Child abuse & neglect · 2025
HPA-axis multilocus genetic variation moderates longitudinal link between friendship quality and adolescent depressive symptoms after childhood abuse.
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Zhao Xian, Chang Mengmeng, Zeng Zihao, Hu Yiqiu
Аннотация
BACKGROUND: 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.
OBJECTIVE: 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.
METHOD: A total of 931 adolescents (Mage = 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.
RESULTS: 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 × E1 × E2), 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.
CONCLUSIONS: 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.
OBJECTIVE: 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.
METHOD: A total of 931 adolescents (Mage = 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.
RESULTS: 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 × E1 × E2), 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.
CONCLUSIONS: 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.