Neuroendocrine dysregulation in primary insomnia.

Recent research has pointed to a functional link between stress, disturbed sleep, psychiatric disorders, ageing, and neuroendocrine dysfunctions. In particular, increased activation of the hypothalamic-pituitary-adrenal (HPA) axis--expressed as elevated plasma cortisol levels--was shown in physiological ageing and patients with psychiatric disorders. We found increased evening and nocturnal plasma cortisol concentrations in patients with primary insomnia. Considering that both ageing and psychiatric disorders are commonly associated with sleep disturbances, our results implicate that elevated cortisol concentrations are a rather unspecific feature of disturbed sleep. Furthermore, our data revealed a strong positive correlation between evening cortisol secretion and the number of nocturnal awakenings in both insomniac patients and controls. Since nocturnal exposure to increased HPA activity promotes sleep fragmentation even in healthy controls, increased evening cortisol levels may be a crucial factor in inducing and maintaining sleep disturbances. We therefore propose a model of HPA dysregulation in insomnia. This model is based on the arousal theory of insomnia and the strong correlation between evening cortisol secretion and sleep fragmentation as a pathophysiological mechanism of a vicious cycle of insomnia. In patients with long-lasting insomniac complaints we found decreased nocturnal plasma melatonin levels thereby indicating a labilisation of circadian rhythm functions. Taken together, the neuroendocrine dysregulation seems to be more expressed in chronic insomnia than in acute insomnia and may be a contributing factor in maintaining disturbed sleep.