More dampened monocytic Toll-like receptor 4 response to lipopolysaccharide and its association with cognitive function in Chinese Han first-episode patients with schizophrenia

Chen, Song; Tian, Li; Chen, Nan; Xiu, Meihong; Wang, Zhiren; Wang, Yuechan; Tan, Yunlong; Wang, Chuanyue

doi:10.1016/j.schres.2018.11.001

Cited by 16 publications

(27 citation statements)

References 44 publications

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“…Monocytic transcriptomes of patients with schizophrenia had stronger inflammatory gene expression fingerprints (16). Studies including ours also found altered levels of toll-like receptors (TLR) and proinflammatory cytokine responses such as IL-1b in monocytes following stimulation with TLR ligands in schizophrenia (15,17,18).…”

Section: Introductionsupporting

confidence: 53%

“…Five ( 5 ) ml of fresh heparin lithium-anticoagulated peripheral blood samples were collected from 29 FES patients and 27 HC subjects of the above participants after overnight fast, and processed within half an hour for fluorescent staining of cell surface receptors as described previously ( 18 ). The fluorochrome-conjugated antibodies used in this study were 10 μl FITC-labeled mouse anti-human CD14 (Clone M5E2; Catalog Number 555397; BD Biosciences) and 3 μl PerCP-Cy™5.5-labeled mouse anti-human CD16 (Clone B73.1; Catalog Number 565421; BD Biosciences).…”

Section: Methodsmentioning

confidence: 99%

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Monocytic Subsets Impact Cerebral Cortex and Cognition: Differences Between Healthy Subjects and Patients With First-Episode Schizophrenia

et al. 2022

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Monocytes are a highly heterogeneous population subcategorized into classical, intermediate and nonclassical subsets. How monocytes and their subsets may shape brain structures and functions in schizophrenia remains unclear. The primary goal of this cross-sectional study was to investigate monocytic subsets and their specific signature genes in regulation of cerebral cortical thickness and cognitive functions in first-episode schizophrenia (FES) patients. Whole-blood RNA sequencing of 128 FES patients and 111 healthy controls (HCs) were conducted and monocyte-specific differentially expressed genes were further analyzed. The MATRICS Consensus Cognitive Battery (MCCB) test, cortical neuroimaging and flow cytometric staining of peripheral blood monocytic subsets were performed among the participants. Significant changes in expressions of 54 monocytic signature genes were found in patients, especially for intermediate and nonclassical monocytic subsets with the most outstanding alterations being downregulated S100 Calcium Binding Protein A (S100A) and upregulated Interferon Induced Transmembrane Protein (IFITM) family members, respectively. Meanwhile, percentage of blood nonclassical monocytes was decreased in patients. Cortical thicknesses and MCCB performance were expectantly reduced and weaker intra-relationships among monocytic signature genes and cortices, respectively, were noted in patients compared to HCs. Monocytic genes were negatively associated with both cortical thicknesses and cognition in HCs, which was interestingly weakened or even reversed in patients, with nonclassical monocytic genes showing the greatest statistical significance. This study reveals that while monocytes may have negative effects on brain structure and cognition, the ameliorated phenomenon observed in schizophrenia may reflect an (mal)adaptive change of monocytes at early stage of the disorder.

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Section: Introductionsupporting

confidence: 53%

Section: Methodsmentioning

confidence: 99%

Monocytic Subsets Impact Cerebral Cortex and Cognition: Differences Between Healthy Subjects and Patients With First-Episode Schizophrenia

et al. 2022

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“…Monocytic transcriptomes of patients with schizophrenia or bipolar disorder had stronger inflammatory gene expression fingerprints (25). Studies including ours have also found altered levels of toll-like receptors (TLR) and proinflammatory cytokine responses such as IL-1β in monocytes following the stimulation of monocytic TLR4/TLR5 and ErbB in schizophrenia (24,26,27). Another study revealed that monocytic TLR-4 expression was negatively associated with brain volumes of frontal and anterior cingulate regions in FES patients (28).…”

Section: Cd14++cd16+ Intermediate Monocytes Presumably Represent a Transitional Stagementioning

confidence: 57%

“…Five (5) ml of fresh heparin lithium-anticoagulated peripheral blood samples were collected from 29 FES patients and 27 HC subjects of the above participants after overnight fast, and processed within half an hour for fluorescent staining of cell surface receptors as described previously ( 27 ). The fluorochrome-conjugated antibodies used in this study were 10 μl FITC-labeled mouse anti-human CD14 (Clone M5E2; Catalog Number 555397; BD Biosciences) and 3 μl PerCP-Cy™5.5-labeled mouse anti-human CD16 (Clone B73.1; Catalog Number 565421; BD Biosciences).…”

Section: Methodsmentioning

confidence: 99%

Monocytic Subsets and Their Signature Genes Differentially Impact Cortex and Cognition in First-Episode Schizophrenia

