Evidence map›Paper›PMID 27070349›Full record

ArticleJournal of psychiatry & neuroscience : JPN2016

Evidence of activation of the Toll-like receptor-4 proinflammatory pathway in patients with schizophrenia.

Borja García-Bueno, Patricia Gassó, Karina S MacDowell, Luis F Callado, Sergi Mas, Miguel Bernardo, Amalia Lafuente, J Javier Meana, Juan C Leza

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

Article in Journal of psychiatry & neuroscience : JPN, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed, 1 pooled it
3.1field-weighted citation impact, top 8% 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

45 citing papers in PubMed, 1 synthesis or guideline pooled it, 81 citations in OpenAlex.

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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

9 authors at 6 institutions in 3 countries.

Borja García-BuenoFrom the CIBERSAM. ISCIII, Spain (García-Bueno, MacDowell, Callado, Mas, Bernardo, Lafuente, Meana, Leza); the Department of Pharmacology, School of Medicine, Complutense University & Instituto de Investigación Hospital 12 de Octobre (Imas12). Madrid (García-Bueno, MacDowell, Leza); the Department of Anatomic Pathology, Pharmacology and Microbiology. School of Medicine, University of Barcelona, Barcelona (Gassó, Mas, Lafuente); the Department of Pharmacology, University of Basque Country UPV/EHU and BioCruces Institute, Bizkaia (Callado, Meana); the IDIBAPS (Institut d'Investigacions Biomèdiques August Pi i Sunyer), Barcelona (Gassó, Mas, Bernardo, Lafuente); and the Barcelona Clinic Schizophrenia Unit, Neuroscience Institute, Hospital Clinic of Barcelona. Department of Psychiatry and Clinical Psychobiology, University of Barcelona (Bernardo).
Patricia GassóFrom the CIBERSAM. ISCIII, Spain (García-Bueno, MacDowell, Callado, Mas, Bernardo, Lafuente, Meana, Leza); the Department of Pharmacology, School of Medicine, Complutense University & Instituto de Investigación Hospital 12 de Octobre (Imas12). Madrid (García-Bueno, MacDowell, Leza); the Department of Anatomic Pathology, Pharmacology and Microbiology. School of Medicine, University of Barcelona, Barcelona (Gassó, Mas, Lafuente); the Department of Pharmacology, University of Basque Country UPV/EHU and BioCruces Institute, Bizkaia (Callado, Meana); the IDIBAPS (Institut d'Investigacions Biomèdiques August Pi i Sunyer), Barcelona (Gassó, Mas, Bernardo, Lafuente); and the Barcelona Clinic Schizophrenia Unit, Neuroscience Institute, Hospital Clinic of Barcelona. Department of Psychiatry and Clinical Psychobiology, University of Barcelona (Bernardo).
Karina S MacDowellFrom the CIBERSAM. ISCIII, Spain (García-Bueno, MacDowell, Callado, Mas, Bernardo, Lafuente, Meana, Leza); the Department of Pharmacology, School of Medicine, Complutense University & Instituto de Investigación Hospital 12 de Octobre (Imas12). Madrid (García-Bueno, MacDowell, Leza); the Department of Anatomic Pathology, Pharmacology and Microbiology. School of Medicine, University of Barcelona, Barcelona (Gassó, Mas, Lafuente); the Department of Pharmacology, University of Basque Country UPV/EHU and BioCruces Institute, Bizkaia (Callado, Meana); the IDIBAPS (Institut d'Investigacions Biomèdiques August Pi i Sunyer), Barcelona (Gassó, Mas, Bernardo, Lafuente); and the Barcelona Clinic Schizophrenia Unit, Neuroscience Institute, Hospital Clinic of Barcelona. Department of Psychiatry and Clinical Psychobiology, University of Barcelona (Bernardo).
Luis F CalladoFrom the CIBERSAM. ISCIII, Spain (García-Bueno, MacDowell, Callado, Mas, Bernardo, Lafuente, Meana, Leza); the Department of Pharmacology, School of Medicine, Complutense University & Instituto de Investigación Hospital 12 de Octobre (Imas12). Madrid (García-Bueno, MacDowell, Leza); the Department of Anatomic Pathology, Pharmacology and Microbiology. School of Medicine, University of Barcelona, Barcelona (Gassó, Mas, Lafuente); the Department of Pharmacology, University of Basque Country UPV/EHU and BioCruces Institute, Bizkaia (Callado, Meana); the IDIBAPS (Institut d'Investigacions Biomèdiques August Pi i Sunyer), Barcelona (Gassó, Mas, Bernardo, Lafuente); and the Barcelona Clinic Schizophrenia Unit, Neuroscience Institute, Hospital Clinic of Barcelona. Department of Psychiatry and Clinical Psychobiology, University of Barcelona (Bernardo).
