Stress and sleep-wake regulation Animal and human studies showed that both acute and chronic stress have pronounced effects on sleep that are mediated through the activation of the HPA axis and the sympathetic system.13 For instance, in rats, effects of

acute #NF-��B inhibitor randurls[1|1|,|CHEM1|]# stress on sleep are primarily manifested by changes in REM sleep. These alterations seem to involve CRH-mediated mechanisms: CRH acts as a neurotransmitter in the LC to increase activity of the NE neurons, which leads to an increase in REM sleep.14 Rats exposed to various models of chronic stress have shown sleep disruption, increase in REM sleep, and decrease in SWS.15,16 There are also Inhibitors,research,lifescience,medical indications Inhibitors,research,lifescience,medical that CRH could contribute to the regulation of spontaneous waking even in the absence of stressors.17 In humans, there is a close temporal relationship between HPA activity and sleep structure. The HPA axis is subject, to a pronounced inhibition during the early phase of nocturnal sleep, during which SWS predominates. In contrast, during late sleep, when REM sleep predominates, HPA activity increases to reach a diurnal maximum shortly after morning awakening. During SWS, sympathetic activity is reduced and there Inhibitors,research,lifescience,medical is positive correlation among the amount of REM sleep and activities of the HPA axis and the sympathetic system.18-19 More generally, a close

coupling has been shown between adrenocorticotropic, autonomic, and EEG indices of arousal during the sleep-wake cycle.20-22 Exogenous administration of CRH, adrenocorticotropic hormone (ACTH), or Cortisol produces either prolonged sleep onset, reduced SWS, and increased sleep fragmentation.13 Accordingly, patients Inhibitors,research,lifescience,medical with complaints of insomnia show electrophysiological and psychomotor evidence of increased daytime arousal,23-25 as well as indications of increased HPA activity26 and increased sympathetic tone.27 Sleep complaints and anxiety disorder Anxiety disorders are considered Inhibitors,research,lifescience,medical as the most, frequently occurring category of mental disorder in the general population. Estimates

of the lifetime prevalence of anxiety disorders have ranged between 10% and 25 %.28 Epidemiological studies have also demonstrated the high prevalence of sleep complaints. As much as one third of the adult population those reports difficulty sleeping29-31 and sleep disturbance is considered as the second most common symptom of mental distress.32 Some epidemiological studies investigated the relationship between the occurrence of sleep disturbances and anxiety disorder in the general population.1,2,33 In a longitudinal study of young adults, Breslau et al2 found that lifetime prevalence was 16.6% for insomnia alone, 8.2% for hypersomnia alone, and 8% for insomnia plus hypersomnia. Odds ratios for various anxiety disorder diagnoses associated with lifetime sleep disturbance varied from 1.2 to 13.1.