Chen

Chithanathan

Fan

et al. 2021

Preprint

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Accumulating evidence supports involvement of innate immunity in the pathophysiology of schizophrenia. Monocytes are a highly heterogeneous population, subcategorized into classical (CD14++CD16-), intermediate (CD14++CD16+) and nonclassical subsets (CD14+CD16++). How monocytic subsets may shape brain structures and functions remains unclear. The primary goal of this cross-sectional study was to investigate the inter-relationships among monocytic subsets and their specific transcriptomic profiles, cerebral cortical thickness, and cognitive functions in first-episode schizophrenia (FES) patients. We performed whole-blood RNA sequencing (RNAseq) in 128 FES patients and 111 healthy controls (HCs) along with MATRICS Consensus Cognitive Battery (MCCB) measurement, as well as neuroimaging and flow cytometry among partial participants. RNAseq revealed significantly changed expressions of 54 monocytic signature genes in FES patients compared to HCs, especially for intermediate and nonclassical monocytic subsets, with the most outstanding alterations being downregulated S100 Calcium Binding Protein A (S100A) and upregulated Interferon Induced Transmembrane Protein (IFITM) family members, respectively. The percentage of nonclassical monocytes was decreased in FES patients. Cortical thicknesses and MCCB performance were expectantly reduced in FES patients too. Interestingly, negative inter-relationships of monocytic signature genes with both cortical thicknesses and cognition were found in HCs, which were weakened or even reversed in FES patients. Furthermore, the lateral occipital cortex fully mediated the negative effect of a classical monocytic gene Ribonuclease A Family Member 2 (RNASE2) on visual learning in patient group. This study suggests that monocytic dysfunctions play an essential role in cognitive deficit of schizophrenia, and their subtypes should be considered in future research.

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“… 29 We found that the 7 MCCB domain scores and composite score were impaired in patients with first-episode schizophrenia, consistent with the results of previous studies. 30 Moreover, CTQ total score was significantly associated with cognitive deficits in patients with first-episode schizophrenia, especially the MCCB visual learning and reasoning and problem-solving ability dimensions. The CTQ total score represents an accumulation of multiple complex traumatic experiences.…”

Section: Discussionmentioning

confidence: 95%

Childhood trauma and cognitive deficits in patients with schizophrenia: mediation by orbitofrontal cortex H-shaped sulci volume

Wang¹,

Yin²,

Feng³

et al. 2022

jpn

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Background: A line of evidence has shown that childhood trauma and patterns of H-shaped sulci in the orbitofrontal cortex (OFC) are associated with cognitive deficits in patients with schizophrenia. Studies have also suggested that childhood trauma is associated with OFC volumetrics. This study investigated the interrelationship between childhood trauma, OFC H-shaped sulci volume and cognitive function in patients with first-episode schizophrenia. We hypothesized that OFC H-shaped sulci volume would mediate the relationship between childhood trauma and cognitive function in patients with first-episode schizophrenia. Methods: We recruited patients with first-episode schizophrenia ( n = 63) and healthy controls ( n = 48), and quantified OFC H-shaped sulci volumes with 3.0 T high-resolution MRI. We assessed cognitive function and childhood trauma experiences using the MATRICS Consensus Cognitive Battery (MCCB) and the Childhood Trauma Questionnaire (CTQ). Results: Patients with first-episode schizophrenia had smaller left OFC H-shaped sulci volumes, more severe childhood trauma experiences and worse cognitive function than healthy controls. CTQ total score and emotional and physical neglect subscores were negatively correlated with left OFC H-shaped sulci volume. CTQ total score and emotional neglect and sexual abuse subscores were negatively correlated with cognitive function in patients with first-episode schizophrenia. Interestingly, the CTQ total score and physical neglect subscore were positively correlated with cognitive function in healthy controls. Left OFC H-shaped sulci volume played a mediating role in CTQ emotional neglect subscore, CTQ total score and MCCB composite score. Limitations: The small sample size and retrospective design need to be considered. Conclusion: Childhood trauma might contribute to cognitive deficits in patients with first-episode schizophrenia by affecting left OFC H-shaped sulci volume. This finding can help in the design of strategies to improve cognitive function in patients with first-episode schizophrenia.

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More dampened monocytic Toll-like receptor 4 response to lipopolysaccharide and its association with cognitive function in Chinese Han first-episode patients with schizophrenia

Cited by 16 publications

References 44 publications

Monocytic Subsets Impact Cerebral Cortex and Cognition: Differences Between Healthy Subjects and Patients With First-Episode Schizophrenia

Monocytic Subsets Impact Cerebral Cortex and Cognition: Differences Between Healthy Subjects and Patients With First-Episode Schizophrenia

Monocytic Subsets and Their Signature Genes Differentially Impact Cortex and Cognition in First-Episode Schizophrenia

Childhood trauma and cognitive deficits in patients with schizophrenia: mediation by orbitofrontal cortex H-shaped sulci volume

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