Human sleep is characterized by an electrophysiological and a neuroendocrine component. The cyclic occurrence of episodes of non-rapid eye movement (nonREM) and rapid eye movement (REM) sleep is recorded by the sleep electroencephalogram (EEG). Nocturnal blood sampling by a long catheter helps to show distinct patterns of the secretion of various hormones. In young normal subjects, during the first half of the night the major amount of slow wave sleep (SWS) and, as assessed by EEG spectral analysis, of slow wave activity (SWA) occurs. Around sleep onset, the growth hormone (GH) surge is found, whereas corticotropin (ACTH) and cortisol levels reach their nadir. During the second half of the night, REM sleep and sleep stage 2 preponderate, ACTH and cortisol reach their acrophase, while GH release is low. During an episode of depression and during normal ageing, similar changes of sleep-endocrine activity occur, including decreases of SWS, REM latency and GH, sleep fragmentation and elevated cortisol levels.
Since 1981, the interest of our laboratory has been to investigate the interaction of the sleep EEG and sleep-associated hormone secretion. Our aim is to elucidate physiological sleep regulation, the profiles and mechanisms of the action of central nervous system-active drugs and hormones, and the pathophysiology of psychiatric disorders, particularly of depression and of neurobiological dysfunction during ageing. To this end, combined studies of the sleep EEG and nocturnal hormone secretion are performed in young and old normal controls, in acutely and remitted depressed patients, and in patients with schizophrenia, with obsessive compulsive disorder and with endocrine and neurological disorders. We study these female and male subjects under baseline conditions, after sleep deprivation and after administration of psychotropic drugs, neuropeptides (e.g. growth hormone-releasing hormone [GHRH], ghrelin, somatostatin, corticotropin-releasing hormone [CRH]) and steroids (e.g. cortisol, progesterone).
Furthermore, we are searching sleep EEG variables which can help to predict treatment response and long-term outcome of depression. In addition, we examine the effects of specific antidepressants on the sleep EEG. In healthy subjects, learning shows a marked improvement after nocturnal sleep. We investigate the effects of depressive episodes, antidepressants, hormones and selective awakenings in specific sleep stages on sleep-associated memory consolidation.
Finally, we are interested in the pathophysiology of sleep disturbances, particularly narcolepsy. This rare sleep disorder is characterized by excessive daytime sleepiness, cataplectic attacks (sudden and transient episodes of loss of muscle tone, often triggered by emotions) and impaired sleep-wake regulation related to a loss of orexin-producing hypothalamic cells. Orexin interacts with various neuropeptides which participate in the regulation of sleep, appetite, body weight and metabolism. Previous studies in our Institute showed increases of body mass index and appetite at the onset of narcolepsy. At the same time, the hormone leptin is blunted. Preliminary results of ongoing studies suggest that an impaired glucose metabolism in patients with narcolepsy is independent from body weight. In addition, an increasing population of narcoleptic patients is screened for signs of the metabolic syndrome and cardiovascular risks including their eating behaviour.
Furthermore, we conduct clinical trials to determine the efficiency and the neurobiological effects of antidepressants and hypnotics.