Journal of Circadian Rhythms - Latest Articles

Insomnia in chronic renal patients on dialysis in Saudi Arabia

Hamdan Al-Jahdali — 2010-06-14T00:00:00Z

Background: Studies have shown that insomnia is a common sleep disorder among patients with end-stage renal disease (ESRD). This study aimed to assess the prevalence of insomnia in Saudi patients with ESRD who are on maintenance dialysis. Methods: This was an observational cross-sectional study carried out over a period of five months in two hemodialysis centers in Saudi Arabia. To assess the prevalence of insomnia, we used the ICSD-2 definition. We also examined the association between insomnia and other sleep disorders, the underlying causes of renal failure, dialysis duration, dialysis shift, and other demographic data. Results: Out of 227 enrolled patients, insomnia was reported by 60.8%. The mean patient age was 55.7 ± 17.2 years; 53.7% were male and 46.3% were female. Insomnia was significantly associated with female gender, afternoon hemodialysis, Restless Legs Syndrome, high risk for obstructive Sleep Apnea Syndrome and excessive daytime sleepiness (P-values: 0.05, 0.01, < 0.0001, < 0.0001, and < 0.0001, respectively). No significant association was found between insomnia and other variables, including BMI, smoking habits, underlying etiology of renal failure, dialysis duration, association with hemoglobin, ferritin, and phosphorus or dialysis adequacy as measured by the Kt/V index. Conclusion: Insomnia is common in dialysis patients and was significantly associated with other sleep disorders. Greater attention needs to be given to the care of dialysis patients with regard to the diagnosis and management of insomnia and associated sleep disorders.

Aging related changes of circadian rhythmicity of cytotoxic lymphocyte subpopulations

Gianluigi Mazzoccoli — 2010-05-25T00:00:00Z

Background: Immunosenescence is a process that affects all cell compartments of the immune system and the contribution of the immune system to healthy aging and longevity is still an open question. Lymphocyte subpopulations present different patterns of circadian variation and in the elderly alteration of circadian rhythmicity has been evidenced. The aim of our study was to analyze the dynamics of variation of specific cytotoxic lymphocyte subsets in old aged subjects. Methods: Lymphocyte subpopulation analyses were performed and cortisol serum levels were measured on blood samples collected every four hours for 24 hours from fifteen healthy male young-middle aged subjects (age range 36-55 years) and fifteen healthy male old aged subjects (age range 67-79 years). Results: In healthy young-middle aged subjects CD20 were higher and at 06:00 h CD8+ dim correlated positively with CD16+ and positively with γδTCR+ cells, CD16 correlated positively with γδTCR+ cells At 18:00 h CD8+ dim correlated positively with CD16+ and positively with γδTCR+ cells, CD16+ correlated positively with γδTCR+ cells and a clear circadian rhythm was validated for the time-qualified changes of CD3+, CD4+, CD20+, CD25+ and HLA-DR+ cells with acrophase during the night and for the time-qualified changes of CD8+, CD8+ bright, CD8+ dim, CD16+ and γδTCR+ cells with acrophase during the day. In old aged subjects CD25, DR+ T cells and cortisol serum levels were higher, but there was no statistically significant correlation among lymphocyte subpopulations and a clear circadian rhythm was evidenced for time-qualified changes of CD3+ and CD25+ cells with acrophase during the night and for the time-qualified changes of CD8+ cells and cortisol with acrophase during the day. Conclusion: Our study has evidenced aging-related changes of correlation and circadian rhythmicity of variation of cytotoxic lymphocyte subpopulations that might play a role in the alteration of immune system function in the elderly.

Weak evidence of bright light effects on human LH and FSH

Daniel Kripke — 2010-05-11T00:00:00Z

Background: Most mammals are seasonal breeders whose gonads grow to anticipate reproduction in the spring and summer. As day length increases, secretion increases for two gonadotropins, luteinizing hormone (LH) and follicle stimulating hormone (FSH). This response is largely controlled by light. Light effects on gonadotropins are mediated through effects on the suprachiasmatic nucleus and responses of the circadian system. There is some evidence that seasonal breeding in humans is regulated by similar mechanisms, and that light stimulates LH secretion, but primate responses seem complex. Methods: To gain further information on effects of bright light on LH and FSH secretion in humans, we analyzed urine samples collected in three experiments conducted for other goals. First, volunteers ages 18-30 years and 60-75 commenced an ultra-short 90-min sleep-wake cycle, during which they were exposed to 3000 lux light for 3 hours at balanced times of day, repeated for 3 days. Urine samples were assayed to explore any LH phase response curve. Second, depressed participants 60-79 years of age were treated with bright light or dim placebo light for 28 days, with measurements of urinary LH and FSH before and after treatment. Third, women of ages 20-45 years with premenstrual dysphoric disorder (PMDD) were treated to one 3-hour exposure of morning light, measuring LH and FSH in urine before and after the treatments. Results: Two of the three studies showed significant increases in LH after light treatment, and FSH also tended to increase, but there were no significant contrasts with parallel placebo treatments and no significant time-of-day treatment effects. Conclusions: These results gave some support for the hypothesis that bright light may augment LH secretion. Longer-duration studies may be needed to clarify the effects of light on human LH and FSH.

