Sleep and circadian rhythm disruption are frequently observed in patients with psychiatric disorders and neurodegenerative disease. The abnormal sleep that is experienced by these patients is largely assumed to be the product of medication or some other influence that is not well defined. However, normal brain function and the generation of sleep are linked by common neurotransmitter systems and regulatory pathways. Disruption of sleep alters sleep-wake timing, destabilizes physiology and promotes a range of pathologies (from cognitive to metabolic defects) that are rarely considered to be associated with abnormal sleep. We propose that brain disorders and abnormal sleep have a common mechanistic origin and that many co-morbid pathologies that are found in brain disease arise from a destabilization of sleep mechanisms. The stabilization of sleep may be a means by which to reduce the symptoms of--and permit early intervention of--psychiatric and neurodegenerative disease.

Sleep and circadian rhythm disruption in psychiatric and neurodegenerative disease

Cyclic alternating pattern (CAP): The marker of sleep instability

http://if-pan.krakow.pl/pjp/pdf/2009/3_383.pdf

Physiology and pharmacology of melatonin in relation to biological rhythms.

Benzodiazepine sedative-hypnotic drugs are widely used for the treatment of insomnia. Nevertheless, their adverse effects, such as next-day hangover, dependence and impairment of memory, make them unsuitable for long-term treatment. Melatonin has been used for improving sleep in patients with insomnia mainly because it does not cause hangover or show any addictive potential. However, there is a lack of consistency on its therapeutic value (partly because of its short half-life and the small quantities of melatonin employed). Thus, attention has been focused either on the development of more potent melatonin analogs with prolonged effects or on the design of slow release melatonin preparations. The MT(1) and MT(2) melatonergic receptor ramelteon was effective in increasing total sleep time and sleep efficiency, as well as in reducing sleep latency, in insomnia patients. The melatonergic antidepressant agomelatine, displaying potent MT(1) and MT(2) melatonergic agonism and relatively weak serotonin 5HT(2C) receptor antagonism, was found effective in the treatment of depressed patients. However, long-term safety studies are lacking for both melatonin agonists, particularly considering the pharmacological activity of their metabolites. In view of the higher binding affinities, longest half-life and relative higher potencies of the different melatonin agonists, studies using 2 or 3mg/day of melatonin are probably unsuitable to give appropriate comparison of the effects of the natural compound. Hence, clinical trials employing melatonin doses in the range of 50-100mg/day are warranted before the relative merits of the melatonin analogs versus melatonin can be settled.

/pdf/melatonin-and-its-analogs-in-insomnia-and-depression-hvoca2oi77.pdf

Melatonin and its analogs in insomnia and depression.

Sleep changes in the disorder of insomnia: a meta-analysis of polysomnographic studies.

OBJECTIVE To clarify the relationship between sleep instability and subjective complaints in patients with upper airway resistance syndrome (UARS). METHODS Thirty subjects (15 women) with UARS and 30 age- and sex-matched controls in a prospective, single-blind, case-control study. Blinded cyclic alternating pattern (CAP) electroencephalogram analysis and scales of fatigue and sleepiness were completed. ANALYSIS Mann-Whitney U tests for independent, nonparametric variables between groups and chi2 tests for nonparametric variables with defined standard values. RESULTS Patients with UARS had significantly more complaints of fatigue and sleepiness, compared with controls, demonstrated on their Fatigue Severity Scale (P < 0.001) and Epworth Sleepiness Scale (P < 0.001). By design, the mean apnea-hypopnea index was normal in both groups, whereas the respiratory disturbance index was greater in patients with UARS than in those without (14.5 +/- 3.0 vs 9 +/- 5.2, respectively [P < 0.001]). CAP analysis demonstrated abnormal non-rapid eye movement sleep with abnormally increased CAP rate, electroencephalogram arousals, A2 index, and A3 index. Decreased A1 index in controls was consistent with their more normal progression of sleep. CAP rate correlated with both the Epworth Sleepiness Scale (r = 0.38, P < 0.01) and the Fatigue Severity Scale (r = 0.51, P < 0.0001), and there was a positive trend between the Fatigue Severity Scale and phase A2 index (r = 0.29, P < 0.05). CONCLUSION Compared with age- and sex-matched controls, patients with UARS have higher electroencephalogram arousal indexes and important non-rapid eye movement sleep disturbances that correlate with subjective symptoms of sleepiness and fatigue. These disturbances are identifiable with sensitive measures such as CAP analysis but not with traditional diagnostic scoring systems.

The cyclic alternating pattern demonstrates increased sleep instability and correlates with fatigue and sleepiness in adults with upper airway resistance syndrome.

Non-REM sleep instability in patients with major depressive disorder: Subjective improvement and improvement of non-REM sleep instability with treatment (Agomelatine)

M. Cecilia Lopes

Papers

The cyclic alternating pattern demonstrates increased sleep instability and correlates with fatigue and sleepiness in adults with upper airway resistance syndrome.

Non-REM sleep instability in patients with major depressive disorder: Subjective improvement and improvement of non-REM sleep instability with treatment (Agomelatine)