Glucocorticoid receptor gene exon 1F methylation moderates concurrent but not longitudinal associations between caregiver parenting and child behavior problems in a manner consistent with differential susceptibility

Methylation alterations of the glucocorticoid receptor gene (<i>NR3C1</i>) may help explain why not all individuals experiencing insensitive parenting develop behavior problems, yet evidence from human cohorts remains limited. This longitudinal study examined associations among <i>NR3C1</i> methylation, caregiver parenting, and child internalizing and externalizing behaviors. A total of 224 Han Chinese preschoolers <i>(M</i>_age = 47.33 ± 9.60 months; 42.5% girls) were recruited from Jinan, China, in 2021 (T1). Parenting quality and child behavior problems were reported by both parents, and <i>NR3C1</i> methylation across 46 cytosine-phosphate-guanine sites in the exon 1F promoter region was sequenced from buccal cells. Follow-up assessments were conducted 1.5 years later among 113 children who stayed in the same kindergarten (<i>M</i>_age = 63.60 ± 7.68 months; 45.7% girls). <i>NR3C1</i> methylation at baseline moderated the association between parenting and baseline, but not follow-up, behavior problems, consistent with differential susceptibility. Children with lower methylation exhibited more behavior problems under low-quality parenting but fewer under high-quality parenting. This interaction did not vary between parental and child sex, or <i>NR3C1 Bcl</i>I (rs41423247) and <i>Tth111</i>I (rs10052957) polymorphisms. Findings highlight the dynamic nature of Epigenome × Environment interactions and suggest that lower <i>NR3C1</i> methylation may act as a plasticity factor in preschool children.