Dysregulated diurnal cortisol pattern is associated with glucocorticoid resistance in women with major depressive disorder

Feb 16, 2013Biological psychology

Irregular daily cortisol levels linked to reduced hormone sensitivity in women with major depression

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Abstract

Depressed women exhibited flatter diurnal cortisol rhythms and more impaired suppression of cortisol following dexamethasone administration compared to non-depressed women.

Dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis may contribute to the pathophysiology of depression.
Flatter diurnal cortisol slopes were observed in 26 pre-menopausal depressed women compared to 23 never depressed women.
Impaired cortisol suppression following dexamethasone administration was noted in depressed women.
Flatter diurnal cortisol slopes were associated with reduced cortisol response to dexamethasone treatment.
Increased self-reported depression severity correlated with flatter diurnal cortisol slopes in depressed women.

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Dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis is believed to play a role in the pathophysiology of depression. To investigate mechanisms that may underlie this effect, we examined several indices of HPA axis function - specifically, diurnal cortisol slope, cortisol awakening response, and suppression of cortisol release following dexamethasone administration - in 26 pre-menopausal depressed women and 23 never depressed women who were matched for age and body mass index. Salivary cortisol samples were collected at waking, 30 min after waking, and at bedtime over three consecutive days. On the third day, immediately after the bedtime sample, participants ingested a 0.5mg dexamethasone tablet; they then collected cortisol samples at waking and 30 min after waking the following morning. As predicted, depressed women exhibited flatter diurnal cortisol rhythms and more impaired suppression of cortisol following dexamethasone administration than non-depressed women over the three sampling days. In addition, flatter diurnal cortisol slopes were associated with reduced cortisol response to dexamethasone treatment, both for all women and for depressed women when considered separately. Finally, greater self-reported depression severity was associated with flatter diurnal cortisol slopes and with less dexamethasone-related cortisol suppression for depressed women. Depression in women thus appears to be characterized by altered HPA axis functioning, as indexed by flatter diurnal cortisol slopes and an associated impaired sensitivity of cortisol to dexamethasone. Given that altered HPA axis functioning has been implicated in several somatic conditions, the present findings may be relevant for understanding the pathophysiology of both depression and depression-related physical disease.

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Dysregulated diurnal cortisol pattern is associated with glucocorticoid resistance in women with major depressive disorder

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