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.

Flattening the Glucocorticoid Rhythm causes Changes in Hippocampal Expression of Messenger RNAs Coding Structural and Functional Proteins: Implications for Aging and Depression

“…The corticosterone profile generated is very similar to that seen in aged rats (Hauger et al, 1994) and similar to the profile of cortisol levels in aged human subjects (Deuschle et al, 1997a;Ferrari et al, 2001;Van Cauter et al, 1996;Wong et al, 2000). The elevated nadir and flattened rhythm is also consistent with the pattern observed in depressed patients, although in this group the peak of the diurnal rhythm is preserved, or even marginally elevated, resulting in an increase in 24 h cortisol exposure (Deuschle et al, 1997b;Wong et al, 2000). Aging and depressive illnesses are both accompanied by cognitive deficits, including impairments in aspects of memory function (Golomb et al, 1996;Mayeux et al, 2001;Austin et al, 2001;Quraishi and Frangou, 2002), which are believed to be hippocampally mediated (Silva et al, 1998).…”

“…Thus in the normal aging process, there is a significant flattening of the normal diurnal rhythm of cortisol secretion (Ferrari et al, 2001;Van Cauter et al, 1996;Deuschle et al, 1997a). In addition, several common psychiatric disorders including affective disorders, cortisol secretion is moderately increased and there is a marked flattening of the diurnal rhythm (Deuschle et al, 1997b;Ferrari et al, 2001).…”

Depressive Symptoms and 24-Hour Urinary Norepinephrine Excretion Levels in Patients With Coronary Disease: Findings From the Heart and Soul Study

“…However, a plausible mechanism linking depressive symptoms with increased sympathetic activity is the enhanced activity of hypothalamic and extrahypothalamic corticotropin-releasing factor (CRF) in depressed patients. It is well established that CRF is increased in medically healthy patients with depressive symptoms (10,32), leading to increased cortisol levels (33)(34)(35). Moreover, a large body of evidence suggests that both hypothalamic and extrahypothalamic CRF activate the locus ceruleus in the brain, leading to an increase in norepinephrine (36)(37)(38)(39).…”

Depression and 24-hour urinary cortisol in medical outpatients with coronary heart disease: The Heart and Soul Study

“…Depression is associated with elevated levels of cortisol in medically healthy patients (Anton 1987;Carroll et al 1976;Deuschle et al 1997;Halbreich et al 1985;Posener et al 2000;Young et al 1994); however, it is not known whether depression is associated with elevated cortisol in patients with CHD.…”