Diurnal activity and pulsatility of the hypothalamus-pituitary-adrenal system in male depressed patients and healthy controls

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 08000800 h with 30-min sampling intervals was performed; from 18002400 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.