Evidence map›Paper›PMID 23070074›Full record

ArticleMolecular psychiatry2013

Molecular evidence of N-methyl-D-aspartate receptor hypofunction in schizophrenia.

C S Weickert, S J Fung, V S Catts, P R Schofield, K M Allen, L T Moore, K A Newell, D Pellen, X-F Huang, S V Catts and 1 more

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

Article in Molecular psychiatry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 141 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
141citing papers in PubMed, 4 pooled it
8.0field-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

141 citing papers in PubMed, 4 syntheses or guidelines pooled it, 237 citations in OpenAlex.

  1. Pooled it
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  8. Article
  9. NMDA receptor ablation in medial prefrontal cortex disrupts value updating and reward history integration.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026
    Article
  10. Review
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  12. Article
  13. Altered Molecular Composition of a Specific Subset of Prefrontal Cortical Excitatory Synapses in Schizophrenia.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025
    Article
  14. Review
  15. Early postnatal NMDA receptor ablation in cortical interneurons impairs affective state discrimination and social functioning.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025
    Article
  16. Frontiers in cellular and infection microbiology · 2025
    Review
  17. Article
  18. Article
  19. Review
  20. Review

81 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 5 institutions in 1 country.

C S Weickert1] Schizophrenia Research Institute, Sydney, NSW, Australia [2] Neuroscience Research Australia, Sydney, NSW, Australia [3] School of Psychiatry, University of New South Wales, Sydney, NSW, Australia.
S J Fung
V S Catts
P R Schofield
K M Allen
L T Moore
K A Newell
D Pellen
X-F Huang
S V Catts
T W Weickert
Neuroscience Research Australia · AUUNSW Sydney · AUSchizophrenia Research Institute · AUUniversity of Queensland · AUUniversity of Wollongong · AU

Funding

Brain Tissue Resource Centre for Alcohol ResearchR28AA012725 · NIAAA · UNIVERSITY OF SYDNEY · PI Greg Trevor Sutherland · 2012 to 2026
$7.0M
NIAAA NIH HHS R28 AA012725
6 · The paper itself

Abstract

Blockade of N-methyl-D-aspartate receptors (NMDARs) produces behavior in healthy people that is similar to the psychotic symptoms and cognitive deficits of schizophrenia and can exacerbate symptoms in people with schizophrenia. However, an endogenous brain disruption of NMDARs has not been clearly established in schizophrenia. We measured mRNA transcripts for five NMDAR subunit mRNAs and protein for the NR1 subunit in the dorsolateral prefrontal cortex (DLPFC) of schizophrenia and control (n=74) brains. Five NMDAR single-nucleotide polymorphisms (SNPs) previously associated with schizophrenia were tested for association with NMDAR mRNAs in postmortem brain and for association with cognitive ability in an antemortem cohort of 101 healthy controls and 48 people with schizophrenia. The NR1 subunit (mRNA and protein) and NR2C mRNA were decreased in postmortem brain from people with schizophrenia (P=0.004, P=0.01 and P=0.01, respectively). In the antemortem cohort, the minor allele of NR2B rs1805502 (T5988C) was associated with significantly lower reasoning ability in schizophrenia. In the postmortem brain, the NR2B rs1805502 (T5988C) C allele was associated with reduced expression of NR1 mRNA and protein in schizophrenia. Reduction in NR1 and NR2C in the DLPFC of people with schizophrenia may lead to altered NMDAR stoichiometry and provides compelling evidence for an endogenous NMDAR deficit in schizophrenia. Genetic variation in the NR2B gene predicts reduced levels of the obligatory NR1 subunit, suggesting a novel mechanism by which the NR2B SNP may negatively influence other NMDAR subunit expression and reasoning ability in schizophrenia.

Indexed as

CognitionSchizophrenic PsychologyAdultAllelesCase-Control StudiesFemaleGenetic Predisposition to DiseaseGenotypeHumansMaleMiddle AgedPolymorphism, Single NucleotidePrefrontal CortexProtein SubunitsReceptors, N-Methyl-D-AspartateSchizophreniaNR1 NMDA receptorProtein SubunitsReceptors, N-Methyl-D-Aspartate

Identifiers

PMID23070074
PMCPMC3807670
OpenAlexW2053938654

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.