Jenny Choi, Steven R. Fauce, and Rita B. Effros
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Accelerated telomere shortening in lymphocytes has been associated with a variety of human pathologies, including HIV disease, Down syndrome, and cardiovascular disease. Recent findings indicate that reduced telomere length is also associated with chronic psychological stress and mood disorders. Telomerase, which prevents telomere shortening, can be upregulated in T lymphocytes in concert with activation, thereby retarding telomere shortening. Here, we demonstrate that exposure of human T lymphocytes to cortisol is associated with a significant reduction in telomerase activity both during primary stimulation of resting cells and secondary stimulation of previously activated cells. The effect is observed in both CD4 and CD8 T lymphocytes, and is associated with reduced transcription of hTERT, the telomerase catalytic component. These findings provide a potential mechanism for stress-associated telomere length attrition, and suggest that strategies to enhance T lymphocyte telomerase activity may provide beneficial effects on immune function in situations of chronic emotional stress.
Relation of cortisol levels and bone mineral density among premenopausal women with major depression
O. Altindag,1 A. Altindag,2 M. Asoglu,2 M. Gunes,2 N. Soran,1 Z. Deveci2
We aimed to investigate the relationship between cortisol levels and bone mineral density (BMD) among premenopausal women with major depression. We compared BMD, plasma cortisol, osteocalcin and C-telopeptide (CTx) levels of 36 premenopausal women with major depression with 41 healthy women who were matched for age and body mass index. Osteocalcin and CTx were used for the evaluation of bone turnover. The clinical diagnosis of major depression was made by using the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria. The 21-item Hamilton Rating Scale for Depression was used for the assessment of depressive symptoms. In comparison with the controls, the mean BMD of the depressed women was significantly lower at the lumbar spine and at all sites
of the proximal femur (p ¼ 0.02, 0.01). Plasma cortisol levels were significantly higher in depressive patients than in controls (p ¼ 0.001). Osteocalcin was lower and CTx was higher in the patient group than in controls (p ¼ 0.04, p ¼ 0.008). Lumbar and femur BMD scores were negatively correlated with cortisol levels in the patient group. Major depression had important effects on BMD and bone turnover markers. Depression should be considered among risk factors for osteoporosis in premenopausal women.
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Cortisol levels during human aging predict hippocampal atrophy and memory deficits
Sonia J. Lupien1,2, Mony de Leon3, Susan de Santi3, Antonio Convit3, Chaim Tarshish3, N.P.V.
Nair1, Mira Thakur1, Bruce S. McEwen4, Richard L. Hauger5 and Michael J. Meaney1
Correspondence should be addressed to S.J.L. (email@example.com)
Elevated glucocorticoid levels produce hippocampal dysfunction and correlate with individual
deficits in spatial learning in aged rats. Previously we related persistent cortisol increases to memory
impairments in elderly humans studied over five years. Here we demonstrate that aged humans with
significant prolonged cortisol elevations showed reduced hippocampal volume and deficits in
hippocampus-dependent memory tasks compared to normal-cortisol controls. Moreover, the degree
of hippocampal atrophy correlated strongly with both the degree of cortisol elevation over time and
current basal cortisol levels. Therefore, basal cortisol elevation may cause hippocampal damage and
impair hippocampus-dependent learning and memory in humans.
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Dysregulation of the hypothalamic-pituitary-adrenal axis has been suggested as an independent risk factor for ischemic heart disease. The aim of our study was to evaluate whether two markers of the hypothalamic-pituitary-adrenal axis activity, the level of salivary cortisol and the diurnal salivary cortisol pattern, are associated with atherosclerosis of the carotid arteries in an elderly population.
Methods and Results:
A total of 1866 participants of the Rotterdam Study, a population-based cohort study in the elderly, provided four salivary cortisol samples throughout 1 d, and underwent ultrasonography to examine the presence of plaques in the common, internal, and bifurcation sites of both carotid arteries. Two summary measures of the separate cortisol values were computed: area under the curve (AUC), which is a measure of total cortisol exposure while awake; and the slope, which is a measure of diurnal cortisol decline.
Total cortisol exposure while awake (AUC) was associated with higher plaque scores (β = 0.08 per sd of AUC, 95% confidence interval 0.00–0.16; P = 0.04) in a fully adjusted linear regression model. Persons with an AUC in the highest tertile had a higher number of plaques of carotid arteries compared with those in the lowest tertile (3.08 vs. 2.80, 95% confidence interval of difference 0.09–0.48; P = 0.005). There was no relation between diurnal cortisol decline and plaque score.
Our results support the hypothesis that increased total cortisol exposure is independently associated with atherosclerosis of the carotid arteries.
Am J Psychiatry. 2006 Dec;163(12):2164-9.
Plasma cortisol and progression of dementia in subjects with Alzheimer-type dementia.
