Chronic Insomnia Is Associated with Nyctohemeral Activation of the Hypothalamic-Pituitary-Adrenal Axis: Clinical Implications

Abstract

Although insomnia is, by far, the most commonly encountered sleep disorder in medical practice, our knowledge in regard to its neurobiology and medical significance is limited. Activation of the hypothalamic-pituitary-adrenal axis leads to arousal and sleeplessness in animals and humans; however, there is a paucity of data regarding the activity of the hypothalamic-pituitary-adrenal axis in insomniacs. We hypothesized that chronic insomnia is associated with increased plasma levels of ACTH and cortisol. Eleven young insomniacs (6 men and 5 women) and 13 healthy controls (9 men and 4 women) without sleep disturbances, matched for age and body mass index, were monitored in the sleep laboratory for 4 consecutive nights, whereas serial 24-h plasma measures of ACTH and cortisol were obtained during the fourth day. Insomniacs, compared with controls, slept poorly (significantly higher sleep latency and wake during baseline nights). The 24-h ACTH and cortisol secretions were significantly higher in insomniacs, compared with normal controls (4.2 +/- 0.3 vs. 3.3 +/- 0.3 pM, P = 0.04; and 218.0 +/- 11.0 vs. 190.4 +/- 8.3 nM, P = 0.07). Within the 24-h period, the greatest elevations were observed in the evening and first half of the night. Also, insomniacs with a high degree of objective sleep disturbance (% sleep time < 70), compared with those with a low degree of sleep disturbance, secreted a higher amount of cortisol. Pulsatile analysis revealed a significantly higher number of peaks per 24 h in insomniacs than in controls (P < 0.05), whereas cosinor analysis showed no differences in the temporal pattern of ACTH or cortisol secretion between insomniacs and controls. We conclude that insomnia is associated with an overall increase of ACTH and cortisol secretion, which, however, retains a normal circadian pattern. These findings are consistent with a disorder of central nervous system hyperarousal rather than one of sleep loss, which is usually associated with no change or decrease in cortisol secretion or a circadian disturbance. Chronic activation of the hypothalamic-pituitary-adrenal axis in insomnia suggests that insomniacs are at risk not only for mental disorders, i.e. chronic anxiety and depression, but also for significant medical morbidity associated with such activation. The therapeutic goal in insomnia should be to decrease the overall level of physiologic and emotional arousal, and not just to improve the nighttime sleep.

Association between Job Stress and Insomnia in Korean Workers

“…First, some studies 35,36) found that job stress is related with the increase of cortisol, and it was reported that cortisol and the activity of hypothalamic-pituitary-adrenal (HPA) axis are associated with sleep disorder 37,38) . Accordingly, the activation of HPA axis by job stress is likely to cause sleep disorder.…”

The Pathophysiology of Insomnia

“…As early as 1967, Monroe 104 showed that poor sleepers had increased body temperature, vasoconstrictions, body movements, and skin resistance as compared with good sleepers. Insomnia has also been associated, in some studies, with increased 24-h metabolic rate (as measured by oxygen consumption), 27 , 105 24-h adrenocorticotropic hormone and cortisol levels, 51 and heart rate. 106 Some investigators have demonstrated greater inhibition of facial muscle activity and increased cardiac vagal tone in response to sleep-related emotional stimuli among individuals with insomnia as compared with good sleepers.…”

Stress-related sleep disturbance and polysomnographic response to caffeine

“…However, there is an increasing body of literature regarding the psychological and physiological differences between insomniacs and good sleepers. Several studies have demonstrated a greater prevalence of intrusive thoughts, worry, and rumination [8], poor sleep hygiene [9,10], dysregulation of the hypothalamic pituitary axis [11], elevations in sympathetic activity [12], and metabolic rate [13], increased daytime alertness [14], and elevated high-frequency electroencephalographic (EEG) activity [15][16][17] in patients with insomnia compared to good sleepers.…”