Peer-reviewed article

Interactive effect of childhood adversity and HPA-axis multilocus genetic variation on alexithymia in adolescents.

Hongjia Zhou, Wei Lü · 7 Oct 2026

Abstract

BACKGROUND: Childhood adversity increases risk for affective symptoms, including alexithymia, a transdiagnostic emotion-processing difficulty common in adolescence. Hypothalamic-pituitary-adrenal (HPA) axis-related genetic variation may contribute to individual differences in sensitivity to adverse environments. This study examined whether an HPA-axis-related multilocus genetic profile score (MGPS) moderated the association between childhood adversity and adolescent alexithymia. METHODS: The present study addressed this issue in a sample of 460 adolescents (Mage = 12.73, SD = 0.72; 54.1% female) who completed the Childhood Trauma Questionnaire and the Toronto Alexithymia Scale. Saliva samples were collected for deoxyribonucleic acid (DNA) genotyping, and an HPA-axis-related multilocus genetic profile score (MGPS) was constructed from six candidate polymorphisms. Hierarchical regression and re-parameterized regression analyses were conducted. RESULTS: Childhood adversity was positively associated with alexithymia. HPA-axis MGPS moderated this association. Specifically, adolescents with high HPA-axis MGPS exhibited higher levels of alexithymia when exposed to high childhood adversity but lower levels when exposed to low childhood adversity, providing preliminary support for the differential susceptibility model. LIMITATIONS: The cross-sectional design precludes causal inference, and the findings require replication in longitudinal, clinically enriched, and more diverse samples. CONCLUSIONS: HPA-axis multilocus genetic variation may function as a biological sensitivity factor in the association between childhood adversity and adolescent alexithymia. These findings extend gene-environment interaction research to alexithymia and highlight individual differences in adolescents' emotional responses to adversity.