Childhood adversity moderates the association between serum cortisol and earlier-onset posttraumatic stress disorder

BACKGROUND: The role of cortisol in Posttraumatic stress disorder (PTSD) remains controversial due to inconsistent findings. Childhood adversity may recalibrate the hypothalamic-pituitary-adrenal (HPA) axis, altering the prognostic value of cortisol. Furthermore, the biological mechanisms underlying earlier- versus delayed-onset PTSD trajectories may differ. METHODS: A total of 895 patients hospitalized for physical injuries were prospectively followed for 2 years. Baseline serum cortisol levels and childhood adversity were assessed within one month of injury. PTSD diagnoses and onset timing were determined at 3, 6, 12, and 24 months using the Clinician-Administered PTSD Scale for DSM-5. Logistic regression models evaluated individual and interactive effects of cortisol and childhood adversity on PTSD onset, adjusting for relevant covariates. RESULTS: Neither baseline serum cortisol levels nor childhood adversity independently predicted PTSD onset. However, a significant interaction was observed for earlier-onset PTSD, such that lower cortisol levels were associated with increased risk only among individuals without childhood adversity. This interaction was not observed for delayed-onset PTSD. Cortisol levels were not correlated with childhood adversity. CONCLUSION: Baseline cortisol predicts earlier-onset PTSD only in the absence of childhood adversity, suggesting that developmental context modifies the prognostic significance of cortisol. Biological risk stratification for PTSD must consider developmental history and symptom onset timing.