Molecular clock genes in man and lower animals: possible implications for circadian abnormalities in depression. (1/275)

This paper reviews the recent discovery of clock genes that provide the mechanism for the regulation of circadian and seasonal rhythms in lower organisms and in humans and relates these clock genes to the circadian abnormalities in depression. (1) A subgroup of depressed patients have documented circadian abnormalities in mood, sleep, temperature and neuroendocrine secretion; (2) It is also suggested that seasonal affective disorder (SAD) patients may show an abnormality in their ability to shift their daily circadian rhythms in response to seasonal light changes; (3) The dramatic improvements in some depressions in response to three treatment modalities which manipulate circadian rhythms suggest that circadian abnormalities reported in patients may constitute a core component of the pathophysiology in depression; (4) Mutations in clock genes have been discovered that accelerate or delay circadian cycles; (5) It is hypothesized that 24-hour rhythm abnormalities in major depression and SAD may be due to altered clock genes.  (+info)

Long-term effects of CPAP on daytime functioning in patients with sleep apnoea syndrome. (2/275)

Daytime sleepiness, impaired cognitive performance and dysphoric mood are often present in patients with obstructive sleep apnoea syndrome (SAS). This prospective controlled study evaluates the effects of treatment with continuous positive airway pressure (CPAP) during 1 yr on daytime functioning in a large group of patients with SAS. The authors studied 80 patients (mean+/-sem 49+/-1 yrs) with SAS with a mean apnoea-hypopnoea index of 60+/-2 h-1, and 80 healthy control subjects matched for sex and age (46+/-1 yrs.). Measurements were obtained at the beginning of the study and 12+/-1 months later, and included: daytime sleepiness (Epworth scale), depression and anxiety (Beck tests), vigilance (Steer-Clear) and reaction time (Psychometer Vigilance Test 192). Drug, coffee and alcohol intake, as well as the sleep schedule, were also recorded. Results showed that, before treatment, patients were more somnolent (p<0.001), anxious (p<0.01) and depressed (p<0.001) than control subjects. Also, they had a longer reaction time (p<0.05) and poorer vigilance (p<0.01). The use of CPAP improved significantly the levels of somnolence (p<0.0001) and vigilance (p<0.01), but failed to modify anxiety and depression. Reaction time changes were minor. Variables with a potential confounding effect did not change during the study. These results provide firm evidence to substantiate the use of continuous positive airway pressure in patients with sleep apnoea syndrome.  (+info)

Towards the 24-hour society--new approaches for aging shift workers? (3/275)

The new "24-hour society" increases night work and the diversity of flexible work-hour patterns. At the same time, the number of older shift workers is growing in most developed countries due to the general aging of the working population. Together with new experimental and epidemiologic data on the alarming relationship of shift work to fatigue, performance, accidents, and chronic health effects like coronary heart disease, there is reason to believe that shift work may become a major occupational health and safety problem in the near future. The prevention of shiftwork-related health and safety problems will be a major challenge for the employer, employees, and occupational health professionals during the next few decades. The present paper shortly summarizes the current knowledge on the relationship between shift work, aging, and health and outlines practical countermeasures and research needs to improve the health and well-being of aging shift workers.  (+info)

Hypocretin-1 modulates rapid eye movement sleep through activation of locus coeruleus neurons. (4/275)

The hypocretins (hcrts), also known as orexins, are two recently identified excitatory neuropeptides that in rat are produced by approximately 1200 neurons whose cell bodies are located in the lateral hypothalamus. The hypocretins/orexins have been implicated in the regulation of rapid eye movement (REM) sleep and the pathophysiology of narcolepsy. In the present study, we investigated whether the locus coeruleus (LC), a structure receiving dense hcrtergic innervation, which is quiescent during REM sleep, might be a target for hcrt to regulate REM sleep. Local administration of hcrt1 but not hcrt2 in the LC suppressed REM sleep in a dose-dependent manner and increased wakefulness at the expense of deep, slow-wave sleep. These effects were blocked with an antibody that neutralizes hcrt binding to hcrt receptor 1. In situ hybridization and immunocytochemistry showed the presence of hcrt receptor 1 but not the presence of hcrt receptor 2 in the LC. Iontophoretic application of hcrt1 enhanced the firing rate of LC neurons in vivo, and local injection of hcrt1 into the LC induced the expression of c-fos in the LC area. We propose that hcrt receptor 1 in the LC is a key target for REM sleep regulation and might be involved in the pathophysiological mechanisms of narcolepsy.  (+info)

Comparing performance on a simulated 12 hour shift rotation in young and older subjects. (5/275)

