Pro-inflammatory Cytokines, Childhood Trauma, and Neuropsychological Function in Adolescent Depression

Pro-inflammatory cytokines have been linked to early childhood trauma and adversity, depression, and impairment in executive function and memory in adults. Whether these links are present during adolescence, a critical period of brain development, a point more proximal to childhood trauma, and when vulnerability to depression is heightened, is not well understood. Serum levels of interleukin (IL)-6, IL-1β, and tumor necrosis factor alpha (TNF-α) were measured in 71 un-medicated adolescents aged 12-17, including 40 with any mood disorder (AMD), a sub-set (n = 22) of whom reported a history of childhood trauma (AMD-T), and 31 healthy controls (HCs). Participants completed a neuropsychological assessment battery and the Children’s Depression Rating Scale, which were analyzed separately into dimensions of neuropsychological function and depression. IL-6 was elevated in AMD and AMD-T adolescents compared to controls and TNF-α was elevated in AMD participants only, whereas no group differences were found in IL-1β. Additionally, inflammation markers alone were associated with depressed mood and memory dysfunction in adolescents (IL-6), whereas inflammation markers interacted in at-risk, depressed and trauma-exposed teens, to predict somatic complaints (TNF-α) and executive function (IL-1β). The current results suggest that inflammation probes may contribute to early identification of risk for depression and neuropsychological dysfunction. This study also confers initial evidence for cytokine-specific patterns of mood disruption and cognitive dysfunction in adolescence, early in the course of illness.