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童年时期经历自杀式爆炸恐怖袭击的成年幸存者单核细胞 NR3C1 SKA2 和 FKPB5 表达水平降低与 PTSD 的发生有关。

Decreased mononuclear cell NR3C1 SKA2 and FKPB5 expression levels among adult survivors of suicide bombing terror attacks in childhood are associated with the development of PTSD.

机构信息

Molecular Psychiatry Laboratory, Department of Psychiatry, Hadassah Medical Organization and Faculty of Medicine, Hebrew University, Jerusalem, Israel.

The Herman-Danna Division of Pediatric Psychiatry, Department of Psychiatry, Hadassah Medical Organization and Faculty of Medicine, Hebrew University, Jerusalem, Israel.

出版信息

Mol Psychiatry. 2023 Sep;28(9):3851-3855. doi: 10.1038/s41380-023-02278-7. Epub 2023 Oct 16.

DOI:10.1038/s41380-023-02278-7
PMID:37845495
Abstract

Life threatening trauma and the development of PTSD during childhood, may each associate with transcriptional perturbation of immune cell glucocorticoid reactivity, yet their separable longer term contributions are less clear. The current study compared resting mononuclear cell gene expression levels of the nuclear receptor, subfamily 3, member 1 (NR3C1) coding the glucocorticoid receptor, its trans-activator spindle and kinetochore-associated protein 2 (SKA2), and its co-chaperon FKBP prolyl isomerase 5 (FKBP5), between a cohort of young adults first seen at the Hadassah Emergency Department (ED) after surviving a suicide bombing terror attack during childhood, and followed longitudinally over the years, and matched healthy controls not exposed to life threatening trauma. While significant reductions in mononuclear cell gene expression levels were observed among young adults for all three transcripts following early trauma exposure, the development of subsequent PTSD beyond trauma exposure, accounted for a small but significant portion of the variance in each of the three transcripts. Long-term perturbation in the expression of immune cell glucocorticoid response transcripts persists among young adults who develop PTSD following life threatening trauma exposure in childhood, denoting chronic dysregulation of immune stress reactivity.

摘要

生命威胁性创伤和儿童期创伤后应激障碍(PTSD)的发展,都可能与免疫细胞糖皮质激素反应的转录扰动有关,但它们在长期的分离贡献尚不清楚。本研究比较了一组在童年时期经历自杀式爆炸恐怖袭击后,首次在哈达萨急诊部(ED)就诊的年轻成年人的静息单核细胞中核受体亚家族 3 成员 1(NR3C1)编码糖皮质激素受体及其转录激活剂纺锤体和着丝粒相关蛋白 2(SKA2)和其共伴侣 FKBP 脯氨酰异构酶 5(FKBP5)的基因表达水平,这些年轻人在多年的时间里进行了纵向随访,并与未经历生命威胁性创伤的健康对照组相匹配。尽管在早期创伤暴露后,所有三种转录物在年轻成年人的单核细胞基因表达水平均显著降低,但在创伤暴露后发生随后的 PTSD 的发展,仅占三种转录物中每种转录物变异性的一小部分。在童年时期经历生命威胁性创伤后发展为 PTSD 的年轻成年人中,免疫细胞糖皮质激素反应转录物的长期表达扰动持续存在,表明免疫应激反应的慢性失调。

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The role of the immune system in posttraumatic stress disorder.免疫系统在创伤后应激障碍中的作用。
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Mol Psychiatry. 2022 Aug;27(8):3150-3163. doi: 10.1038/s41380-022-01564-0. Epub 2022 Apr 27.
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Preclinical animal models of mental illnesses to translate findings from the bench to the bedside: Molecular brain mechanisms and peripheral biomarkers associated to early life stress or immune challenges.将研究成果从实验室转化到临床的精神疾病临床前动物模型:与早期生活压力或免疫应激相关的分子脑机制和外周生物标志物。
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