Faculty Bibliography

An increased cortisol response to challenge is associated with a variety of age-related disorders such as Alzheimer's disease, depression, diabetes, metabolic syndrome, and hypertension. Among the healthy elderly, an increased cortisol response to challenge may be a risk factor for developing these age-related disorders. We searched Pubmed, Embase, PsychInfo, Biosis, and Digital Dissertations (January 1966-June 2003) and included 45 parallel-group (young vs. old subjects) studies that used either a pharmacological or psychological challenge in healthy volunteers and measured cortisol response to challenge. We calculated effect sizes (Cohen's d) for the standardized mean differences between groups. Compared to younger controls (n=670, mean age 28 years +/-5), older subjects (n=625, 69+/-6) showed a larger cortisol response to challenge defined as stronger response to stimulation or less inhibition after a suppression test (d=0.42, 95% confidence interval (CI), 0.26-0.57). The effect of age on cortisol release was significantly stronger in women (d=0.65, 95% CI 0.34-0.97) than men (d=0.24, 95% CI 0.02-0.47). Our results demonstrate that aging increases the cortisol response to challenge. This effect of age on cortisol response is almost three-fold stronger in women than men. Prospective studies should explore whether the higher cortisol response in the elderly is a risk factor for developing neuropsychiatric and medical disorders

BACKGROUND: Childhood trauma is a risk factor for anxiety disorders in adulthood. One possible mechanism for this association is an increased neuroendocrine response to stress in adults with a history of childhood trauma. METHODS: In a cross-sectional study, 76 police academy recruits (mean [+/-SD] age 28 +/- 5 years, 10 female) were exposed to a video depicting real-life officers exposed to highly stressful incidents. Salivary cortisol and 3-methoxy-4-hydroxy-phenylglycol (MHPG, the major metabolite of norepinephrine) were collected at baseline, immediately after the video, and 20 min after the video. Childhood trauma before age 14 was assessed with an interview (Life Stressor Checklist-Revised). RESULTS: Exposure to the video elicited significant MHPG and cortisol responses in both groups. Recruits with childhood trauma histories (n = 16) had a significantly greater MHPG response, as evidenced by a group effect (F = 8.0, p < .01), and a group x time interaction (F = 4.1, p < .05). The cortisol response did not differ between groups. CONCLUSIONS: Police academy recruits with childhood trauma histories have an increased catecholamine response to psychological stress. This might serve as a risk factor for anxiety disorders in recruits, and these findings might generalize to other groups with a history of childhood trauma

Alterations of the hypothalamic-pituitary-adrenal (HPA) axis and sleep disturbances have been described separately in post-traumatic stress disorder (PTSD). It is not known if HPA alterations and sleep disturbances are associated in PTSD. This study examined sleep and HPA activity in 20 male medication-free subjects with PTSD and 16 matched healthy controls. Two nights of polysomnography were obtained and 24-h urinary cortisol was collected during day 2. Subjects self-administered a low-dose (0.5 mg) salivary dexamethasone test at home. Compared with controls, PTSD subjects had higher 24-h urinary microg cortisol/g creatinine (mean+/-SD 40+/-17 vs 28+/-12, p=0.03) but not significantly higher 24-h urinary cortisol (mean+/-SD 52+/-15 microg/day vs 43+/-23, p=0.19). PTSD subjects showed a trend towards less cortisol suppression after dexamethasone (73%+/-18 vs 83%+/-10, p=0.06). In the combined sample, delta sleep was significantly and negatively correlated with 24-h urinary cortisol (r=-0.36, p=0.04), and with 24-h urinary cortisol/g creatinine on a trend level (r=-0.34, p=0.06). Our results suggest that increased cortisol is negatively associated with delta sleep. This may contribute to sleep abnormalities in conditions associated with elevated cortisol, possibly including PTSD. Future studies should explore the temporal relationship between HPA activity, sleep disturbances, and psychopathology after a traumatic event

