Posttraumatic stress disorder in children and adolescents: neuroendocrine perspectives

Posttraumatic stress disorder (PTSD) is a syndrome of distress that develops after exposure to traumatic life experiences. Dysregulation of both the hypothalamic-pituitary-adrenal (HPA) axis and the locus caeruleus/norepinephrine-sympathetic nervous system (LC/NE-SNS) is associated with the pathophysiology of the disorder. Studies have demonstrated a neuroendocrine profile unique to adults with PTSD, with centrally elevated corticotropin-releasing hormone (CRH), low cortisol in the periphery, and elevated catecholamines. Traumatic stress experiences in early life are strong predisposing factors for later PTSD development. In addition, early life stress programs the developing brain to overreact to future stressors. In children and adolescents involved in motor vehicle accidents, we found that high evening salivary cortisol and morning serum interleukin 6 concentrations were predictive of PTSD development 6 months later. We demonstrated a progressive divergence of the HPA and LC/NE-SNS axes of the stress system, which may be part of the pathophysiologic mechanism responsible for PTSD maintenance. An initial elevation of cortisol in the aftermath of the trauma, followed by a gradual normalization and finally low cortisol secretion, together with a gradual elevation of catecholamines over time, may represent the natural history of neuroendocrine changes in pediatric PTSD. Thus, the low cortisol concentrations found in adults with PTSD may reflect prior trauma and might represent a biologic vulnerability factor for later PTSD development.