen, the Netherlands.
Meghan E McilwainSchool of Pharmacy, University of Auckland, 85 Park Road, Grafton, Auckland, 1023, New Zealand.
Gemma ModinosPsychosis Studies Department, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.ORCID 0000-0002-7870-066X
Elias MouchlianitisPsychosis Studies Department, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Jun NakamuraDepartment of Psychiatry, University of Occupational and Environmental Health, Kitakyushu, Fukuoka, Japan.
Igor NenadicDepartment of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany.
Dost ÖngürPsychotic Disorders Division, McLean Hospital, Harvard Medical School, Belmont, MA, USA.
Miho OtaNational Center of Neurology and Psychiatry, Kodaira, Tokyo, 187-0031, Japan.
Lena PalaniyappanDepartment of Medical Biophysics, University of Western Ontario, London, ON, Canada.ORCID 0000-0003-1640-7182
Christos PantelisMelbourne Neuropsychiatry Centre, The University of Melbourne and Melbourne Health, Carlton, VIC, Australia.ORCID 0000-0002-9565-0238
Tulsi PatelDivision of Psychiatry, UCL, Institute of Mental Health, London, UK.
Eric PlitmanCerebral Imaging Centre, Douglas Mental Health University Institute, Montreal, QC, Canada.ORCID 0000-0002-7784-758X
Sotirios PosporelisPsychosis Studies Department, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.ORCID 0000-0001-8779-1068
Scot E PurdonNeuropsychology Department, Alberta Hospital Edmonton, Edmonton, AB, Canada.
Jürgen R ReichenbachMedical Physics Group, Institute for Diagnostic and Interventional Radiology (IDIR), Jena University Hospital, Jena, Germany.
Perry F RenshawDepartment of Psychiatry, University of Utah, Salt Lake City, UT, USA.ORCID 0000-0002-8888-4503
Francisco Reyes-MadrigalLaboratory of Experimental Psychiatry, Instituto Nacional de Neurología y Neurocirugía, Mexico City, Mexico.ORCID 0000-0003-0772-4119
Bruce R RussellSchool of Pharmacy, University of Otago, Dunedin, New Zealand.
Akira SawaDepartments of Psychiatry, Neuroscience, Mental Health, Biomedical Engineering, and Genetic Medicine, Johns Hopkins University, Baltimore, MD, USA.ORCID 0000-0003-1401-3008
Martin SchaeferDepartment of Psychiatry, Psychotherapy, Psychosomatics and Addiction Medicine, Kliniken Essen-Mitte, Essen, Germany.
Dikoma C ShunguDepartment of Radiology, Weill Cornell Medical College, New York City, NY, USA.ORCID 0000-0001-9452-2245
Stefan SmesnyDepartment of Psychiatry and Psychotherapy, Jena University Hospital, Jena, Germany.
Jeffrey A StanleyBrain Imaging Research Division, Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI, USA.
James StoneDepartment of Neuroimaging, Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology & Neuroscience, De Crespigny Park, London, SE5 8AF, UK.
Agata SzulcDepartment of Psychiatry, Medical University of Warsaw, Warsaw, Poland.
Reggie TaylorDepartment of Medical Biophysics, University of Western Ontario, London, ON, Canada.
Katharine N ThakkarDepartment of Psychology, Michigan State University, East Lansing, MI, USA.ORCID 0000-0002-0026-2030
Jean ThébergeDepartment of Medical Biophysics, University of Western Ontario, London, ON, Canada.ORCID 0000-0001-7578-4469
Philip G TibboDepartment of Psychiatry, Dalhousie University, Halifax, NS, Canada.
Thérèse van AmelsvoortDepartment of Psychiatry and Neuropsychology, Maastricht University, Maastricht, the Netherlands.
Jerzy WaleckiPostgraduate Medical School, Warsaw, Poland.
Peter C WilliamsonLawson Health Research Institute, London, ON, Canada.
Stephen J WoodOrygen, Melbourne, VIC, Australia.
Lijing XinAnimal Imaging and Technology Core (AIT), Center for Biomedical Imaging (CIBM), Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
Hidenori YamasueDepartment of Psychiatry, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Philip McGuirePsychosis Studies Department, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.ORCID 0000-0003-4381-0532
Alice EgertonPsychosis Studies Department, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.ORCID 0000-0003-2939-064X
1H-MRS in Schizophrenia Investigators
King's College London · GBWestern University · CAInstituto Nacional de Neurología y Neurocirugía · MXHarvard University · USInstitute of Mental Health · GBMaastricht University · NLDalhousie University · CAJena University Hospital · DEJohns Hopkins University · USNational Center of Neurology and Psychiatry · JPNew York Psychoanalytic Society and Institute · USThe University of Melbourne · AUUniversität Hamburg · DEUniversity Medical Center Groningen · NLBrighton and Sussex Medical School · GBCentre d'Imagerie BioMedicale · CHCentre for Addiction and Mental Health · CACornell University · USDouglas Mental Health University Institute · CAHamamatsu University School of Medicine · JP

