Developmental psychoneuroendocrine and psychoneuroimmune pathways from childhood adversity to disease

•Physical trauma, disrupted caregiving, & unpredictability have unique developmental implications.•RSD may be a useful animal analog for childhood adversity involving physical trauma.•Maternal separation may be useful for understanding disrupted caregiving.•CVS may be useful for understanding living in an unpredictable developmental environment.•Infancy and pubertal may be sensitive periods for childhood adversity exposure.

Childhood adversity has been repeatedly and robustly linked to physical and mental illness across the lifespan. Yet, the biological pathways through which this occurs remain unclear. Functioning of the inflammatory arm of the immune system and the hypothalamic-pituitary-adrenal (HPA)-axis are both hypothesized pathways through which childhood adversity leads to disease. This review provides a novel developmental framework for examining the role of adversity type and timing in inflammatory and HPA-axis functioning. In particular, we identify elements of childhood adversity that are salient to the developing organism: physical threat, disrupted caregiving, and unpredictable environmental conditions. We propose that existing, well-characterized animal models may be useful in differentiating the effects of these adversity elements and review both the animal and human literature that supports these ideas. To support these hypotheses, we also provide a detailed description of the development and structure of both the HPA-axis and the inflammatory arm of the immune system, as well as recent methodological advances in their measurement. Recommendations for future basic, developmental, translational, and clinical research are discussed.