Melika Jameie, Sanaz Bordbar, Reza Samiee, Mobina Amanollahi, Mehdi Azizmohammad Looha, Mir Sajjad Aleyasin, Mohammad Reza Abdol Homayuni, Mehrdad Mozafar, Seyed Behnamedin Jameie, Shahin Akhondzadeh
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No significant difference was found between the groups in terms of TLR4+ monocytes percentage (Hedges' g = 0.235 [-0.245, 0.715], τ2 = 0.31, I2 = 87.30%) or TLR4 gene expression (Hedges' g = 0.179 [-0.502, 0.861], τ2 = 0.29, I2 = 79.04%). According to qualitative synthesis, TLR4 stimulation resulted in reduced monocytic activation in PwSCZ compared to HCs.</p><p><strong>Conclusions: </strong>This study suggested a trend toward an increased basal monocytic TLR4 density in PwSCZ, with no difference in the basal percentage of TLR4+ monocytes or TLR4 gene expression. 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引用次数: 0
摘要
背景：toll样受体4 （TLR4）在精神分裂症中的作用尚不清楚，研究报告了其在精神分裂症患者（PwSCZ）中的表达和激活的相互矛盾的结果。这项系统综述/荟萃分析比较了PwSCZ和健康对照（hc）之间的基础单核细胞TLR4表达及其激活模式。方法：本研究在PROSPERO注册（CRD42021273858），并遵守PRISMA指南。通过MEDLINE（通过PubMed）、Web of Science和Scopus进行了系统的检索，从创立到2023年12月12日。定量合成(a)基础单核细胞TLR4密度，(b)基础TLR4+单核细胞百分比，(c)基础TLR4基因表达。效应量使用Hedges’g计算平均差异。采用限制最大似然估计的随机效应模型，并根据抗精神病状态进行亚分组。这些研究的偏倚风险是用乔安娜布里格斯研究所（JBI）的工具来评估的。结果：纳入11项研究（473例PwSCZ， 416例hc）。合并分析显示，PwSCZ的基础单核细胞TLR4密度增加趋势不显著（Hedges' g = 0.317 [95% CI: -0.060, 0.694], τ2 = 0.127, I2 = 68.91%）。在进行敏感性分析并排除一项研究后，差异变得显著（Hedges' g = 0.469 [0.195,0.742], p = 0.001）。各组间TLR4+单核细胞百分比（Hedges' g = 0.235 [-0.245, 0.715], τ2 = 0.31, I2 = 87.30%）和TLR4基因表达（Hedges' g = 0.179 [-0.502, 0.861], τ2 = 0.29, I2 = 79.04%）差异均无统计学意义。根据定性合成，与hc相比，TLR4刺激导致PwSCZ的单核细胞活化降低。结论：本研究提示PwSCZ的基础单核细胞TLR4密度有增加的趋势，而TLR4+单核细胞的基础百分比或TLR4基因表达没有差异。然而，有限的可用数据强调了未来研究的必要性。
Monocytic TLR4 expression and activation in schizophrenia: A systematic review and meta-analysis.
Background: The role of toll-like receptor 4 (TLR4) in schizophrenia remains unclear, with studies reporting conflicting results on its expression and activation in persons with schizophrenia (PwSCZ). This systematic review/meta-analysis compared basal monocytic TLR4 expression, as well as its activation pattern between PwSCZ and healthy controls (HCs).
Methods: This study was registered with PROSPERO (CRD42021273858) and adhered to the PRISMA guidelines. A systematic search was conducted through MEDLINE (via PubMed), Web of Science, and Scopus from inception to December 12, 2023. Quantitative syntheses were conducted for (a) basal monocytic TLR4 density, (b) basal percentage of TLR4+ monocytes, and (c) basal TLR4 gene expression. Effect sizes were computed using Hedges' g for mean differences. Random-effect models with restricted maximum-likelihood estimation were used, and subgrouping was conducted based on antipsychotic status. The studies' risk of bias was assessed using the Joanna Briggs Institute (JBI) tool.
Results: Eleven studies (473 PwSCZ, 416 HCs) were included. Pooled analysis revealed a nonsignificant trend toward increased basal monocytic TLR4 density in PwSCZ (Hedges' g = 0.317 [95% CI: -0.060, 0.694], τ2 = 0.127, I2 = 68.91%). The difference became significant after sensitivity analysis and excluding one study (Hedges' g = 0.469 [0.195,0.742], p = 0.001). No significant difference was found between the groups in terms of TLR4+ monocytes percentage (Hedges' g = 0.235 [-0.245, 0.715], τ2 = 0.31, I2 = 87.30%) or TLR4 gene expression (Hedges' g = 0.179 [-0.502, 0.861], τ2 = 0.29, I2 = 79.04%). According to qualitative synthesis, TLR4 stimulation resulted in reduced monocytic activation in PwSCZ compared to HCs.
Conclusions: This study suggested a trend toward an increased basal monocytic TLR4 density in PwSCZ, with no difference in the basal percentage of TLR4+ monocytes or TLR4 gene expression. However, the limited available data underscores the need for future studies.
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