Funding

Biomarkers of Conversion Risk and Treatment Response in Early-Stage SchizophreniaR01MH110270 · NIMH · WEILL MEDICAL COLL OF CORNELL UNIV · PI GIRGIS, RAGY RAMSIS, KEGELES, LAWRENCE S · 2017 to 2021
$3.7M
Medical Research Council MR/L003988/1Medical Research Council MR/S003436/1NIMH NIH HHS R01 MH110270Wellcome Trust
6 · The paper itself

Abstract

Glutamatergic dysfunction is implicated in schizophrenia pathoaetiology, but this may vary in extent between patients. It is unclear whether inter-individual variability in glutamate is greater in schizophrenia than the general population. We conducted meta-analyses to assess (1) variability of glutamate measures in patients relative to controls (log coefficient of variation ratio: CVR); (2) standardised mean differences (SMD) using Hedges g; (3) modal distribution of individual-level glutamate data (Hartigan's unimodality dip test). MEDLINE and EMBASE databases were searched from inception to September 2022 for proton magnetic resonance spectroscopy (1H-MRS) studies reporting glutamate, glutamine or Glx in schizophrenia. 123 studies reporting on 8256 patients and 7532 controls were included. Compared with controls, patients demonstrated greater variability in glutamatergic metabolites in the medial frontal cortex (MFC, glutamate: CVR = 0.15, p < 0.001; glutamine: CVR = 0.15, p = 0.003; Glx: CVR = 0.11, p = 0.002), dorsolateral prefrontal cortex (glutamine: CVR = 0.14, p = 0.05; Glx: CVR = 0.25, p < 0.001) and thalamus (glutamate: CVR = 0.16, p = 0.008; Glx: CVR = 0.19, p = 0.008). Studies in younger, more symptomatic patients were associated with greater variability in the basal ganglia (BG glutamate with age: z = -0.03, p = 0.003, symptoms: z = 0.007, p = 0.02) and temporal lobe (glutamate with age: z = -0.03, p = 0.02), while studies with older, more symptomatic patients associated with greater variability in MFC (glutamate with age: z = 0.01, p = 0.02, glutamine with symptoms: z = 0.01, p = 0.02). For individual patient data, most studies showed a unimodal distribution of glutamatergic metabolites. Meta-analysis of mean differences found lower MFC glutamate (g = -0.15, p = 0.03), higher thalamic glutamine (g = 0.53, p < 0.001) and higher BG Glx in patients relative to controls (g = 0.28, p < 0.001). Proportion of males was negatively associated with MFC glutamate (z = -0.02, p < 0.001) and frontal white matter Glx (z = -0.03, p = 0.02) in patients relative to controls. Patient PANSS total score was positively associated with glutamate SMD in BG (z = 0.01, p = 0.01) and temporal lobe (z = 0.05, p = 0.008). Further research into the mechanisms underlying greater glutamatergic metabolite variability in schizophrenia and their clinical consequences may inform the identification of patient subgroups for future treatment strategies.

Indexed as

Glutamic AcidSchizophreniaBrainGlutamineHumansMaleProton Magnetic Resonance SpectroscopyGlutamic AcidGlutamine

Identifiers

PMID36806762
PMCPMC10575771
OpenAlexW4321215188

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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.