Adverse childhood experiences, depressive symptoms, and non-suicidal self-injury in Chinese adolescents: the moderating role of SKA2 gene rs7208505 polymorphism

The Hypothalamic-pituitary-adrenal axis (HPA) and its single nucleotide polymorphisms (SNPs) potentially influence depressive symptoms and non-suicidal self-injury (NSSI) among adolescents. Adverse childhood experiences (ACEs) may dysregulate HPA axis functioning, with these complex gene-environment interactions showing significant heterogeneity across individuals. This study examined whether depressive symptoms mediate the relationship between ACEs and adolescent NSSI, and whether HPA axis genetic polymorphisms moderate this indirect pathway. For this study, 172 adolescents aged 12 to 18 years were recruited from Xuzhou Oriental Hospital affiliated with Xuzhou Medical University as the NSSI group. Additionally, 58 age-, sex-, residence-, and health-matched volunteers were recruited from the local area as the healthy control group. Demographic information was collected through questionnaires, and adverse childhood experiences, depressive symptoms, and non-suicidal self-injury behaviors were assessed using the Adverse Childhood Experiences Scale (ACEs Scale), the Beck Depression Inventory-II (BDI-II), and the Non-Suicidal Self-Injury Behavior Scale (NSSI-BS). Blood samples were collected for HPA axis genotyping targeting the following loci: SKA2 (rs7208505, rs9911583), SLC1A3 (rs2269272), FKBP5 (rs9470080), and AVPR1B (rs28373064), which were analyzed using TaqMan-PCR. All statistical analyses were performed in SPSS 27.0, including Hardy-Weinberg equilibrium (HWE), χ² test, and Pearson’s correlation coefficient, as well as PROCESS macro-model mediation analysis and simple slope analysis. Depressive symptoms were found to mediate the association between ACEs and NSSI. The SKA2-rs7208505 polymorphism significantly moderated the relationship between ACEs and depressive symptoms, influencing the indirect pathway from ACEs to depressive symptoms to NSSI. Adolescents with the AA genotype of the SKA2-rs7208505 polymorphism were more susceptible to ACEs and more likely to develop depressive symptoms compared to those with GA and GG genotypes. Timely identification and interventions targeting depressive symptoms, especially among individuals with AA genotypes of SKA2-rs7208505 who have experienced ACEs, may be crucial for preventing or reducing the risk of NSSI in adolescents.