Cortisol regulation in posttraumatic stress disorder and major depression: a chronobiological analysis.

The aim of the present study was to evaluate the pattern of basal cortisol release in PTSD and major depression using a chronobiological analysis. Plasma for cortisol determination was obtained from 15 combat veterans with PTSD, 14 subjects with major depression, and 15 normal men every 30 min during a 24-hour period of bed rest. Raw cortisol data were modeled using standard and multioscillator cosinor models to determine the best fitting functions for circadian, hemicircadian, and ultradian components of cortisol release. PTSD subjects had substantially lower cortisol levels, and displayed a pattern of cortisol release that was better modeled by circadian rhythm. PTSD subjects also showed a greater circadian signal-to-noise ratio than the other groups. In contrast, depressed patients displayed a less-rhythmic, more chaotic pattern of cortisol release. The pattern of cortisol secretion and regulation observed in the PTSD group under baseline conditions may reflect an exaggerated sensitization, whereas the chronobiological alterations in depression may reflect dysregulation, of the hypothalamic-pituitary-adrenal (HPA) axis.

Plasma norepinephrine and 3-methoxy-4-hydroxyphenylglycol concentrations and severity of depression in combat posttraumatic stress disorder and major depressive disorder.

BACKGROUND: Catecholamines are thought to play a significant role in the pathophysiology of posttraumatic stress disorder (PTSD), but findings in PTSD have been discrepant. METHODS: To obtain more information about catecholamine activity in PTSD, we sampled plasma norepinephrine (NE) and 3-methoxy-4-hydroxyphenylglycol (MHPG) concentrations over a 24-hour period in men with PTSD (n = 15) and major depressive disorder (MDD) (n = 12), and nonpsychiatric comparison subjects (n = 13), under unstimulated conditions. Chronobiological analyses were performed to determine possible changes in the circadian and ultradian release of these hormones. RESULTS: Significant group differences were present for mean plasma NE levels (p = .03), but not MHPG. NE levels were significantly associated with severity of depression in the PTSD group (p = .002). Therefore, PTSD subjects were further subdivided into those with and without a comorbid secondary depression. Increased NE levels were only present in PTSD subjects who did not have a secondary depression. This study also found no significant group differences on any of the chronobiological parameters. CONCLUSIONS: The results clarify that increased NE levels in PTSD may be confined to the subgroup of subjects who do not have comorbid depression, and as such, may help resolve some of the discrepancies in the literature regarding basal catecholamine activity.

Learning and memory in combat veterans with posttraumatic stress disorder.

OBJECTIVE: The authors investigated a broad range of memory functions for stimuli unrelated to trauma to determine whether symptoms such as intrusive memories might reflect an underlying cognitive deficit unrelated to the psychological content of the traumatic memory in patients with posttraumatic stress disorder (PTSD). METHOD: The authors measured the intellectual functioning of 20 male combat veterans with PTSD and 12 normal comparison subjects using the WAIS and evaluated them for performance on memory using the California Verbal Learning Test. RESULTS: Veterans with PTSD showed normal abilities in the functions of initial attention, immediate memory, cumulative learning, and active interference from previous learning. However, these veterans showed a circumscribed cognitive deficit, manifested by the presence of substantial retroactive interference and revealed by a significant decrement in retention following exposure to an intervening word list. CONCLUSIONS: The data suggest that patients with PTSD may have fairly specific deficits in the monitoring and regulation of memory information.

Increased pituitary activation following metyrapone administration in post-traumatic stress disorder.

Our previous findings have demonstrated that individuals with post-traumatic stress disorder (PTSD) show lower basal cortisol levels, a larger number of lymphocyte glucocorticoid receptors, and an enhanced suppression of cortisol following the administration of dexamethasone compared to normals and patients with major depression. We have previously suggested that these alterations reflect an enhanced negative feedback inhibition of the hypothalamic-pituitary-adrenal (HPA) axis in PTSD. However, in the absence of direct knowledge of pituitary capability in this disorder, it has been equally likely that the alterations observed reflected either pituitary or adrenal insufficiency. In the present study, we examined ACTH release from the pituitary gland in PTSD following the administration of metyrapone. Metyrapone resulted in a significantly greater increase of ACTH and 11-deoxycortisol in combat veterans with PTSD (n = 11) compared with normal male volunteers (n = 8). When seen in the context of other abnormalities observed in PTSD, the present demonstration of increased pituitary activity in the absence of negative feedback provides unequivocal support for the hypothesis of enhanced negative feedback.