Yehuda (2002) in Biological Psychiatry investigated biological characteristics of post-traumatic stress disorder (PTSD), with an emphasis on the regulation of the stress hormone cortisol and the hypothalamic-pituitary-adrenal axis (HPA axis). Rachel Yehuda and colleagues studied people with PTSD—often following war experiences or other severe traumas—and compared their hormonal profiles with those of control subjects.

A central finding was that PTSD is not simply associated with elevated cortisol, as had long been assumed. On the contrary: many people with chronic PTSD actually exhibit lower basal cortisol levels, but an increased sensitivity of the stress axis to negative feedback. Using dexamethasone suppression tests, the researchers showed that the HPA axis in PTSD often responds more strongly to inhibitory signals. This points to a dysregulated system: the stress response is activated quickly but also abnormally inhibited, which can contribute to hyperalertness, flashbacks, and difficulty recovering from stress.

The study also discusses intergenerational and early-life influences. Trauma, especially early in life, can cause lasting changes in stress regulation. These changes influence how an individual responds to stress later in life and can increase vulnerability to PTSD. Yehuda emphasizes that biological markers such as cortisol patterns are not simple diagnostic tools, but they do provide insight into the physiology of trauma.

The broader conclusion is that PTSD is associated with specific neuroendocrine patterns rather than a general “overactivation” of stress hormones. This refines the understanding of trauma: it involves a complex dysregulation of stress systems, with implications for treatment, prevention, and research into how trauma is permanently embedded in the body and brain.