Childhood maltreatment, multilocus HPA-axis genetic variation and adolescent comorbidity profiles of depressive and anxiety symptoms

Despite a growing body of evidence showing both genetic and environmental influences on adolescent depression and anxiety, the involved comorbid mechanisms regarding gene-by-environment (G × E) interaction remain unclear. The current study was the first to investigate the extent to which multilocus hypothalamic-pituitary-adrenal (HPA)-axis genetic variants moderated the association between childhood maltreatment and adolescent comorbid depression and anxiety. The participants were 827 Chinese Han adolescents (Mage = 16.45 ± 1.37 years; 50.2 % girls). A theory-driven multilocus genetic profile score (MGPS) was computed by calculating alleles of core HPA-axis genes (CRHR1, NR3C1, NR3C2, and FKBP5) associated with heightened stress reactivity. Childhood maltreatment was retrospectively collected using Childhood Trauma Questionnaire. Comorbidity profiles of self-reported adolescent depressive and anxiety symptoms were constructed via person-centered latent profile analysis. Three heterogeneous comorbidity profiles of depressive and anxiety symptoms were identified: comorbid severe symptoms (9.7 %), comorbid moderate symptoms (46.4 %) and comorbid mild symptoms (43.9 %). The HPA-axis related MGPS significantly interacted with childhood maltreatment, especially emotional maltreatment (emotional abuse: OR = 1.14, 95 % CI [1.03, 1.26], p < .01; emotional neglect: OR = 1.07, 95 % CI [1.01, 1.13], p < .05), to distinguish the comorbid severe symptoms profile from the comorbid mild symptoms profile (OR = 1.03, 95 % CI [1.01, 1.06], p < .05). The HPA-axis related genes showed an additive polygenic sensitivity toward childhood maltreatment, which might be one of the polygenic G × E mechanisms underlying adolescent comorbid depression and anxiety.