Cortisol escape from suppression by dexamethasone during depression is strongly predicted by basal cortisol hypersecretion and increasing age combined

Maes, Michaël; Minner, B.; Suy, E.; D'Hondt, Peter; Jacobs, M.-P.; Raus, Jef

doi:10.1016/0306-4530(91)90016-m

Cited by 16 publications

(4 citation statements)

References 61 publications

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“…The present results are consis tent with several correlational studies that have demon strated a positive relationship between age and plasma cortisol concentrations following the administration of dexamethasone to normal humans [18,19]. However, it has been more difficult to demonstrate an effect of aging on the HPA axis response to dexamethasone in studies directly comparing groups of healthy old and young sub jects.…”

Section: Discussionsupporting

confidence: 57%

Decreased Hypothalamic-Pituitary Adrenal Axis Sensitivity to Cortisol Feedback Inhibition in Human Aging

Wilkinson

Peskind

Raskind³

1997

Neuroendocrinology

164

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Aging-related reduction in the sensitivity of the hypothalamic-pituitary-adrenal (HPA) axis to glucocorticoid feedback inhibition has been demonstrated in rodents, but aging effects on glucocorticoid feedback inhibition in humans are unclear. This study assessed the influence of aging on the sensitivity of the human HPA axis to feedback inhibition induced by cortisol. Endogenous cortisol feedback inhibition was removed by treatment with metyrapone, which reduces cortisol synthesis by inhibiting 11β-hydroxylase. Feedback inhibition was then reintroduced by infusing exogenous cortisol. Sixteen young (26 ± 1 years old) and 16 older (70 ± 2 years old) subjects underwent three study conditions in random order. In the two cortisol infusion conditions, oral metyrapone treatment was followed by intravenous infusion of 0.03 mg/kg/h (83 nmol/kg/h) or 0.06 mg/kg/h (166 nmol/kg/h) cortisol for 150 min. Feedback sensitivity was estimated by the latency to and extent of decline of plasma ACTH concentration during and following the cortisol infusion. In a placebo condition, placebo tablets were substituted for metyrapone and normal saline infusion was substituted for cortisol. Blood samples were drawn twice prior to and at 15-min intervals for 4 h following the onset of the infusions, and plasma was assayed for 11-deoxycortisol, cortisol and ACTH. Plasma cortisol suppression and ACTH and 11-deoxycortisol elevations did not differ between age groups after metyrapone. Older subjects exhibited delayed and blunted ACTH responses to infused cortisol. Within older subjects, the ACTH response to the higher dose cortisol infusion was blunted in older women compared to older men. These data provide direct evidence for reduced responsiveness to glucocorticoid feedback inhibition in human aging.

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Section: Discussionsupporting

confidence: 57%

Decreased Hypothalamic-Pituitary Adrenal Axis Sensitivity to Cortisol Feedback Inhibition in Human Aging

Wilkinson

Peskind

Raskind³

1997

Neuroendocrinology

164

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“…One possible explanation is that these differences occur because younger and older depressed patients differ in endocrine regulation and response. For insta:nce, with advancing age, depression is more likely to be accompanied by basal cortisol hypersecretion and cortisol nonsuppression after dexamethasone administration (15)(16)(17). It is also possible, however, that the health practices of younger and older patients differ or that poor health practices among older patients are more detrimental than they are among the young.…”

Section: Introductionmentioning

confidence: 99%

Pathways Linking Major Depression and Immunity in Ambulatory Female Patients

Miller

Cohen

Herbert

1999

Psychosomatic Medicine

124

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Objectives: The goals of this study were to investigate whether depression is associated with cellular immunity in ambulatory patients and to identify neuroendocrine and behavioral pathways that might account for this relationship. Methods: We studied 32 women who met Diagnostic and Statistical Manual of Mental Disorder, fourth edition, criteria for major depressive disorder and 32 healthy female control subjects. The groups were matched for age and ethnicity. None were taking medication, and all were free of disease involving the immune system. Results: Depressed subjects had reduced proliferative responses to the mitogens concanavalin A and phytohemagglutinin compared with control subjects. Natural killer cell activity was reduced among older depressed subjects but enhanced among younger depressed subjects. Although depression was associated with elevated circulating levels of norepinephrine and estradiol, these hormones could not account for the immunologic differences between depressed and control subjects. Depression was also associated with greater tobacco and caffeine consumption, less physical activity, and poorer sleep quality. Mediational analyses were consistent with physical activity acting as a pathway through which depression was associated with reduced lymphocyte proliferation. Conclusions: Ambulatory patients with mild to moderately severe depression exhibit reduced mitogen-stimulated lymphocyte proliferative responses and altered natural killer cell cytotoxicity. The relationship between depression and proliferative responses may be mediated by physical activity.

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“…Apart from an activated immune system, there is also clear evidence for a disturbed activity of the hypothalamus–pituitary–adrenal (HPA) axis, both in BD (25–27) and in MD (28–30). First, cortisol levels are increased in both disorders (28, 30, 31), which interestingly is not accompanied by obvious signs of Cushing's syndrome (32). Second, the dexamethasone (DEX) suppression test (29) and the DEX/corticotropin‐releasing hormone (CRH) test (27, 33) are disturbed, indicating a relative steroid resistance.…”

mentioning

confidence: 99%