Antipsychotics influence Toll-like receptor (TLR) expression and its relationship with cognitive functions in schizophrenia

Kéri, Szabolcs; Szabó, Csilla; Kelemen, Ogúz

doi:10.1016/j.bbi.2016.12.011

Cited by 43 publications

(36 citation statements)

References 60 publications

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“…A study that evaluated 24 schizophrenic patients after 8 weeks of treatment (10-25 mg/day) exhibited that this drug increased TLR2 expression and decreased TLR4 and TLR5 in CD14 + monocytes. Treg and Tact cells reduced TLR2 and increased TLR5 expression (186). In 23 patients diagnosed with schizophrenia and treated with olanzapine for 8 weeks, IL-1RA was overexpressed, which correlated with the increase in leptin (210) (see Table 2).…”

Section: Olanzapinementioning

confidence: 98%

“…In schizophrenic patients, risperidone (8 weeks, 2-6 mg/day) modifies the expression of toll-like receptors (TLR), while monocytes CD14 + , CD3 + CD4 + Foxp3 + T, and CD3 + CD4 + CD25 + T cells increased TLR2 expression, and CD14 + monocytes decreased TLR4 expression (185). Effects on gene expression have been reported; in blood cells of firstepisode psychosis patients, risperidone (unspecified doses, 20 days) was associated to the up-regulation of 11 immune system genes, including cytokines and cytokine receptors (SPP1, IL1R1, IL1R2), pattern recognition molecules (TLR1, TLR2, TLR6, dectin-1/CLEC7a), molecules involved in apoptosis (FAS), and BDKRB1, IGF1R, and CR1 (186).…”

Section: Risperidonementioning

confidence: 99%

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Immunoendocrine Peripheral Effects Induced by Atypical Antipsychotics

et al. 2020

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Atypical antipsychotics (AAP) or second-generation antipsychotics are the clinical option for schizophrenia treatment during acute psychoses, but they are also indicated for maintenance during lifetime, even though they are being used for other psychiatric conditions in clinical practice such as affective disorders and autism spectrum disorder, among others. These drugs are differentiated from typical antipsychotics based on their clinical profile and are a better choice because they cause fewer side effects regarding extrapyramidal symptoms (EPS). Even though they provide clear therapeutic benefits, AAP induce peripheral effects that trigger phenotypic, functional, and systemic changes outside the Central Nervous System (CNS). Metabolic disease is frequently associated with AAP and significantly impacts the patient's quality of life. However, other peripheral changes of clinical relevance are present during AAP treatment, such as alterations in the immune and endocrine systems as well as the intestinal microbiome. These less studied alterations also have a significant impact in the patient's health status. This manuscript aims to revise the peripheral immunological, endocrine, and intestinal microbiome changes induced by AAP consumption recommended in the clinical guidelines for schizophrenia and other psychiatric disorders.

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Section: Olanzapinementioning

confidence: 98%

Section: Risperidonementioning

confidence: 99%

Immunoendocrine Peripheral Effects Induced by Atypical Antipsychotics

et al. 2020

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“…Indeed, TLR2 and TLR4 knockout mice showed subtle impairments in behavior and cognitive functions (Park et al, 2015 ; Too et al, 2016 ). A clinical study in subjects diagnosed with psychotic disorders showed specific alterations in TLR agonist-mediated cytokine release compared to healthy controls (McKernan et al, 2011 ), and more recently it has been shown that abnormal expression of TLRs can be modulated by antipsychotics (Kéri et al, 2017 ). Moreover, in post-mortem prefrontal cortex samples from subjects diagnosed with psychosis, alterations in TLR4 have been shown, which were dependent on antipsychotic treatment status at time of death (García-Bueno et al, 2016 ).…”

Section: Mechanistic Influences Of Microbiota On Brain Function and Dmentioning

confidence: 99%

Cross Talk: The Microbiota and Neurodevelopmental Disorders

et al. 2017

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Humans evolved within a microbial ecosystem resulting in an interlinked physiology. The gut microbiota can signal to the brain via the immune system, the vagus nerve or other host-microbe interactions facilitated by gut hormones, regulation of tryptophan metabolism and microbial metabolites such as short chain fatty acids (SCFA), to influence brain development, function and behavior. Emerging evidence suggests that the gut microbiota may play a role in shaping cognitive networks encompassing emotional and social domains in neurodevelopmental disorders. Drawing upon pre-clinical and clinical evidence, we review the potential role of the gut microbiota in the origins and development of social and emotional domains related to Autism spectrum disorders (ASD) and schizophrenia. Small preliminary clinical studies have demonstrated gut microbiota alterations in both ASD and schizophrenia compared to healthy controls. However, we await the further development of mechanistic insights, together with large scale longitudinal clinical trials, that encompass a systems level dimensional approach, to investigate whether promising pre-clinical and initial clinical findings lead to clinical relevance.

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“…In addition to examining the effect of antipsychotics on cytokine expression, which may indicate activation of innate or adaptive immunity, antipsychotic actions on innate immunity have been investigated by measuring effects on TLR-4 [32]. TLR-4 is an important PRR that responds to immune stimuli, such as the bacterial endotoxin lipopolysaccharide (LPS), initiating an inflammatory response.…”

Section: Treatmentsmentioning

confidence: 99%