躯体症状障碍患儿糖皮质激素受体基因的甲基化:一项病例对照研究。

Methylation of the Glucocorticoid Receptor Gene in Children with Somatic Symptom Disorder: A Case-Control Study.

作者信息

Hatta Kyoko, Kantake Masato, Tanaka Kyoko, Nakaoka Hirofumi, Shimizu Toshiaki, Shoji Hiromichi

机构信息

Department of Pediatrics, Juntendo University Faculty of Medicine, Tokyo 113-0033, Japan.

Department of Neonatology, Juntendo University Nerima Hospital, 3-1-10 Nerima Takanodai, Nerima-ku, Tokyo 177-8521, Japan.

出版信息

Epigenomes. 2025 Jun 13;9(2):22. doi: 10.3390/epigenomes9020022.

Abstract

Somatic symptom disorder (SSD) in children may be influenced by stress reactivity and psychosocial factors. The glucocorticoid receptor (GR), encoded by NR3C1, is a key mediator of stress responses. However, the relationship between NR3C1 methylation and SSD remains unclear. We analyzed NR3C1 exon 1F methylation in cell-free DNA from saliva in 34 children with SSD and 29 age- and sex-matched controls using bisulfite amplicon sequencing. Psychological assessments included the Beck Depression Inventory-II (BDI-II) and KINDL questionnaires to evaluate associations with methylation patterns. Methylation levels showed age-related differences. In children under 13, CpG sites displayed mixed methylation, and specific sites correlated with KINDL and BDI-II scores. KINDL physical and total well-being scores negatively correlated with CpG30 and positively with CpG35; BDI-II scores negatively correlated with CpG32 and CpG35. In children aged 13 or older, CpG sites showed uniformly high methylation with no correlation to psychological measures. The SSD group showed significantly higher average methylation across the exon 1F region than controls in the older age group. These children also had more cases of orthostatic dysregulation and longer illness duration. This study suggests age-dependent epigenetic regulation of NR3C1 in SSD. While younger children showed CpG-specific correlations with psychological symptoms, older children demonstrated uniformly high methylation and potentially reduced gene expression, potentially reflecting cumulative stress, autonomic dysfunction, and internalizing disorders such as anxiety and depression.

摘要

儿童的躯体症状障碍(SSD)可能受应激反应性和心理社会因素影响。由NR3C1编码的糖皮质激素受体(GR)是应激反应的关键介质。然而,NR3C1甲基化与SSD之间的关系仍不清楚。我们使用亚硫酸氢盐扩增子测序分析了34例SSD儿童和29例年龄及性别匹配的对照儿童唾液中游离DNA的NR3C1外显子1F甲基化情况。心理评估包括贝克抑郁量表第二版(BDI-II)和儿童青少年生活质量量表(KINDL)问卷,以评估与甲基化模式的关联。甲基化水平呈现出与年龄相关的差异。在13岁以下儿童中,CpG位点呈现混合甲基化,特定位点与KINDL和BDI-II评分相关。KINDL身体和总体幸福感评分与CpG30呈负相关,与CpG35呈正相关;BDI-II评分与CpG32和CpG35呈负相关。在13岁及以上儿童中,CpG位点呈现一致的高甲基化,与心理测量指标无相关性。SSD组在1F区域外显子的平均甲基化水平显著高于老年对照组。这些儿童直立性调节障碍的病例也更多,病程更长。本研究表明,SSD中NR3C1存在年龄依赖性的表观遗传调控。年幼的儿童显示出CpG位点与心理症状的特异性关联,而年长的儿童则表现出一致的高甲基化以及可能降低的基因表达,这可能反映了累积应激、自主神经功能障碍以及焦虑和抑郁等内化障碍。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8aaf/12192148/6b8371cee0eb/epigenomes-09-00022-g001.jpg

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