BioProject

Exposure to serious or traumatic events early in life can lead to persistent alterations in physiological stress response systems, including enhanced cross-talk between the neuroendocrine and immune system. More...

Exposure to serious or traumatic events early in life can lead to persistent alterations in physiological stress response systems, including enhanced cross-talk between the neuroendocrine and immune system. These programming effects may be mechanistically involved in mediating the effects of adverse childhood experience on disease risk in adulthood. Here, we investigated neuroendocrine as well as genome-wide mRNA expression responses in monocytes to acute stress exposure, in a sample of healthy adults (n=30) with a history of early childhood adversity, and a control group (n=30) without trauma experience. The early adversity group showed altered hypothalamus-pituitary-adrenal (HPA) axis responses to stress, evidenced by lower ACTH and cortisol responses. Analyses of gene expression patterns showed a larger stress-induced increase of cardinal pro-inflammatory transcripts IL6 and FOSB, and an increased activity of pro-inflammatory upstream signaling in the early adversity group. We also identified transcripts that were differentially correlated with stress-induced cortisol increases between the groups. Noteworthy, FKBP5 expression was less responsive to cortisol induction in the early adversity group, with potential effects on the ultra-short feedback loop that balances FKBP5 and glucocorticoid receptor activity. Further exploratory analyses showed differential stress-induced regulation of gene transcription between the groups. Prominent among the differentially regulated transcripts were those coding for genes involved in signal transducer activity, G-protein coupled receptors, and several genes involved in serotonin receptor signaling. We suggest that childhood adversity leads to persistent alterations in transcriptional control of stress responsive pathways, which - when chronically or repeatedly activated - might predispose individuals to stress-related psychopathology. Overall design: 180 samples were analyzed. 60 healthy adults (30 with history of childhood adversiy, 30 controls without trauma history) were subjected to a standardized laboratory stress protocol. Blood samples for the isolation of CD14+ monocytes were taken at 45 before, and at 45 and 180 minutes post stress. Less...