TGF-β1 is associated with deficits in cognition and cerebral cortical thickness in first-episode schizophrenia.
TGF-β1 is associated with deficits in cognition and cerebral cortical thickness in first-episode schizophrenia.
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DOI：
10.1503/jpn.210121
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发表时间：
2022-03
影响因子：
4.3
通讯作者：
Tian, Li
中科院分区：
文献类型：
--
作者：
Pan, Shujuan;Zhou, Yanfang;Yan, Ling;Xuan, Fangling;Tong, Jinghui;Li, Yanli;Huang, Junchao;Feng, Wei;Chen, Song;Cui, Yimin;Yang, Fude;Tan, Shuping;Wang, Zhiren;Tian, Baopeng;Hong, L. Elliot;Tan, Yun-Long;Tian, Li
有证据表明，细胞因子与精神分裂症的认知缺陷有关;然而，潜在的脑行为机制仍不清楚。我们假设脑结构连接的异常介导了精神分裂症中的细胞因子效应。在这项研究中，我们招募了75例首发精神分裂症患者（n = 75，平均病程12.3个月，平均用药时间0.6天）和44例健康对照组。我们首先进行全血RNA测序以检测差异表达的基因。我们还探索了从CommonMind Consortium检索的背外侧前额叶皮质（dlPFC）的转录组数据，以进行基因功能聚类;我们通过酶联免疫吸附试验测量了血浆转化生长因子β1（TGF-β1）水平;我们获得了皮质厚度MRI的高分辨率T1加权MRI数据;我们使用经验证的中文版MATRICS共识认知成套测验评估了认知功能。我们比较了精神分裂症患者和对照组的这些参数，并分析了它们之间的关联。与对照组相比，精神分裂症患者在mRNA水平（log 2倍数变化= 0.24;校正p = 0.026）和蛋白水平（12.85 ± 6.01 μg/mL v. 8.46 ± 5.15 μg/mL，校正p < 0.001）上均具有较高的TGF-β1。与健康对照组相比，精神分裂症患者dlPFC中与TGFB 1共表达的基因较少。在精神分裂症患者中，TGF-β1蛋白水平与皮质厚度呈负相关，尤其是外侧枕叶皮质（r =-0.47，校正后p = 0.001），与MATRICS共识认知成套测验视觉学习和记忆领域呈负相关（r =-0.50，校正后p < 0.001）。枕叶外侧皮质厚度对TGF-β1与视觉认知的负相关具有完全中介作用（p < 0.05）。我们没有探讨其他血液细胞因子对神经认知能力和皮质厚度的影响。来自CommonMind Consortium的参与者并不都患有首发精神分裂症，他们也不都是抗精神病药物初治者，因此我们不能排除抗精神病药物对dlPFC中TGF-β1信号传导的影响。我们研究的样本量和横断面设计是额外的限制。这些发现强调了TGF-β1血液水平上调与精神分裂症患者脑结构和功能受损之间的关联。
Evidence indicates that cytokines are associated with cognitive deficits in schizophrenia; however, the underlying brain–behaviour mechanisms remain unclear. We hypothesized that aberrations in brain structural connectivity mediate the cytokine effect in schizophrenia. In this study, we recruited patients with first-episode schizophrenia (n = 75, average illness duration 12.3 months, average medication period 0.6 days) and healthy controls (n = 44) of both sexes. We first conducted whole-blood RNA sequencing to detect differentially expressed genes. We also explored transcriptomic data on the dorsal lateral prefrontal cortices (dlPFC) retrieved from the CommonMind Consortium for gene functional clustering; we measured plasma transforming growth factor β1 (TGF-β1) levels by enzyme-linked immunosorbent assay; we acquired high-resolution T1-weighted MRI data on cortical thickness MRI; and we assessed cognitive function using the validated Chinese version of the MATRICS Consensus Cognitive Battery. We compared these parameters in patients with schizophrenia and controls, and analyzed their associations. Patients with schizophrenia had higher TGF-β1 at both the mRNA level (log2 fold change = 0.24; adjusted p = 0.026) and the protein level (12.85 ± 6.01 μg/mL v. 8.46 ± 5.15 μg/mL, adjusted p < 0.001) compared to controls. Genes coexpressed with TGFB1 in the dlPFC were less abundant in patients with schizophrenia compared to healthy controls. In patients with schizophrenia, TGF-β1 protein levels were inversely correlated with cortical thickness, especially of the lateral occipital cortex (r = −0.47, adjusted p = 0.001), and with the MATRICS Consensus Cognitive Battery visual learning and memory domain (r = −0.50, adjusted p < 0.001). We found a complete mediation effect of the thickness of the lateral occipital cortex on the negative relationship between TGF-β1 and visual cognition (p < 0.05). We did not explore the effect of other blood cytokines on neurocognitive performance and cortical thickness. Participants from the CommonMind Consortium did not all have first-episode schizophrenia and they were not all antipsychotic-naive, so we could not exclude an effect of antipsychotics on TGF-β1 signalling in the dlPFC. The sample size and cross-sectional design of our study were additional limitations. These findings highlighted an association between upregulated blood levels of TGF-β1 and impairments in brain structure and function in schizophrenia.
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影响因子：
11
作者：
Kim, S.;Webster, M. J.
通讯作者：
Webster, M. J.
影响因子：
16.2
作者：
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影响因子：
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作者：
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CICCHETTI, D
影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
Cai HQ;Catts VS;Webster MJ;Galletly C;Liu D;O'Donnell M;Weickert TW;Weickert CS
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Weickert CS