The adrenal is doing what it’s supposed to do, you just don't understand it

Exposure to early life adversity is thought to induce long-term alterations in the hypothalamic-pituitary-adrenal (HPA) axis activity and regulation, particularly when such experiences occur during periods of rapid neurodevelopment in early childhood. Although this hypothesis is well supported in animal research, evidence in humans remains comparatively limited and less well understood. The present review synthesizes current evidence on the immediate and long-term impact of adversity experienced roughly in the first 5 years of life, focusing on two forms of severe adverse caregiving: early institutional care and child maltreatment. Across studies, children exposed to early adverse care show persistent alterations in HPA axis activity under both basal and stress-related conditions, extending from infancy to adulthood. We examine how the developmental timing, duration and severity of exposure, as well as the caregiving context, affect these outcomes, and highlight emerging evidence of potential recalibration of the HPA axis during puberty following marked changes (for good or bad) in caregiving quality. We conclude by outlining the implications of this body of work for understanding the programming effects of early adversity and by identifying key methodological limitations and priorities for future research. In particular, longitudinal designs with repeated assessments, combined with integrative multisystem resilience-oriented approaches, are essential. This should be integrated with and neurobiological grounded by, mechanistic animal studies. Together, these efforts will help elucidate how and when early adversity becomes biologically embedded across child development.