OBJECTIVES: To simulate a 12 hour shift rotation and measure the difference in performance if any, between older and younger subjects. Significant reductions in neurobehavioural performance during shift work and particularly night work have long been recognised. There are conflicting reports of the effects of 12 hour shifts on performance, alertness, and safety. Furthermore, research suggests that older shift workers have more sleep disruption and maladaption to shift work. When this is combined with longer hours at work there may be considerable reductions in performance for older compared with younger workers. METHODS: Thirty two subjects were allocated to groups according to age. Group one had 16 subjects with a mean (SD) age of 21.2 (2.7) years, and group two had 16 subjects with a mean (SD) age of 43.9 (6.8) years. Subjects came to the laboratory for six consecutive days and completed a simulated 12 hour shift rotation consisting of two 12 hour day shifts (0700-1900), followed by two 12 hour night shifts (1900-0700). During the work period subjects completed a computer administered neurobehavioural performance task every hour. RESULTS: Performance for the older subjects was consistently lower than for the younger subjects. There was a significant difference in performance across the shift between older and younger subjects. There was a significant change in performance across the shifts in the older subjects, such that performance significantly increased across the day shifts and decreased across the night shifts. By contrast, the younger subjects were able to maintain performance across both day shifts and the second night shift. CONCLUSIONS: There are significant differences in performance of older and younger subjects during a simulated 12 hour shift rotation. Future studies both in the field and the laboratory would be useful in determining whether this is typical and if there are any important consequences for the older worker on 12 hour shifts.  (+info)

Actigraphic estimates of circadian rhythms and sleep/wake in older schizophrenia patients. (6/275)

Twenty-four hour circadian activity rhythms and light-exposure levels of 28 older schizophrenia patients (mean age=58years) were examined using an Actillume recorder. Sleep and wake were scored using the algorithm of the ACTION3 software which revealed that the patients slept for 67% of the night and napped for 9% of the day. Patients with more disturbed sleep and less robust circadian rhythms performed more poorly on neuropsychological tests. Patients with higher cognitive functioning and fewer extrapyramidal symptoms were more alert during the day. Few patients were exposed to high levels of illumination during the day, and older age was associated with lower levels of light exposure. Duration of antipsychotic use and higher antipsychotic doses were associated with decreased daytime alertness and less robust circadian activity rhythms. Patients taking antipsychotics were more sleepy both during the day and night than patients not taking antipsychotics. The circadian rhythm disturbances found in these patients did not seem to be due solely to low levels of illumination exposure. Life-style factors, behavioral factors, psychiatric symptoms and medications were likely contributors to the disturbed rhythms. The effects of the sleep disturbances did not seem to be benign. There were strong relationships between sleep and circadian rhythms and functioning.  (+info)

An hPer2 phosphorylation site mutation in familial advanced sleep phase syndrome. (7/275)

Familial advanced sleep phase syndrome (FASPS) is an autosomal dominant circadian rhythm variant; affected individuals are "morning larks" with a 4-hour advance of the sleep, temperature, and melatonin rhythms. Here we report localization of the FASPS gene near the telomere of chromosome 2q. A strong candidate gene (hPer2), a human homolog of the period gene in Drosophila, maps to the same locus. Affected individuals have a serine to glycine mutation within the casein kinase Iepsilon (CKIepsilon) binding region of hPER2, which causes hypophosphorylation by CKIepsilon in vitro. Thus, a variant in human sleep behavior can be attributed to a missense mutation in a clock component, hPER2, which alters the circadian period.  (+info)

Association of structural polymorphisms in the human period3 gene with delayed sleep phase syndrome. (8/275)

Recent progress in biological clock research has facilitated genetic analysis of circadian rhythm sleep disorders, such as delayed sleep phase syndrome (DSPS) and non-24-h sleep-wake syndrome (N-24). We analyzed the human period3 (hPer3) gene, one of the human homologs of the Drosophila clock-gene period (Per), as a possible candidate for rhythm disorder susceptibility. All of the coding exons in the hPer3 gene were screened for polymorphisms by a PCR-based strategy using genomic DNA samples from sleep disorder patients and control subjects. We identified six sequence variations with amino acid changes, of which five were common and predicted four haplotypes of the hPer3 gene. One of the haplotypes was significantly associated with DSPS (Bonferroni's corrected P = 0.037; odds ratio = 7.79; 95% CI 1.59-38.3) in our study population. Our results suggest that structural polymorphisms in the hPer3 gene may be implicated in the pathogenesis of DSPS.  (+info)