Adolescent depression, childhood maltreatment, and the immune system; a role for epigenetic aging?

Background: Childhood maltreatment is a major risk factor for the development of depression, as well as for imbalances in the immune system, including chronic low-grade inflammation. Less is known about potential immune imbalances in adolescent depression and the role of childhood maltreatment. Furthermore, accelerated epigenetic aging may contribute to the development of inflammation, but has never been examined in the context of adolescent depression. Methods: We investigated childhood maltreatment, inflammation, and epigenetic aging in 78 healthy adolescents and 33 adolescents with a clinically diagnosed depressive disorder. Childhood maltreatment was assessed via self-report, and inflammatory markers (CRP, IL-1β, IL-6, IL-8, sIgA, and TNF-α) were analyzed in saliva. DNA methylation was analyzed in a subsample (n = 48) of both healthy and unmedicated, depressed adolescents to estimate epigenetic age (Horvath and PedBE clocks). Results: The MANOVA showed that depression was significantly associated with the immune markers, but not with epigenetic aging. Post-hoc tests suggested however that IL-8 levels were reduced, while none of the other markers were affected. Unexpectedly, childhood (emotional) maltreatment was significantly associated with epigenetic age deceleration on the PedBE clock (p = .01), and not with inflammation. The inflammatory markers were not associated with either of the epigenetic age clocks. Conclusions: Our results contrast with previous literature in adults, indicating that epigenetic age acceleration and inflammation are not unequivocal indicators of depression and childhood trauma in adolescents. Future studies with larger, more heterogeneous samples should investigate under which circumstances increased or decreased levels of these biological markers indicate vulnerability for health-related outcomes. Better understanding of these mechanisms in adolescence may help to develop appropriate interventions supporting a healthy development of children who experienced maltreatment or depression.