Sergi MasFrom the CIBERSAM. ISCIII, Spain (García-Bueno, MacDowell, Callado, Mas, Bernardo, Lafuente, Meana, Leza); the Department of Pharmacology, School of Medicine, Complutense University & Instituto de Investigación Hospital 12 de Octobre (Imas12). Madrid (García-Bueno, MacDowell, Leza); the Department of Anatomic Pathology, Pharmacology and Microbiology. School of Medicine, University of Barcelona, Barcelona (Gassó, Mas, Lafuente); the Department of Pharmacology, University of Basque Country UPV/EHU and BioCruces Institute, Bizkaia (Callado, Meana); the IDIBAPS (Institut d'Investigacions Biomèdiques August Pi i Sunyer), Barcelona (Gassó, Mas, Bernardo, Lafuente); and the Barcelona Clinic Schizophrenia Unit, Neuroscience Institute, Hospital Clinic of Barcelona. Department of Psychiatry and Clinical Psychobiology, University of Barcelona (Bernardo).
Miguel BernardoFrom the CIBERSAM. ISCIII, Spain (García-Bueno, MacDowell, Callado, Mas, Bernardo, Lafuente, Meana, Leza); the Department of Pharmacology, School of Medicine, Complutense University & Instituto de Investigación Hospital 12 de Octobre (Imas12). Madrid (García-Bueno, MacDowell, Leza); the Department of Anatomic Pathology, Pharmacology and Microbiology. School of Medicine, University of Barcelona, Barcelona (Gassó, Mas, Lafuente); the Department of Pharmacology, University of Basque Country UPV/EHU and BioCruces Institute, Bizkaia (Callado, Meana); the IDIBAPS (Institut d'Investigacions Biomèdiques August Pi i Sunyer), Barcelona (Gassó, Mas, Bernardo, Lafuente); and the Barcelona Clinic Schizophrenia Unit, Neuroscience Institute, Hospital Clinic of Barcelona. Department of Psychiatry and Clinical Psychobiology, University of Barcelona (Bernardo).
Amalia LafuenteFrom the CIBERSAM. ISCIII, Spain (García-Bueno, MacDowell, Callado, Mas, Bernardo, Lafuente, Meana, Leza); the Department of Pharmacology, School of Medicine, Complutense University & Instituto de Investigación Hospital 12 de Octobre (Imas12). Madrid (García-Bueno, MacDowell, Leza); the Department of Anatomic Pathology, Pharmacology and Microbiology. School of Medicine, University of Barcelona, Barcelona (Gassó, Mas, Lafuente); the Department of Pharmacology, University of Basque Country UPV/EHU and BioCruces Institute, Bizkaia (Callado, Meana); the IDIBAPS (Institut d'Investigacions Biomèdiques August Pi i Sunyer), Barcelona (Gassó, Mas, Bernardo, Lafuente); and the Barcelona Clinic Schizophrenia Unit, Neuroscience Institute, Hospital Clinic of Barcelona. Department of Psychiatry and Clinical Psychobiology, University of Barcelona (Bernardo).
J Javier MeanaFrom the CIBERSAM. ISCIII, Spain (García-Bueno, MacDowell, Callado, Mas, Bernardo, Lafuente, Meana, Leza); the Department of Pharmacology, School of Medicine, Complutense University & Instituto de Investigación Hospital 12 de Octobre (Imas12). Madrid (García-Bueno, MacDowell, Leza); the Department of Anatomic Pathology, Pharmacology and Microbiology. School of Medicine, University of Barcelona, Barcelona (Gassó, Mas, Lafuente); the Department of Pharmacology, University of Basque Country UPV/EHU and BioCruces Institute, Bizkaia (Callado, Meana); the IDIBAPS (Institut d'Investigacions Biomèdiques August Pi i Sunyer), Barcelona (Gassó, Mas, Bernardo, Lafuente); and the Barcelona Clinic Schizophrenia Unit, Neuroscience Institute, Hospital Clinic of Barcelona. Department of Psychiatry and Clinical Psychobiology, University of Barcelona (Bernardo).
Juan C LezaFrom the CIBERSAM. ISCIII, Spain (García-Bueno, MacDowell, Callado, Mas, Bernardo, Lafuente, Meana, Leza); the Department of Pharmacology, School of Medicine, Complutense University & Instituto de Investigación Hospital 12 de Octobre (Imas12). Madrid (García-Bueno, MacDowell, Leza); the Department of Anatomic Pathology, Pharmacology and Microbiology. School of Medicine, University of Barcelona, Barcelona (Gassó, Mas, Lafuente); the Department of Pharmacology, University of Basque Country UPV/EHU and BioCruces Institute, Bizkaia (Callado, Meana); the IDIBAPS (Institut d'Investigacions Biomèdiques August Pi i Sunyer), Barcelona (Gassó, Mas, Bernardo, Lafuente); and the Barcelona Clinic Schizophrenia Unit, Neuroscience Institute, Hospital Clinic of Barcelona. Department of Psychiatry and Clinical Psychobiology, University of Barcelona (Bernardo).
BioCruces Health research Institute · ESCentro de Investigación Biomédica en Red de Salud Mental · ESUniversitat de Barcelona · ESHospital Clínic de Barcelona · ESNeuroscience Institute · ITUniversity of the Basque Country · ES

