Sleep deprivation effects on the activity of the hypothalamic-pituitary-adrenal and growth axes: potential clinical implications

OBJECTIVES Although several studies have shown that sleep deprivation is as sociated with increased slow wave sleep during the recovery night, the effe cts of sleep deprivation on cortisol and growth hormone (GH) secretion the next day and recovery night have not been assessed systematically. We hypot hesized that increased slow wave sleep postsleep deprivation is associated with decreased cortisol levels and that the enhanced GH secretion is driven by the decreased activity of the HPA axis. DESIGN AND SUBJECTS After four consecutive nights in the Sleep Laboratory, 10 healthy young men were totally deprived of sleep during the fifth night, and then allowed to sleep again on nights six and seven. Twenty-four hour blood sampling was performed serially every 30 minutes on the fourth day, i mmediately following the previous night of sleep and on the sixth day, imme diately after sleep deprivation. MEASUREMENT Eight-hour sleep laboratory recording, including electroencepho logram, electro-oculogram and electromyogram. plasma cortisol and GH levels using specific immunoassay techniques. RESULTS Mean plasma and time-integrated (AUC) cortisol levels were lower du ring the postdeprivation nighttime period than on the fourth night (P<0.05) . Pulsatile analysis showed significant reduction of both the 24 h and dayt ime peak area (P<0.05) and of the pulse amplitude (P<0.01), but not of the pulse frequency. Also, the amount of time-integrated GH was significantly h igher for the first 4 h of the postdeprivation night compared to the predep rivation night (P<0.05). Cross-correlation analyses between the absolute va lues of the time-series of each hormone value and percentage of each sleep stage per half hour revealed that stow wave sleep was negatively correlated with cortisol and positively correlated with GH with slow wave sleep prece ding the secretion of these hormones. In contrast, indices of sleep disturb ance, i.e. wake and stage 1 sleep, were positively correlated with cortisol and negatively correlated with GH. CONCLUSION We conclude that steep deprivation results in a significant redu ction of cortisol secretion the next day and this reduction appears to be, to a large extent, driven by the increase of stow wave sleep during the rec overy night. We propose that reduction of CRH and cortisol secretion may be the mechanism through which sleep deprivation relieves depression temporar ily. Furthermore, deep sleep has an inhibitory effect on the HPA axis while it enhances the activity of the GH axis. In contrast, sleep disturbance ha s a stimulatory effect on the HPA axis and a suppressive effect on the GH a xis. These results are consistent with the observed hypocortisolism in idio pathic hypersomnia and HPA axis relative activation in chronic insomnia. Fi nally, our findings support previous hypotheses about the restitution and i mmunoenhancement role of slow wave (deep) sleep.