Csernansky JG, Dong H, Fagan AM, Wang L, Xiong C, Holtzman DM, Morris JC.
Alzheimer’s Disease Research Center and the Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110, USA. firstname.lastname@example.org
Studies of subjects with dementia of the Alzheimer type have reported correlations between increases in activity of the hypothalamic-pituitary-adrenal (HPA) axis and hippocampal degeneration. In this study, the authors sought to determine whether increases in plasma cortisol, a marker of HPA activity, were associated with clinical and cognitive measures of the rate of disease progression in subjects with Alzheimer-type dementia.
Thirty-three subjects with very mild and mild Alzheimer-type dementia and 21 subjects without dementia were assessed annually for up to 4 years with the Clinical Dementia Rating scale and a battery of neuropsychological tests. Plasma was obtained at 8 a.m. on a single day and assayed for cortisol. Rates of change over time in the clinical and cognitive measures were derived from growth curve models.
In the subjects with dementia, but not in those without dementia, higher plasma cortisol levels were associated with more rapidly increasing symptoms of dementia and more rapidly decreasing performance on neuropsychological tests associated with temporal lobe function. No associations were observed between plasma cortisol levels and clinical and cognitive assessments obtained at the single assessment closest in time to the plasma collection.
Higher HPA activity, as reflected by increased plasma cortisol levels, is associated with more rapid disease progression in subjects with Alzheimer-type dementia
Psychosom Med. 2000 Sep-Oct;62(5):623-32.
Stress and body shape: stress-induced cortisol secretion is consistently greater among women with central fat.
Epel ES, McEwen B, Seeman T, Matthews K, Castellazzo G, Brownell KD, Bell J, Ickovics JR.
Health Psychology Program, University of California, San Francisco 94143-0848, USA. email@example.com
Excessive central fat puts one at greater risk of disease. In animal studies, stress-induced cortisol secretion has been shown to increase central fat. The objective of this study was to assess whether women with central fat distribution (as indicated by a high waist-to-hip ratio [WHR]), across a range of body mass indexes, display consistently heightened cortisol reactivity to repeated laboratory stressors.
Fifty-nine healthy premenopausal women, 30 with a high WHR and 29 with a low WHR, were exposed to consecutive laboratory sessions over 4 days (three stress sessions and one rest session). During these sessions, cortisol and psychological responses were assessed.
Women with a high WHR evaluated the laboratory challenges as more threatening, performed more poorly on them, and reported more chronic stress. These women secreted significantly more cortisol during the first stress session than women with a low WHR. Furthermore, lean women with a high WHR lacked habituation to stress in that they continued to secrete significantly more cortisol in response to now familiar challenges (days 2 and 3) than lean women with a low WHR.
Central fat distribution is related to greater psychological vulnerability to stress and cortisol reactivity. This may be especially true among lean women, who did not habituate to repeated stress. The current cross-sectional findings support the hypothesis that stress-induced cortisol secretion may contribute to central fat and demonstrate a link between psychological stress and risk for disease
From the Douglas Hospital Research Centre and McGill University, Verdun, Quebec, Canada
Received 2 December 1987; received in revised form 10 March 1988
The authors thank D. P. Dastoor, M. A., and C. Gendron, Ph.D., for conducting the neuropsychological evaluation. The authors gratefully acknowledge the assistance of all the following nursing staff at the Clinical Investigation Unit, Douglas Hospital Research Centre: M. Jumoorty, S. Larue, M. Nguyen, M. Paquette, L. Lorinatis, L. Lange, S. Golim, B. Bouchard, and S. Doyon. The expert secretarial assistance of Mrs. D. Vetro and Mrs. J. Currie is acknowledged.
The relationship of age to the circadian rhythms of melatonin and cortisol was investigated in 44 men and 27 women (age range 19–89 years). Subjects were physically and psychiatrically normal. Four hourly serial blood samples were drawn from 8:00 am until 8:00 am the next day, with additional samples at 10:00 pm and 2:00 am. The indoor illumination was restricted to 300 lux during day and 50 lux during the night. Plasma melatonin and cortisol were estimated by radioimmunoassay. Results show that the means of melatonin and cortisol values decreased significantly with age when the subjects were divided into three age groups, i.e., 19–25 years, 42–65 years, and 66–89 years. They also showed a significant negative correlation with age. The acrophases of the two hormonal rhythms, however, showed different relationships to age. The acrophase of melatonin rhythm showed a positive correlation with age (r = 0.38, p < 0.001), and cortisol showed a negative correlation with age (r = −0.56, p > 0.001). It is suggested that this may indicate a weakened responsiveness of the circadian system in the elderly to the day-night cycle and an altered relationship between the pacemakers driving melatonin and cortisol circadian rhythms. This may thus represent a biomarker for the intrinsic process of the aging of the brain.