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAlterations in the innate immune/inflammatory system may underlie the pathophysiology of schizophrenia, but we do not understand the mechanisms involved. The main agents of innate immunity are the Toll-like receptors (TLRs), which detect molecular patterns associated with damage and pathogens. The TLR first reported was TLR4, and it is still the most studied one.

methodsWe aimed to describe putative modifications to the TLR4 proinflammatory pathway using 2 different strategies in 2 cohorts of patients with schizophrenia and matched controls: 1) quantification of protein and mRNA expression in postmortem prefrontal cortex samples from 30 patients with schizophrenia and 30 controls, and 2) identification of single nucleotide polymorphisms associated with the risk of schizophrenia using whole blood samples from 214 patients with schizophrenia and 216 controls.

resultsWe found evidence of alterations in the expression of the initial elements of the TLR4 signalling pathway (TLR4, Myeloid differentiation primary response gene 88 [MyD88] and nuclear factor-κ B [NF-κB]) in the PFC of patients with schizophrenia. These alterations seem to depend on the presence/absence of antipsychotic treatment at death. Moreover, a polymorphism within the MyD88 gene was significantly associated with schizophrenia risk. LIMITATIONS: The use of 2 different approaches in 2 different cohorts, the lack of a complementary neuropsychiatric group, the possible confounding effects of antipsychotic treatment and suicide are the main limitations of our study.

conclusionThe evidence from this dual approach suggests there is an altered innate immune response in patients with chronic schizophrenia in which the TLR4 proinflammatory pathway could be affected. Improved understanding of the stimuli and mechanisms responsible for this response could lead to improved schizophrenia treatment and better control of the side effects of current antipsychotics.

Indexed as

Polymorphism, Single NucleotideAdultAgedAntipsychotic AgentsFemaleGenetic Association StudiesGenetic Predisposition to DiseaseHumansMaleMiddle AgedMyeloid Differentiation Factor 88NF-kappa BPrefrontal CortexRetrospective StudiesRNA, MessengerSchizophreniaAntipsychotic AgentsMYD88 protein, humanMyeloid Differentiation Factor 88NF-kappa BRNA, MessengerTLR4 protein, humanToll-Like Receptor 4

Identifiers

PMID27070349
PMCPMC4853215
OpenAlexW2339925206

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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.