Neuroimmune programming of childhood trauma: comorbid mechanisms and developmental origins of depression and autoimmune diseases.

Adverse childhood experiences (ACEs) represent a critical environmental trigger for the adult comorbidity of depression and autoimmune diseases. This review synthesizes evidence showing that ACEs induce persistent dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis and the sympathetic nervous system, thereby promoting a chronic low-grade inflammatory state. This state is characterized by elevated pro-inflammatory cytokines (e.g., IL-6, TNF-α), immune cell dysfunction, and epigenetic modifications. Facilitated by microglial activation and monocyte-mediated disruption of the blood–brain barrier, this pro-inflammatory milieu disrupts central nervous system homeostasis, contributing to the pathogenesis of both depressive symptoms and autoimmune disorders. Aberrant neuroimmune crosstalk emerges as a core mechanism underlying this comorbidity. Future research must delineate developmental windows of vulnerability and the differential effects of adversity types to translate these insights into novel therapeutic strategies targeting the neuroimmune axis—such as anti-cytokine therapies or vagus nerve stimulation—for high-risk populations.