According to this model, individuals with PTSD experience chronic and recurrent stress events that lead to increased secretion

of CRH. Pituitary sensitivity to CRH decreases the need to compensate for increased CRH release, as reflected by blunted ACTH responses to CRH infusion. To protect against the toxic effects of elevated Cortisol, the HPA axis in PTSD becomes increasingly sensitized to Inhibitors,research,lifescience,medical feedback inhibition from Cortisol through upregulation of glucocorticoid receptors and other mechanisms. This is evidenced by low baseline ACTH and Cortisol levels and robust suppression of ACTH and Cortisol release after dexamethasone administration. By tightly controlling Cortisol secretion and responding aggressively

to acute rises in Cortisol levels, the neuroendocrine system may serve to buffer vulnerable neuronal structures such as the hippocampus from cellular toxicity induced by elevated scrum Cortisol levels.54,55 Neuroanatomic changes in PTSD While evidence that severe stress Inhibitors,research,lifescience,medical can affect noradrenergic and neuroendocrine function has been well-established, recent animal studies have identified important neurotic effects of stress-mediated increases in glucocorticoid levels. One neuroanatomical structure Inhibitors,research,lifescience,medical that appears to be particularly susceptible to stress-induced damage is the hippocampus, which is involved in learning and memory circuits. Studies of monkeys exposed to the stressors of disrupted attachment found damage to cells in the hippocampal region56; similar patterns of cell damage

could Inhibitors,research,lifescience,medical be induced by implanting glucocorticoids directly into the hippocampus.57 This suggests that elevated glucocorticoid levels, such as might occur acutely during exposure to traumatic stress, could lead to hippocampal damage. Other studies examining stress-induced hippocampal damage in mice have identified important Inhibitors,research,lifescience,medical memory deficits that are correlated with the extent of hippocampal damage,58 suggesting that structural damage to the hippocampus may also be associated with functional memory deficits. These findings have led investigators to hypothesize that PTSD may be associated with hippocampal changes resulting from either the acute neurotoxic effects of elevated scrum Cortisol during exposure to traumatic stress or the gradual deterioration resulting from Romidepsin mouse glucocorticoid-mediated effects check of chronic stress. Using magnetic resonance imaging (MRI) techniques to measure hippocampal volume, Brcmner et al59 compared hippocampal size in 26 male Vietnam combat veterans with PTSD and 22 healthy controls, and found a statistically significant 8 % reduction in right hippocampal volume in the PTSD group. However, this difference was not associated with PTSD symptoms or combat exposure. Gurvits and colleagues60 compared hippocampal volumes in veterans with PTSD (n=7) and matched controls (n=7).