HPA-axis multilocus genetic variation moderates longitudinal link between friendship quality and adolescent depressive symptoms after childhood abuse.

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 (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.

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 × 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.

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.