Xu Yajing, Yang Shan, Cao Cong
School of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong University, Jinan, PR China.
School of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong University, Jinan, PR China.
Neuroimage. 2025 Feb 1;306:121003. doi: 10.1016/j.neuroimage.2025.121003. Epub 2025 Jan 6.
Although epigenomic and environment interactions (Epigenome × Environment; Epi × E) might constitute a novel mechanism underlying reward processing, direct evidence is still scarce. We conducted the first longitudinal study to investigate the extent to which DNA methylation of a stress-related gene-NR3C1-interacts with childhood maltreatment in association with young adult reward responsiveness (RR) and the downstream risk of depressive (anhedonia dimension in particular) and anxiety symptoms.
A total of 192 Chinese university students aged 18∼25 (M = 21.08 ± 1.91 years; 59.4% females) were followed in two waves. Reward positivity (RewP) and its time‒frequency components were elicited via a classic monetary reward task. Cytosine methylation in the promoter exon 1F of NR3C1 (NR3C1-1F) was sequenced via buccal cells. Childhood maltreatment, self-reported RR and depressive and anxiety symptoms were assessed via questionnaires.
NR3C1-1F methylation significantly interacted with childhood maltreatment on RewP but not the delta and theta components or self-reported RR. The severity and exposure number of childhood maltreatment were negatively associated with RewP among individuals with heightened NR3C1-1F methylation but positively associated with RewP among individuals with blunted NR3C1-1F methylation, demonstrating a "goodness-of-fit" interaction. This interaction was specifically linked with anhedonia dimension but not with total scores of depressive or anxiety symptoms.
The current findings provide preliminary evidence for an Epi × E interaction underlying reward processing, highlight cross-level analyses of electrophysiological signals and advance knowledge of the biological foundation of stress-induced reward function and relevant symptoms. However, caution should be paid to the generalizability of these findings in high-risk clinical samples given the high-functioning characteristic of the present sample.
尽管表观基因组与环境的相互作用（表观基因组×环境；Epi×E）可能构成奖励处理的一种新机制，但直接证据仍然匮乏。我们开展了第一项纵向研究，以调查与应激相关的基因NR3C1的DNA甲基化与童年期虐待相关联的程度，以及与青年期奖励反应性（RR）及抑郁（尤其是快感缺失维度）和焦虑症状的下游风险之间的关系。
对192名年龄在18至25岁之间的中国大学生（平均年龄M = 21.08 ± 1.91岁；59.4%为女性）进行了两期跟踪研究。通过经典货币奖励任务诱发奖励积极性（RewP）及其时频成分。通过口腔细胞对NR3C1基因启动子外显子1F（NR3C1-1F）中的胞嘧啶甲基化进行测序。通过问卷调查评估童年期虐待、自我报告的RR以及抑郁和焦虑症状。
NR3C1-1F甲基化与童年期虐待在RewP上存在显著的交互作用，但在δ和θ成分或自我报告的RR上不存在交互作用。童年期虐待的严重程度和暴露次数在NR3C1-1F甲基化水平较高的个体中与RewP呈负相关，但在NR3C1-1F甲基化水平较低的个体中与RewP呈正相关，表明存在“拟合优度”交互作用。这种交互作用与快感缺失维度特别相关，但与抑郁或焦虑症状的总分无关。
目前的研究结果为奖励处理背后的Epi×E相互作用提供了初步证据，强调了对电生理信号的跨层次分析，并推进了对应激诱导的奖励功能及相关症状生物学基础的认识。然而，鉴于本样本的高功能特征，对于这些研究结果在高风险临床样本中的普遍性应谨慎对待。
