童年虐待与抑郁症状：NR3C1甲基化与反刍的中介作用
Childhood Maltreatment and Depressive Symptoms: Mediating Roles of Glucocorticoid Receptor Gene (NR3C1) Methylation and Rumination
岳欣怡 1曹衍淼 1丁晓凡 1孙宇航 1张文新1
作者信息
- 1. 山东省脑科学与心理健康重点实验室;山东师范大学心理学部
- 折叠
摘要
童年虐待的消极影响会通过生物嵌入方式持续到成年期，改变个体的思维方式进而引发抑郁症状。通过对593名成年早期被试(19.47岁，49.2%女生)进行为期半年的追踪，考察童年期虐待经由NR3C1甲基化、反刍影响成年抑郁症状的链式中介机制。结果显示：(1)不同类型的虐待均会通过增加反刍导致更多的抑郁症状。(2)相比其他类型的虐待，仅情感忽视能够上调NR3C1启动子DNA甲基化水平，使个体陷入更多的反刍思维，进而增加抑郁风险。
Abstract
Childhood maltreatment is a major global public health problem that increases the risk of depressive symptoms later in life. However, important gaps remain in our understanding of how such experiences get under the skin. Emerging evidence suggests that early adversity contributes to epigenetic modifications of key regulatory elements within the hypothalamic-pituitary-adrenal (HPA) axis, potentially increasing vulnerability to psychopathology. In addition, ruminationthe tendency to repetitively dwell on ones problems, concerns, and distressing feelingsrepresents a key cognitive mechanism. Crucially, biological embedding and cognitive processes do not operate in isolation. According to transdiagnostic models of psychopathology, distal environmental risks may heighten rumination by undermining adaptive stress responses. Moreover, because specific subtypes of childhood maltreatment may have distinct epigenetic signatures and differential contributions to depression severity, these mechanisms may vary across maltreatment subtypes. Accordingly, this study examined whether methylation changes in the promoter region of the NR3C1 gene and rumination explain the longitudinal association between childhood maltreatment and adult depressive symptoms, and whether maltreatment subtypes differ in their predictive validity.A total of 593 Chinese young adults (Mage = 19.47 0.69 years; 49.2% female; 98.6% Han Chinese) were recruited from Shandong, China, and followed for six months. Depressive symptoms were assessed at both time points using self-report questionnaires, and childhood maltreatment was assessed retrospectively. Genomic DNA was extracted from buccal swab samples and used for DNA methylation analyses. We tested a series of serial mediation models in which childhood maltreatment predicted depressive symptoms in young adulthood through DNA methylation in the NR3C1 promoter region and rumination in sequence. We also examined whether different childhood maltreatment subtypes showed differential predictive validity.Results showed that DNA methylation of NR3C1 and rumination mediated the longitudinal association between childhood emotional neglect and depressive symptoms in young adulthood. Specifically, emotional neglect was associated with higher methylation levels in the NR3C1 promoter region, which in turn predicted greater rumination and higher depressive symptoms. In addition, all maltreatment subtypes were associated with depressive symptoms via elevated rumination. However, the serial mediation pathway was not observed for childhood emotional abuse, physical abuse, physical neglect, or total maltreatment. Moreover, NR3C1 promoter methylation did not significantly mediate the associations between any childhood maltreatment subtype and depressive symptoms in young adulthood.These findings highlight the importance of epigenetic processes and cognitive vulnerability in understanding how childhood adversity increases risk for depressive symptoms across the lifespan. Notably, this study provides further support for transdiagnostic models of psychopathology, which propose that distal environmental risks can shape individuals stress responses, giving rise to proximal cognitive risk factors that, in turn, precipitate psychopathological symptoms. In addition, the results suggest that distinguishing among subtypes of childhood maltreatment may help clarify the pathways through which maltreatment contributes to depressive symptoms. Specifically, different maltreatment subtypes may exhibit distinct epigenetic signatures, while also sharing common mechanismssuch as rumination in the present studyin the development of depressive symptoms.By identifying epigenetic (NR3C1 methylation) and cognitive (rumination) vulnerability markers, as well as their roles in the development of depressive symptoms, this study has important implications for prevention and intervention. First, these vulnerability markers at the molecular and cognitive levels may facilitate early screening to identify individuals at high risk for depressive disorders. Second, this study calls for early interventions tailored to specific maltreatment subtypes. Prioritizing early family-based programs, parenting support, and cognitive strategies to reduce ruminationand tailoring these approaches to different maltreatment experiences and pathwaysmay interrupt risk transmission, curb symptom escalation, and ultimately reduce the long-term burden of depression.关键词
抑郁症状/童年期虐待/反刍/NR3C1甲基化Key words
depressive symptoms/childhood maltreatment/rumination/NR3C1 methylation引用本文复制引用
岳欣怡,曹衍淼,丁晓凡,孙宇航,张文新.童年虐待与抑郁症状：NR3C1甲基化与反刍的中介作用[EB/OL].(2026-03-04)[2026-03-07].https://chinaxiv.org/abs/202603.00033.学科分类
神经病学、精神病学/遗传学/分子生物学
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