Cited by 113Tryptophan and brain disordersSchizophrenia research and treatmentNeuroinflammation and Neurodegeneration Mechanisms

Linking inflammation, aberrant glutamate-dopamine interaction, and post-synaptic changes: translational relevance for schizophrenia and antipsychotic treatment: a systematic review

Open access
de Bartolomeis, Andrea, Barone, Annarita, Vellucci, Licia, Mazza, Benedetta, Austin, Mark C., Iasevoli, Felice, Ciccarelli, Mariateresa·2022·Molecular Neurobiology

Abstract

Evidence from clinical, preclinical, and post-mortem studies supports the inflammatory/immune hypothesis of schizophrenia pathogenesis. Less evident is the link between the inflammatory background and two well-recognized functional and structural findings of schizophrenia pathophysiology: the dopamine-glutamate aberrant interaction and the alteration of dendritic spines architecture, both believed to be the "quantal" elements of cortical-subcortical dysfunctional network. In this systematic review, we tried to capture the major findings linking inflammation, aberrant glutamate-dopamine interaction, and post-synaptic changes under a direct and inverse translational perspective, a paramount picture that at present is lacking. The inflammatory effects on dopaminergic function appear to be bidirectional: the inflammation influences dopamine release, and dopamine acts as a regulator of discrete inflammatory processes involved in schizophrenia such as dysregulated interleukin and kynurenine pathways. Furthermore, the link between inflammation and glutamate is strongly supported by clinical studies aimed at exploring overactive microglia in schizophrenia patients and maternal immune activation models, indicating impaired glutamate regulation and reduced N-methyl-D-aspartate receptor (NMDAR) function. In addition, an inflammatory/immune-induced alteration of post-synaptic density scaffold proteins, crucial for downstream NMDAR signaling and synaptic efficacy, has been demonstrated. According to these findings, a significant increase in plasma inflammatory markers has been found in schizophrenia patients compared to healthy controls, associated with reduced cortical integrity and functional connectivity, relevant to the cognitive deficit of schizophrenia. Finally, the link between altered inflammatory/immune responses raises relevant questions regarding potential new therapeutic strategies specifically for those forms of schizophrenia that are resistant to canonical antipsychotics or unresponsive to clozapine.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1007/s12035-022-02976-3

Cites

325 of 325 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 2

  1. [168]Li R Ma X Wang G Yang J Wang C Why sex differences in schizophrenia? J transl neuroscience 2016 1 1 37 42 PMC5688947 29152382
  2. [289]Müller N 2010 COX-2 inhibitors as antidepressants and antipsychotics: clinical evidence. Current opinion in investigational drugs (London, England: 2000) 11 (1):31–42 20047157

Cited by

Sorted by citations

Authors
de Bartolomeis, A., Barone, A., Vellucci, L., Mazza, B., Austin, M. C., Iasevoli, F., & Ciccarelli, M.
Affiliations
  • Federico II University Hospital (IT)
  • Idaho State University (US)
Venue
Molecular Neurobiology
Published
2022-08-13
Volume
59
Issue
10
Pages
6460-6501
ISSN
  • 0893-7648 (ISSN-L)
  • 1559-1182
OpenAlex
W4291237996
Cited by
113
References
325
Citations by year
2026: 31 · 2025: 30 · 2024: 33 · 2023: 15 · 2022: 4
FWCI
1.55
Type
journal article
Language
en
Open access
Locations
  • Molecular Neurobiology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
Università degli Studi di Napoli Federico II
Topics
  • Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
  • Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
schizophrenia, inflammation, dopamine-glutamate interaction, dendritic spines, postsynaptic density, NMDA receptor, microglia, maternal immune activation, kynurenine pathway, plasma inflammatory markers, functional connectivity, cognitive impairment, antipsychotic resistance, clozapine, translational research
MeSH terms
Dopamine, Humans, Inflammation, Schizophrenia, Antipsychotic Agents, Receptors, N-Methyl-D-Aspartate, Glutamic Acid

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review