Independent, Multiplicative, and Cumulative Effects of Recent Stressful Life Events and Adverse Childhood Events on Depressive Symptoms among College Students: Moderation by the HPA-axis Multilocus Genetic Variation.

Previous research has explored the effects of early and recent stress on depressive symptoms, yielding meaningful findings. However, no research has yet comprehensively verified and compared the independent, multiplicative (interactive), and cumulative (additive) effects of these stresses on depressive symptoms. Consequently, the mechanisms by which early and recent stress contribute to depressive symptoms, as well as the extent of individual differences in these processes, remain poorly understood. This study aimed to address this gap by simultaneously examining the independent, multiplicative, and cumulative effects of recent stressful life events and adverse childhood events on depressive symptoms in late adolescence. Additionally, it investigated the moderating role of multilocus genetic variations related to the hypothalamic-pituitary-adrenal (HPA) axis within these models. A theory-driven multilocus genetic profile score (MGPS) was calculated using FKBP5 rs1360780, NR3C1 rs41423247, and CRHR1 rs110402 polymorphisms. The study recruited a sample of 1227 adolescents (M = 18.94 ± 0.70 years, 56.8% girls) from one vocational college, two general colleges and two universities. Results showed that both the independent and cumulative effects of recent stressful life events and adverse childhood events on depressive symptoms were significant, while the multiplicative effects were non-significant. Moreover, the independent effects model was more explanatory than the cumulative effects model, with recent stressful life events being the primary contributor. A significant moderating effect of MGPS on the association between recent stressful life events and depressive symptoms was also observed. Specifically, those with higher MGPS, i.e., with higher susceptibility, exhibited more depressive symptoms when exposed to higher levels of recent stressful life events but fewer symptoms when exposed to lower levels. These findings deepen the understanding of how early and recent stress, along with genetic factors, influence depressive symptoms. It also provides valuable insights for targeted interventions to reduce depressive symptoms among college students.