Chronic insomnia is associated with nyctohemeral activation of the hypothalamic-pituitary-adrenal axis: Clinical implications

Although insomnia is, by far, the most commonly encountered sleep disorder in medical practice, our knowledge in regard to its neurobiology and medica l significance is limited. Activation of the hypothalamic-pituitary-adrenal axis leads to arousal and sleeplessness in animals and humans; however, th ere is a paucity of data regarding the activity of the hypothalamic-pituita ry-adrenal axis in insomniacs. We hypothesized that chronic insomnia is ass ociated with increased plasma levels of ACTH and cortisol. Eleven young ins omniacs (6 men and 5 women) and 13 healthy controls (9 men and 4 women) wit hout sleep disturbances, matched for age and body mass index, were monitore d in the sleep laboratory for 4 consecutive nights, whereas serial 24-h pla sma measures of ACTH and cortisol were obtained during the fourth day. Inso mniacs, compared with controls, slept poorly (significantly higher sleep la tency and wake during baseline nights). The 24-hACTH and cortisol secretion s 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 um, P = 0.07). Within the 24-h period, the greatest elevations were obse rved in the evening and first half of the night. Also, insomniacs with a hi gh 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 peak s per 24 h in insomniacs than in controls (P < 0.05), whereas cosinor analy sis showed no differences in the temporal pattern of ACTH or cortisol secre tion between insomniacs and controls. We conclude that insomnia is associat ed with an overall increase of ACTH and cortisol secretion, which, however, retains a normal circadian pattern. These findings are consistent with a d isorder of central nervous system hyperarousal rather than one of sleep los s' which is usually associated with no change or decrease in cortisol secre tion or a circadian disturbance. Chronic activation of the hypothalamic-pit uitary-adrenal axis in insomnia suggests that insomniacs are at risk not on ly for mental disorders, i.e. chronic anxiety and depression, but also for significant medical morbidity associated with such activation. The therapeu tic goal in insomnia should be to decrease the overall level of physiologic and emotional arousal, and not just to improve the nighttime sleep.