Early life adversity influences brain development through neuroendocrine, immune, and microbiota-related mechanisms: A review

The early life experiences have an important impact on the development of the brain and behavior and early life adversities (ELA) may affect several biological systems including the hypothalamic-pituitary-adrenal (HPA) axis, neurotransmitter and immune signaling systems, and microbiota composition. Dysregulation of these systems may result in an altered stress reactivity in both early life and the adulthood periods leading to maladaptive responses to the environmental stimuli. The activation of certain neuropeptides, including oxytocin, stimulation of the HPA axis, and increased glucocorticoid levels, may also play an important role in the early adaptive processes. In terms of brain maturation, ELA can directly or indirectly elicit structural changes in neurite growth, neurogenesis, neuronal connectivities, and signaling processes, which may contribute to the production of the long-term behavioral changes associated with an increased risk of the neuropsychiatric disorders’ development in later periods of the life. In this review, we summarize the effect of ELA on the HPA axis function, stress-related hormonal balance, immune responses, and the gut microbiome indicating how these changes may affect the brain function and behavior in the early stages of the life and adulthood. We also provide insight into animal studies revealing the responses of corticotropin-releasing hormone, urocortins, and corticosterone in various neural circuits in response to ELA evoked by maternal separation and limited bedding paradigms.