Glucocorticoid receptor gene (NR3C1) methylation, childhood maltreatment, multilevel reward responsiveness and depressive and anxiety symptoms: A neuroimaging epigenetic study

IF 4.7 2区医学 Q1 NEUROIMAGING

NeuroImage Pub Date : 2025-02-01 DOI:10.1016/j.neuroimage.2025.121003

Yajing Xu, Shan Yang, Cong Cao

{"title":"Glucocorticoid receptor gene (NR3C1) methylation, childhood maltreatment, multilevel reward responsiveness and depressive and anxiety symptoms: A neuroimaging epigenetic study","authors":"Yajing Xu, Shan Yang, Cong Cao","doi":"10.1016/j.neuroimage.2025.121003","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>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—<em>NR3C1</em>—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.</div></div><div><h3>Method</h3><div>A total of 192 Chinese university students aged 18∼25 (<em>M</em><sub>age</sub> = 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 <em>NR3C1</em> (<em>NR3C1</em>-1F) was sequenced via buccal cells. Childhood maltreatment, self-reported RR and depressive and anxiety symptoms were assessed via questionnaires.</div></div><div><h3>Results</h3><div><em>NR3C1</em>-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 <em>NR3C1</em>-1F methylation but positively associated with RewP among individuals with blunted <em>NR3C1</em>-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.</div></div><div><h3>Conclusions</h3><div>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.</div></div>","PeriodicalId":19299,"journal":{"name":"NeuroImage","volume":"306 ","pages":"Article 121003"},"PeriodicalIF":4.7000,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"NeuroImage","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1053811925000035","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"NEUROIMAGING","Score":null,"Total":0}

引用次数: 0

Abstract

Background

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.

Method

A total of 192 Chinese university students aged 18∼25 (M_age = 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.

Results

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.

Conclusions

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.

查看原文本刊更多论文

糖皮质激素受体基因（NR3C1）甲基化儿童虐待多层次奖励反应与抑郁和焦虑症状：一项神经影像学表观遗传学研究

背景：虽然表观基因组与环境相互作用(Epigenome × environment；Epi × E)可能构成了一种新的奖励加工机制，目前还缺乏直接证据。我们进行了首次纵向研究，以调查应激相关基因nr3c1的DNA甲基化在多大程度上与儿童虐待、青年奖励反应（RR）以及抑郁（特别是快感缺乏维度）和焦虑症状的下游风险相关。方法：共192名18 ~ 25岁的中国大学生(年龄 = 21.08±1.91岁；59.4%为女性)。奖励积极性（RewP）及其时频成分是通过一个经典的金钱奖励任务引起的。通过颊细胞对NR3C1启动子外显子1F上的胞嘧啶甲基化（NR3C1-1F）进行了测序。儿童虐待自述RR和抑郁、焦虑症状通过问卷进行评估。结果：NR3C1-1F甲基化与儿童虐待在RewP上的相互作用显著，但与δ和θ分量或自报RR无关。在NR3C1-1F甲基化程度较高的个体中，儿童虐待的严重程度和暴露次数与RewP呈负相关，而在NR3C1-1F甲基化程度较低的个体中，与RewP呈正相关，表现出“拟合优度”相互作用。这种相互作用与快感缺乏症维度有关，但与抑郁或焦虑症状的总分无关。结论：目前的研究结果为Epi × E相互作用在奖励加工中的作用提供了初步证据，突出了电生理信号的跨水平分析，并进一步了解了应激诱导的奖励功能和相关症状的生物学基础。然而，鉴于目前样本的高功能特征，这些发现在高风险临床样本中的普遍性应予以谨慎。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

NeuroImage 医学-核医学

CiteScore

11.30

自引率

10.50%

发文量

809

审稿时长

63 days

期刊介绍： NeuroImage, a Journal of Brain Function provides a vehicle for communicating important advances in acquiring, analyzing, and modelling neuroimaging data and in applying these techniques to the study of structure-function and brain-behavior relationships. Though the emphasis is on the macroscopic level of human brain organization, meso-and microscopic neuroimaging across all species will be considered if informative for understanding the aforementioned relationships.