The **hypothalamic-pituitary-adrenal axis** (HPA axis) is the neuroendocrine system that regulates the stress response in mammals. Its basic functioning: in the face of a threat, the hypothalamus releases CRH (corticotropin-releasing hormone), the pituitary responds with ACTH (adrenocorticotropic hormone), and the adrenal glands secrete **cortisol**, which prepares the body to fight or flee.
Under normal conditions, the system is self-regulating: cortisol itself, once in circulation, feeds back to the hypothalamus and pituitary, signaling that the response is already active, and returns to baseline levels within hours. The problem is **chronic dysregulation**: when stress is persistent or trauma is severe, the HPA axis remains altered for years, sometimes for life.
Central findings in transgenerational trauma link FKBP5, glucocorticoid receptor methylation, and HPA axis regulation. Yehuda et al. (2014) documented that offspring of Holocaust survivors with PTSD show specific patterns of cortisol receptor regulation that differ from both controls and their own traumatized parents — a pattern biologically consistent with the transgenerational transmission of trauma.
Understanding the HPA axis allows us to translate clinical experiences (“I feel my body is always on alert,” “I can’t rest”) into verifiable physiological language, and to understand why certain early wounds leave marks that do not respond solely to verbal therapy.
Evidence and contemporary voices
The HPA (hypothalamic-pituitary-adrenal) axis is a key neuroendocrine system in the stress response, activated by the release of CRH from the hypothalamus, which stimulates ACTH in the anterior pituitary and, in turn, cortisol in the adrenals. Its chronic dysregulation is associated with disorders such as depression, anxiety, and PTSD. Rachel Yehuda (Yehuda et al., 2015) demonstrated HPA axis hyperreactivity in 9/11 survivors with PTSD, with elevated diurnal cortisol levels, in longitudinal studies at Mount Sinai Hospital. In transgenerational trauma, Yehuda et al. (2016) found HPA axis hyporeactivity, with smaller hippocampal volume and low cortisol levels, in offspring of Holocaust survivors, suggesting epigenetic transmission via FKBP5 gene methylation. Isabelle Mansuy (Franklin et al., 2010), from ETH Zurich, evidenced in murine models of early maternal stress transgenerational alterations in HPA axis gene expression, reversible with HDAC inhibitors.
Verifiable citations
- "The HPA axis response to stress is dysregulated in PTSD, with elevated evening cortisol levels." — Rachel Yehuda, Post-traumatic stress disorder (2002).
- "Maternal stress alters GR expression in offspring via epigenetic mechanisms in the HPA axis." — Isabelle M. Mansuy, Transgenerational Epigenetic Inheritance (2016).
Researchers and Key Figures
- Rachel Yehuda — Icahn School of Medicine at Mount Sinai — HPA dysregulation in PTSD and transgenerational trauma
- Isabelle M. Mansuy — ETH Zurich — epigenetics of the HPA axis in animal models of stress
- Bruce McEwen — Rockefeller University — neuroplasticity and allostasis of the HPA axis
- Sonja Entringer — University of California, Irvine — fetal programming of the HPA axis
Auditable Sources
Additional research generated by consulting academic sources (Perplexity Sonar Pro). Citations and URLs are the responsibility of their original source; verify before formally citing.
Bibliography
- Influences of maternal and paternal PTSD on epigenetic regulation of the glucocorticoid receptor gene in Holocaust survivor offspring — Rachel Yehuda et al.. American Journal of Psychiatry, 171(8), 872-880, 2014.
- Holocaust Exposure Induced Intergenerational Effects on FKBP5 Methylation — Rachel Yehuda et al.. Biological Psychiatry, 80(5), 372-380, 2016.
- The Body Keeps the Score — Bessel van der Kolk. Eleftheria, 2015.
These books are in the reference library that nourishes Constelando el Origen.
Site articles on this topic
Related terms
Cortisol
The primary human glucocorticoid. A stress hormone released by the adrenal glands. Its baseline and response levels are altered in trauma victims and in children of survivors.
See entryFKBP5 (stress gene)
A gene that regulates the sensitivity of the glucocorticoid receptor to cortisol. Its epigenetic modifications are one of the central findings in the transgenerational transmission of trauma.
See entryEpigenetics
The study of changes in gene expression that do NOT alter the DNA sequence, are heritable, and can be activated by life experiences—including trauma.
See entryTransgenerational trauma
Pain or trauma unprocessed by one generation that is transmitted—psychically, somatically, and, according to recent evidence, epigenetically—to subsequent generations.
See entryInterrupted bonding
An early rupture in the bond between a child and their primary attachment figure—usually the mother—that leaves a deep systemic imprint.
See entryA session that names what hurts
If you recognize this dynamic in your own story, a Family Constellation can reveal its origin and what movement brings order to it. Daniela accompanies each case with respect.
Sessions in Spanish only