9. Dysregulated diurnal cortisol pattern and increased glucocorticoid resistance among pre-menopausal women with major depressive disorder

Abstract

Women are approximately twice as likely to experience depression compared to men and are at significantly greater risk for developing comorbid physical health conditions, including diabetes, chronic inflammatory diseases, and cardiovascular disease, suggesting a possible common mechanism for the psychological and physical health risks seen in depression. We examined one biological pathway that may underlie these effects by investigating the extent to which HPA axis activity was dysregulated in 26 women with current major depression and 23 age- and BMI-matched psychiatrically healthy women. Salivary cortisol samples were collected at wakening, 30 min later, and at bedtime over three consecutive days. Depressed women exhibited flatter diurnal cortisol slopes compared to non-depressed women ( F 2 = 5.52, p = .004). To investigate whether these differences could be attributed to differences in glucocorticoid feedback sensitivity, saliva samples were also collected on a fourth consecutive day after participants self-administered dexamethasone. Analyses revealed that depressed women exhibited a dampened response to dexamethasone compared to non-depressed women ( F 1 = 6.04, p = .015). These findings are consistent with previous studies showing that depression is associated with altered HPA axis regulation, but extend this work by showing that reduced hypothalamic and pituitary sensitivity to negative feedback from glucocorticoids is one mechanism that may explain this effect. Altered glucocorticoid sensitivity may play a role in promoting depression as well as the physical health complications that frequently co-occur with this serious psychiatric disorder.