Evidence map›Paper›PMID 35267893›Full record

ReviewNutrients2022

Emerging Evidence for the Widespread Role of Glutamatergic Dysfunction in Neuropsychiatric Diseases.

Thomas McGrath, Richard Baskerville, Marcelo Rogero, Linda Castell

Open access · goldAbstract readReview
In one paragraph

Review in Nutrients, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
53citing papers in PubMed, 4 pooled it
5.7field-weighted citation impact, top 2% 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

53 citing papers in PubMed, 4 syntheses or guidelines pooled it, 98 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Biodistribution, Radiation Dosimetry, and Kinetic Modeling of [Pharmaceuticals (Basel, Switzerland) · 2026
    Article
  6. Article
  7. Neuroprotective Potential ofBiomolecules · 2026
    Article
  8. Review
  9. Review
  10. Review
  11. Review
  12. Review
  13. Article
  14. Gut-brain axis in health and brain disease.Chinese medical journal · 2026
    Review
  15. Article
  16. Article
  17. Article
  18. Review
  19. Review
  20. Sigma-1-targeting multimodal compound HBK-15 reverses memory deficits and restores hippocampal plasticity under NMDA hypofunction.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026
    Article
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

4 authors at 3 institutions in 2 countries.

Thomas McGrathGreen Templeton College, University of Oxford, Oxford OX2 6HG, UK.
Richard BaskervilleFaculty of Health and Life Sciences, Oxford Brookes University, Oxford OX3 0BP, UK.
Marcelo RogeroSchool of Public Health, University of Sao Paulo, Sao Paulo 01246-904, Brazil.ORCID 0000-0003-0517-1645
Linda CastellGreen Templeton College, University of Oxford, Oxford OX2 6HG, UK.
University of Oxford · GBOxford Brookes University · GBUniversidade de São Paulo · BR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The monoamine model of depression has long formed the basis of drug development but fails to explain treatment resistance or associations with stress or inflammation. Recent animal research, clinical trials of ketamine (a glutamate receptor antagonist), neuroimaging research, and microbiome studies provide increasing evidence of glutamatergic dysfunction in depression and other disorders. Glutamatergic involvement across diverse neuropathologies including psychoses, neurodevelopmental, neurodegenerative conditions, and brain injury forms the rationale for this review. Glutamate is the brain's principal excitatory neurotransmitter (NT), a metabolic and synthesis substrate, and an immune mediator. These overlapping roles and multiple glutamate NT receptor types complicate research into glutamate neurotransmission. The glutamate microcircuit comprises excitatory glutamatergic neurons, astrocytes controlling synaptic space levels, through glutamate reuptake, and inhibitory GABA interneurons. Astroglia generate and respond to inflammatory mediators. Glutamatergic microcircuits also act at the brain/body interface via the microbiome, kynurenine pathway, and hypothalamus-pituitary-adrenal axis. Disruption of excitatory/inhibitory homeostasis causing neuro-excitotoxicity, with neuronal impairment, causes depression and cognition symptoms via limbic and prefrontal regions, respectively. Persistent dysfunction reduces neuronal plasticity and growth causing neuronal death and tissue atrophy in neurodegenerative diseases. A conceptual overview of brain glutamatergic activity and peripheral interfacing is presented, including the common mechanisms that diverse diseases share when glutamate homeostasis is disrupted.

Indexed as

Glutamic AcidSynaptic TransmissionAnimalsAstrocytesNeuronsNeurotransmitter AgentsGlutamic AcidNeurotransmitter Agentsdepressionexcitotoxicityglutamateglutamineinflammationneurodegenerationneuropsychiatric conditions

Identifiers

PMID35267893
PMCPMC8912368
OpenAlexW4213269251

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.