Evidence map›Paper›PMID 25000913›Full record

ReviewSchizophrenia research2016

Redox dysregulation, neuroinflammation, and NMDA receptor hypofunction: A "central hub" in schizophrenia pathophysiology?

P Steullet, J H Cabungcal, A Monin, D Dwir, P O'Donnell, M Cuenod, K Q Do

Registry-linked trialAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Schizophrenia research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05142735 (Effects of N-acetylcysteine on Psychosis-like Symptoms and a Neurophysiological Biomarker of the Clinical High Risk for Schizophrenia), which is not on this map. Cited by 159 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
159citing papers in PubMed, 4 pooled it
–field-weighted citation impact
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.

NCT05142735 narecruitingnot on this mapstarted 2023, after this paper: background citation

Effects of N-acetylcysteine on Psychosis-like Symptoms and a Neurophysiological Biomarker of the Clinical High Risk for Schizophrenia

TypeinterventionalSponsorCentre for Addiction and Mental HealthRan2023 to 2026Enrolled90ConditionsProdromal SchizophreniaArmsN-Acetylcysteine, Placebo
3 · Its place in the literature

Who cites it

159 citing papers in PubMed, 4 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Trial
  6. Trial
  7. Trial
  8. Changes in Glutathione and Homocysteine Concentrations in Treatment-Resistant Depression After Electroconvulsive Therapy.Medical science monitor : international medical journal of experimental and clinical research · 2026
    Article
  9. Review
  10. Review
  11. Article
  12. Review
  13. Review
  14. Review
  15. Article
  16. Article
  17. Article
  18. Review
  19. Article
  20. Article

99 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

7 authors.

P SteulletCenter for Psychiatric Neuroscience, Department of Psychiatry, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Site de Cery, 1008 Prilly-Lausanne, Switzerland.
J H CabungcalCenter for Psychiatric Neuroscience, Department of Psychiatry, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Site de Cery, 1008 Prilly-Lausanne, Switzerland.
A MoninCenter for Psychiatric Neuroscience, Department of Psychiatry, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Site de Cery, 1008 Prilly-Lausanne, Switzerland.
D DwirCenter for Psychiatric Neuroscience, Department of Psychiatry, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Site de Cery, 1008 Prilly-Lausanne, Switzerland.
P O'DonnellNeuroscience Research Unit, Pfizer, Inc., 700 Main Street, Cambridge, MA 02139, USA.
M CuenodCenter for Psychiatric Neuroscience, Department of Psychiatry, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Site de Cery, 1008 Prilly-Lausanne, Switzerland.
K Q DoCenter for Psychiatric Neuroscience, Department of Psychiatry, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Site de Cery, 1008 Prilly-Lausanne, Switzerland. Electronic address: Kim.Do@chuv.ch.

Funding

ELECTROPHYSIOLOGY OF THE PREFRONTAL CORTEXR01MH057683 · NIMH · UNIVERSITY OF MARYLAND BALTIMORE · PI O'DONNELL, PATRICIO · 1997 to 2012
$3.2M
NIMH NIH HHS R01 MH057683
6 · The paper itself

Abstract

Accumulating evidence points to altered GABAergic parvalbumin-expressing interneurons and impaired myelin/axonal integrity in schizophrenia. Both findings could be due to abnormal neurodevelopmental trajectories, affecting local neuronal networks and long-range synchrony and leading to cognitive deficits. In this review, we present data from animal models demonstrating that redox dysregulation, neuroinflammation and/or NMDAR hypofunction (as observed in patients) impairs the normal development of both parvalbumin interneurons and oligodendrocytes. These observations suggest that a dysregulation of the redox, neuroimmune, and glutamatergic systems due to genetic and early-life environmental risk factors could contribute to the anomalies of parvalbumin interneurons and white matter in schizophrenia, ultimately impacting cognition, social competence, and affective behavior via abnormal function of micro- and macrocircuits. Moreover, we propose that the redox, neuroimmune, and glutamatergic systems form a "central hub" where an imbalance within any of these "hub" systems leads to similar anomalies of parvalbumin interneurons and oligodendrocytes due to the tight and reciprocal interactions that exist among these systems. A combination of vulnerabilities for a dysregulation within more than one of these systems may be particularly deleterious. For these reasons, molecules, such as N-acetylcysteine, that possess antioxidant and anti-inflammatory properties and can also regulate glutamatergic transmission are promising tools for prevention in ultra-high risk patients or for early intervention therapy during the first stages of the disease.

Indexed as

InflammationInterneuronsOligodendrogliaOxidation-ReductionParvalbuminsReceptors, N-Methyl-D-AspartateSchizophreniaHumansParvalbuminsReceptors, N-Methyl-D-AspartateDevelopmentMyelinationN-acetylcysteineOligodendrocytesOxidative stressParvalbumin interneurons

Identifiers

PMID25000913
PMCPMC4282982

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

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.