The role of peptides in disturbed sleep in depression

Abstract

Most patients with depression report disturbed sleep.1 Correspondingly sleep-EEG changes are frequent symptoms of depression. Furthermore a set of neuroendocrine aberrances, particularly overactivity of the hypothalamopituitary-adrenocortical (HPA) system and changes of the hypothalamo-pituitary-somatotrophic (HPS) system is characteristically in affective disorders. Since sleep is a time of considerable activity in endocrine systems it is an attractive approach to study sleep EEG and, by blood sampling during sleep via long catheter, nocturnal hormone secretion simultaneously. In young normal human subjects characteristical patterns of sleep-endocrine activity are found. During the first half of the night the major amounts of slow-wave sleep (SWS), slow-wave activity (SWA) and the growth hormone (GH) surge preponderate, whereas cortisol secretion reaches its nadir. During the second half of the night cortisol levels rise, the major portion of rapid-eyemovement sleep (REMS) occurs, and the amounts of SWS and GH are low2,3 (see Figure 1). Already this pattern points to a reciprocal interaction between the HPS and the HPA systems with GH and cortisol, respectively, as their peripheral endpoints. Furthermore it is likely that common factors are links between the electrophysiological and the endocrine activity during sleep. This hypothesis is supported, since during depression (and similarly during normal aging) SWS and GH decrease, whereas HPA activity is enhanced. Clinical and preclinical studies showed that neuropeptides are these factors. Ehlers and Kupfer4 submitted first that a reciprocal interaction of the peptides corticotropin-releasing hormone (CRH) and GHreleasing hormone (GHRH) plays a key role in the pathophysiology of changes of sleep-endocrine activity in depression. Since then this view was corroborated and amplified. This chapter intends to present the state of the art in this field