BACKGROUND: Dance and yoga have been shown to produce improvements in psychological well-being. PURPOSE: The aim of this study was to examine some of the psychological and neuroendocrine response to these activities. METHODS: Sixty-nine healthy college students participated in one of three 90-min classes: African dance (n = 21), Hatha yoga (n= 18), or a biology lecture as a control session (n = 30). Before and after each condition participants completed the Perceived Stress Scale (PSS), completed the Positive Affect and Negative Affect Schedule, and provided a saliva sample for cortisol. RESULTS: There were significant reductions in PSS and negative affect (ps < .0001) and Time x Treatment interactions (ps < .0001) such that African dance and Hatha yoga showed significant declines, whereas there was no significant change in biology lecture. There was no significant main effect for positive affect (p = .53), however there was a significant interaction effect (p < .001) such that positive affect increased in African dance, decreased in biology lecture, and did not change significantly in Hatha yoga. There was a significant main effect for salivary cortisol (p < .05) and a significant interaction effect (p < .0001) such that cortisol increased in African dance, decreased in Hatha yoga, and did not change in biology. Changes in cortisol were not significantly related to changes in psychological variables across treatments. There was 1 significant interaction effect (p = .04) such that change in positive affect and change in cortisol were negatively correlated in Hatha yoga but positively correlated in Africa dance and biology. CONCLUSIONS: Both African dance and Hatha yoga reduced perceived stress and negative affect. Cortisol increased in African dance and decreased in Hatha yoga. Therefore, even when these interventions produce similar positive psychological effects, the effects may be very different on physiological stress processes. One factor that may have particular salience is that amount of physiological arousal produced by the intervention

Using overnight metyrapone and combined dexamethasone/metyrapone tests, hypothalamic-pituitary-adrenocortical (HPA) axis feedback regulation was characterised in 10 patients with post-traumatic stress disorder (PTSD) and 10 matched healthy comparison subjects. Significant treatment effects of both metyrapone and the combination of dexamethasone and metyrapone were observed for adrenocorticotropic hormone (ACTH), 11-deoxycortisol (11-DOC) and cortisol, but no differences between patients and comparison subjects emerged. Dose-response studies using metyrapone and glucocorticoid agonists are needed to further investigate HPA axis regulation in PTSD

Alterations of the retinoblastoma (RB1) tumor suppressor gene are not only associated with retinoblastoma but also with several other malignancies including osteosarcoma. Besides direct sequence alterations, hypermethylation of a CpG island in the promoter region can cause inactivation of the RB1 gene as it has been shown in retinoblastomas. We examined the methylation status of the RB1 gene in 25 osteosarcoma specimens by using the methylation-sensitive restriction enzymes SacII and SmaI. The restriction fragments were hybridized with clone p123, which is a 1.8-kb genomic subclone that spans the RB1 CpG island including the promoter region and exon 1. Whereas we reconfirmed hypermethylation of the RB1 gene in a sporadic retinoblastoma, no hypermethylation could be detected in the 25 osteosarcoma specimens, suggesting that hypermethylation of the RB1 promoter is not of major importance during osteosarcoma genesis

BACKGROUND: In patients with coronary heart disease (CHD), depression leads to worse cardiovascular outcomes. Depression has been associated with increased cortisol in medically healthy patients, suggesting that cortisol may act as a mediator in the pathway between depression and cardiovascular events. However, it is not known whether depression is associated with elevated cortisol levels in patients with CHD. METHODS: We examined the association between depression (assessed by the Computerized Diagnostic Interview Schedule) and 24-hour urinary cortisol in 693 medical outpatients with known CHD. RESULTS: Of 693 participants, 138 (20%) had current depression. Depressed participants had greater mean cortisol levels than those without depression (42 +/- 25 vs. 36 +/- 20 microg/day, p <.01). With each increasing quartile of cortisol concentration the frequency of depression increased (p <.01). Participants in the highest quartile of cortisol had a twofold increased odds of having depression, compared with those in the lowest quartile (odds ratio [OR] 2.1, 95% confidence interval [CR] 1.2-3.6, p =.01). This association remained strong after adjusting for potential confounding variables (OR 2.4, 95% CI 1.3-4.4, p <.01). In this cross-sectional analysis, elevated cortisol was not associated with worse cardiac function. CONCLUSIONS: In patients with CHD,depression is associated with elevated cortisol levels

In aged humans, diminished mineralocorticoid receptor (MR)-mediated feedback in the brain could contribute to impaired feedback regulation of the hypothalamic-pituitary-adrenal (HPA) axis, but no study specifically compared young and old individuals with regard to MR function. We examined 10 healthy young (mean age +/- SD [standard deviation] 26.1 +/- 2.9 years) and 10 elderly men (68.3 +/- 4.7 years) at the nadir of cortisol levels (2:00 pm-9:00 pm) when HPA activity is mainly controlled by the MR. After pretreatment with 3 g metyrapone to minimize the impact of basal endogenous cortisol secretion, participants received orally, in randomized order on two separate occasions, either 0.5 mg of the MR agonist fludrocortisone or placebo. Fludrocortisone significantly decreased maximum adrenocorticotropic hormone (ACTH) and cortisol concentrations in both groups. ACTH and cortisol values after fludrocortisone were significantly higher in older men compared with young men. Our results implicate that a decrease in MR-mediated negative feedback contributes to the diminished feedback activity in older humans