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抗精神病药物治疗初发精神分裂症患者中主要组织相容性复合体区域单核苷酸多态性与皮质厚度减少相关。

Reduced cortical thickness related to single nucleotide polymorphisms in the major histocompatibility complex region in antipsychotic-naive schizophrenia.

机构信息

Department of Radiology, Center for Medical Imaging, West China Hospital of Sichuan University, Chengdu, China.

State Key Laboratory of Biotherapy, Sichuan University, Chengdu, China.

出版信息

Brain Behav. 2019 May;9(5):e01253. doi: 10.1002/brb3.1253. Epub 2019 Mar 28.

Abstract

The aim of this study was to explore the relationships between changes in cortical thickness and single nucleotide polymorphisms (SNPs) in the major histocompatibility complex (MHC) region in a group of antipsychotic-naive schizophrenia (AN-SCZ) patients. Methods Twenty-five AN-SCZ patients and 51 healthy controls (HCs) participated in this study. General linear models were used to identify associations between the average cortical thicknesses of each brain region (N = 68) and each of the 11 SNPs in the MHC region in the AN-SCZ patients and HCs. Next, we performed independent-sample t tests to investigate whether cortical thickness was significantly lower in the AN-SCZ patients than in HCs in the brain regions that were significantly associated with the SNPs. Finally, we examined the correlations between clinical symptoms and cortical thickness in the above brain areas in the whole AN-SCZ group using Pearson correlation tests. Results Seven of the 11 SNPs within the MHC region were significantly associated with cortical thickness only in the AN-SCZ patients; these included rs1635, rs1736913, rs2021722, rs204999, rs2523722, rs3131296, and rs9272105. The AN-SCZ patients had significantly thinner cortical thicknesses in the above brain regions, especially the prefrontal cortex. Furthermore, the left entorhinal region was negatively correlated with Positive and Negative Symptom Scale (PANSS) activation scores in the AN-SCZ group (r = -0.601, p = 0.03). Conclusions This study provides evidence demonstrating the potential effects of MHC risk variants in cortical thickness deficits in AN-SCZ. These data also support the notion that the immune system plays critical roles in the pathology of schizophrenia, which is mediated via the modulation of the development of cerebral cortical structures.

摘要

本研究旨在探讨一组未经抗精神病药物治疗的精神分裂症(AN-SCZ)患者皮质厚度变化与主要组织相容性复合体(MHC)区域内单核苷酸多态性(SNP)之间的关系。方法 25 名未经抗精神病药物治疗的精神分裂症患者和 51 名健康对照者(HCs)参与了这项研究。采用一般线性模型,确定了 25 名未经抗精神病药物治疗的精神分裂症患者和 51 名健康对照者(HCs)中每个脑区(N=68)的平均皮质厚度与 MHC 区域内的 11 个 SNP 之间的关系。然后,我们进行独立样本 t 检验,以研究在与 SNP 显著相关的脑区中,未经抗精神病药物治疗的精神分裂症患者的皮质厚度是否显著低于 HCs。最后,我们使用 Pearson 相关检验,在整个 AN-SCZ 组中,检查上述脑区的临床症状与皮质厚度之间的相关性。结果 MHC 区域内的 11 个 SNP 中有 7 个仅与 AN-SCZ 患者的皮质厚度显著相关,包括 rs1635、rs1736913、rs2021722、rs204999、rs2523722、rs3131296 和 rs9272105。未经抗精神病药物治疗的精神分裂症患者在上述脑区的皮质厚度明显变薄,尤其是前额叶皮质。此外,左内嗅皮层与 AN-SCZ 组阳性和阴性症状量表(PANSS)激活评分呈负相关(r=-0.601,p=0.03)。结论 本研究提供了证据,证明 MHC 风险变异在未经抗精神病药物治疗的精神分裂症患者皮质厚度缺陷中可能具有潜在影响。这些数据还支持这样一种观点,即免疫系统通过调节大脑皮质结构的发育,在精神分裂症的发病机制中发挥关键作用。

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Major histocompatibility complex I in brain development and schizophrenia.脑发育与精神分裂症中的主要组织相容性复合体 I。
Biol Psychiatry. 2014 Feb 15;75(4):262-8. doi: 10.1016/j.biopsych.2013.10.003. Epub 2013 Oct 10.

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