Diurnal Activity and Pulsatility of the Hypothalamus-Pituitary-Adrenal System in Male Depressed Patients and Healthy Controls

Abstract

There is only sparse and ambiguous information about circadian and pulsatile secretion features of the hypothalamus-pituitary-adrenocortical system in depression. We studied 15 severely depressed (Hamilton Depression Scale 30.4 +/- 6.7) male patients (age 22-72 yr; mean, 47.7 +/- 14.8) and 22 age-matched male controls (age 23-85 yr; mean, 53.1 +/- 18.2). Twenty-four-hour blood sampling from 0800-0800 h with 30-min sampling intervals was performed; from 1800-2400 h, blood was drawn every 10 min. Multivariate analysis of covariance, with the covariate being age, revealed mean 24-h cortisol (315.9 +/- 58.5 vs. 188.2 +/- 27.3 nmol/L) and mean ACTH (7.82 +/- 1.94 vs. 5.79 +/- 1.28 pmol/L) to be significantly increased in depressed patients. The frequency of cortisol (2.6 +/- 0.7 vs. 1.3 +/- 1.0 pulses/6 h) and ACTH (2.6 +/- 1.6 vs. 1.6 +/- 1.4 pulses/6 h) pulses during the evening were higher in patients compared to controls. The flattened circadian cortisol variation and reduced time of quiescence of cortisol secretory activity (140 +/- 116 vs. 305 +/- 184 min) in patients suggest disturbances of circadian functions. We conclude that increased hypothalamus-pituitary-adrenocortical activity in depression is related to a greater frequency of episodic hormone release, and we hypothesize that the observed circadian changes might be partly due to altered mineralocorticoid and glucocorticoid receptor capacity and function.

Chronic stress and obesity: A new view of “comfort food”

“…In young women, both groups have only slightly elevated circadian ACTH and cortisol concentrations (60). However, in an older male depressed population and in elderly males and females, the HPA axis is disturbed, particularly in those with melancholic depression (61)(62)(63). Moreover, cerebrospinal fluid samples from patients with atypical and melancholic depression indicate that atypical depressives have normal CRF and catecholamine concentrations, whereas melancholic depressives have abnormal elevations in both (58,64,65).…”

Approach to patients with pseudo-Cushing’s states

“…Overall, about 20-30% of patients with MDD reveal hypercortisolemia (15,16). Depressed male patients appear to have a more reliable cortisol hypersecretion, raising the issue of sex differences in HPA axis hyperactivity in depressed patients (16,17) (Table 1).…”

Transition to Kindergarten: Negative Associations between the Emotional Availability in Mother–Child Relationships and Elevated Cortisol Levels in Children with an Immigrant Background

“…A meta-analysis has shown that chronic stress is associated with flatter cortisol slopes across the day, a decreased overall diurnal cortisol level as well as higher cortisol levels in the afternoon and lower levels in the morning (Miller et al, 2007). For example, chronically depressed patients show a decreased or rather flatter decline in cortisol levels across the day (Deuschle et al, 1997; den Hartog et al, 2003). In addition, several studies have demonstrated that lacking positive and supportive relationships with the primary caregivers during childhood can evoke changes of the typical diurnal cortisol pattern, too (Gunnar, 2000; Tarullo and Gunnar, 2006; Roisman et al, 2009).…”

“…In addition, several studies have demonstrated that lacking positive and supportive relationships with the primary caregivers during childhood can evoke changes of the typical diurnal cortisol pattern, too (Gunnar, 2000; Tarullo and Gunnar, 2006; Roisman et al, 2009). Deviations from the typical diurnal cortisol pattern have been found, for example, in traumatized, neglected and abused children (Deuschle et al, 1997; Gunnar and Vazquez, 2001) 3 . To conclude, previous research indicates how important it is to reduce stress in early childhood and to support children’s ability to regulate stress effectively.…”