Zhao Xian, Chang Mengmeng, Zeng Zihao, Hu Yiqiu
School of Educational Science, Hunan Normal University, Changsha 410081, Hunan Province, China.
School of Educational Science, Hunan Normal University, Changsha 410081, Hunan Province, China; China Research Center for Mental Health Education of Hunan Province, Hunan Normal University, Changsha 410081, Hunan Province, China.
Child Abuse Negl. 2025 Aug 13;169(Pt 1):107635. doi: 10.1016/j.chiabu.2025.107635.
Studies indicate that genetic variations associated with the functioning of the hypothalamic-pituitary-adrenal (HPA) axis can influence the relationship between environmental stressors and depressive symptoms, but examining gene-environment interactions with single polymorphisms limits power.
This study examined a multilocus genetic profile score (MGPS) for HPA-axis function and investigated its interaction with childhood abuse, friendship quality, and the longitudinal trajectory of depressive symptoms among adolescents.
A total of 931 adolescents (M = 14.21, 54.6 % girls) were assessed at baseline and followed across three additional waves at six-month intervals over two years. Additive MGPS were calculated using six single nucleotide polymorphisms within HPA-axis genes (NR3C1, NR3C2, SKA2, FKBP5). For the final analysis, 483 participants were included based on reported childhood abuse (score ≥ 1) and valid genetic data.
Latent growth modeling revealed upward trajectories in both friendship quality and depressive symptoms. The latent growth interaction model revealed a significant three-way interaction (G × E × E), where higher HPA-axis multilocus genetic variation risk scores strengthened the interaction between childhood abuse and friendship quality in predicting depressive symptoms trajectories. Specifically, under high HPA-axis multilocus genetic variation risk scores and childhood abuse, a higher increase in friendship quality predicted a decline in depressive symptoms, while lower friendship growth predicted an increase, consistent with the differential susceptibility model.
These findings suggest that enhancing friendship quality may buffer against depressive symptom escalation among adolescents with heightened genetic and environmental vulnerabilities. Targeting peer relationships could serve as a promising direction for early intervention efforts.
