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

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

Journal of psychiatry & neuroscience, 2016-05, Vol.41 (3), p.E46-E55 [Periódico revisado por pares]

Canada: Joule Inc

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Título:
Evidence of activation of the Toll-like receptor-4 proinflammatory pathway in patients with schizophrenia
Autor: García-Bueno, Borja, PhD ; MacDowell, Karina S., PhD ; Leza, Juan C., PhD, MD ; Callado, Luis F., PhD, MD ; Meana, J. Javier, PhD, MD ; Mas, Sergi, PhD ; Lafuente, Amalia, PhD ; Bernardo, Miguel, PhD, MD ; Gassó, Patricia, PhD
Assuntos: Adult ; Aged ; Antipsychotic Agents - therapeutic use ; Esquizofrènia ; Female ; Genetic Association Studies ; Genetic Predisposition to Disease ; Health aspects ; Humans ; Immune response ; Inflamació ; Inflammation ; Malalties mentals ; Male ; Medical Education ; Mental illness ; Middle Aged ; Myeloid Differentiation Factor 88 - genetics ; Myeloid Differentiation Factor 88 - metabolism ; NF-kappa B - metabolism ; Observations ; Physiological aspects ; Polymorphism, Single Nucleotide ; Prefrontal Cortex - drug effects ; Prefrontal Cortex - immunology ; Psychiatry ; Psychopathology ; Psychosis ; Research Paper ; Retrospective Studies ; RNA, Messenger ; Schizophrenia ; Schizophrenia - drug therapy ; Schizophrenia - genetics ; Schizophrenia - metabolism ; Signal Transduction ; Studies ; Toll-Like Receptor 4 - metabolism ; Toll-like receptors
É parte de: Journal of psychiatry & neuroscience, 2016-05, Vol.41 (3), p.E46-E55
Notas: ObjectType-Article-1
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These authors contributed equally to this work.
Descrição: Background Alterations 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. Methods We 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. Results We 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. Conclusion The 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.
Editor: Canada: Joule Inc
Idioma: Inglês

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

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

Canada: Joule Inc

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