Glucocorticoid receptor gene (NR3C1) methylation, childhood maltreatment, multilevel reward responsiveness and depressive and anxiety symptoms: A neuroimaging epigenetic study
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-r...
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Elsevier
2025-02-01
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| author | Yajing Xu Shan Yang Cong Cao |
| author_facet | Yajing Xu Shan Yang Cong Cao |
| author_sort | Yajing Xu |
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| description | 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 (Mage = 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. |
| format | Article |
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| institution | Kabale University |
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| language | English |
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| publisher | Elsevier |
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| spelling | doaj-art-c0efa21dd740435090c798094d48df362025-01-23T05:26:21ZengElsevierNeuroImage1095-95722025-02-01306121003Glucocorticoid receptor gene (NR3C1) methylation, childhood maltreatment, multilevel reward responsiveness and depressive and anxiety symptoms: A neuroimaging epigenetic studyYajing Xu0Shan Yang1Cong Cao2School of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong University, Jinan, PR ChinaSchool of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong University, Jinan, PR ChinaCorresponding author: School of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong University, No. 44 West Wenhua Road, Jinan 250012, Shandong Province, PR China.; School of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong University, Jinan, PR ChinaBackground: 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 (Mage = 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.http://www.sciencedirect.com/science/article/pii/S1053811925000035Neuroimaging epigeneticsEvent-related potentialNR3C1 methylationReward responsivenessGoodness-of-fitChildhood maltreatment |
| spellingShingle | Yajing Xu Shan Yang Cong Cao Glucocorticoid receptor gene (NR3C1) methylation, childhood maltreatment, multilevel reward responsiveness and depressive and anxiety symptoms: A neuroimaging epigenetic study NeuroImage Neuroimaging epigenetics Event-related potential NR3C1 methylation Reward responsiveness Goodness-of-fit Childhood maltreatment |
| title | Glucocorticoid receptor gene (NR3C1) methylation, childhood maltreatment, multilevel reward responsiveness and depressive and anxiety symptoms: A neuroimaging epigenetic study |
| title_full | Glucocorticoid receptor gene (NR3C1) methylation, childhood maltreatment, multilevel reward responsiveness and depressive and anxiety symptoms: A neuroimaging epigenetic study |
| title_fullStr | Glucocorticoid receptor gene (NR3C1) methylation, childhood maltreatment, multilevel reward responsiveness and depressive and anxiety symptoms: A neuroimaging epigenetic study |
| title_full_unstemmed | Glucocorticoid receptor gene (NR3C1) methylation, childhood maltreatment, multilevel reward responsiveness and depressive and anxiety symptoms: A neuroimaging epigenetic study |
| title_short | Glucocorticoid receptor gene (NR3C1) methylation, childhood maltreatment, multilevel reward responsiveness and depressive and anxiety symptoms: A neuroimaging epigenetic study |
| title_sort | glucocorticoid receptor gene nr3c1 methylation childhood maltreatment multilevel reward responsiveness and depressive and anxiety symptoms a neuroimaging epigenetic study |
| topic | Neuroimaging epigenetics Event-related potential NR3C1 methylation Reward responsiveness Goodness-of-fit Childhood maltreatment |
| url | http://www.sciencedirect.com/science/article/pii/S1053811925000035 |
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