"Time sweet time": circadian characterization of galectin-1 null mice

Leandro Casiraghi — 2010-04-19T00:00:00Z

Background: Recent evidence suggests a two-way interaction between the immune and circadian systems. Circadian control of immune factors, as well as the effect of immunological variables on circadian rhythms, might be key elements in both physiological and pathological responses to the environment. Among these relevant factors, galectin-1 is a member of a family of evolutionarily-conserved glycan-binding proteins with both extracellular and intracellular effects, playing important roles in immune cell processes and inflammatory responses. Many of these actions have been studied through the use of mice with a null mutation in the galectin-1 (Lgals1) gene. To further analyze the role of endogenous galectin-1 in vivo, we aimed to characterize the circadian behavior of galectin-1 null (Lgals1 -/-) mice. Methods: We analyzed wheel-running activity in light-dark conditions, constant darkness, phase responses to light pulses (LP) at circadian time 15, and reentrainment to 6 hour shifts in light-dark schedule in wild-type (WT) and Lgals1 -/- mice. Results: We found significant differences in free-running period, which was longer in mutant than in WT mice (24.02 vs 23.57 h, p < 0.005), phase delays in response to LP (2.92 vs 1.90 circadian h, p < 0.05), and also in alpha (14.88 vs. 12.35 circadian h, p < 0.05). Conclusions: Given the effect of a null mutation on circadian period and entrainment, we indicate that galectin-1 could be involved in the regulation of murine circadian rhythmicity. This is the first study implicating galectin-1 in the mammalian circadian system.

Circadian rhythm and its role in malignancy

Sobia Rana — 2010-03-31T00:00:00Z

Circadian rhythms are daily oscillations of multiple biological processes directed by endogenous clocks. The circadian timing system comprises peripheral oscillators located in most tissues of the body and a central pacemaker located in the suprachiasmatic nucleus (SCN) of the hypothalamus. Circadian genes and the proteins produced by these genes constitute the molecular components of the circadian oscillator which form positive/negative feedback loops and generate circadian rhythms. The circadian regulation extends beyond clock genes to involve various clock-controlled genes (CCGs) including various cell cycle genes. Aberrant expression of circadian clock genes could have important consequences on the transactivation of downstream targets that control the cell cycle and on the ability of cells to undergo apoptosis. This may lead to genomic instability and accelerated cellular proliferation potentially promoting carcinogenesis. Different lines of evidence in mice and humans suggest that cancer may be a circadian-related disorder. The genetic or functional disruption of the molecular circadian clock has been found in various cancers including breast, ovarian, endometrial, prostate and hematological cancers. The acquisition of current data in circadian clock mechanism may help chronotherapy, which takes into consideration the biological time to improve treatments by devising new therapeutic approaches for treating circadian-related disorders, especially cancer.

Circadian light

Mark Rea — 2010-02-13T00:00:00Z

The present paper reflects a work in progress toward a definition of circadian light, one that should be informed by the thoughtful, century-old evolution of our present definition of light as a stimulus for the human visual system. This work in progress is based upon the functional relationship between optical radiation and its effects on nocturnal melatonin suppression, in large part because the basic data are available in the literature. Discussed here are the fundamental differences between responses by the visual and circadian systems to optical radiation. Brief reviews of photometry, colorimetry, and brightness perception are presented as a foundation for the discussion of circadian light. Finally, circadian light (CLA) and circadian stimulus (CS) calculation procedures based on a published mathematical model of human circadian phototransduction are presented with an example.

CLOCK is suggested to associate with comorbid alcohol use and depressive disorders

Louise Sjoholm — 2010-01-21T00:00:00Z

Background: Depression and alcohol abuse or dependence (AUD) co-occur in the general population more frequently than expected by chance. Alcohol use influences the circadian rhythms generated by the central pacemaker in the suprachiasmatic nucleus, and circadian rhythm alterations in turn are common in depressive disorders as well as among persons addicted to alcohol. Methods: 32 SNPs in 19 circadian clockwork related genes were analyzed using DNA from 76 individuals with comorbid depression and AUD, 446 individuals with AUD and 517 healthy controls with no psychiatric diagnosis. The individuals participated in a nationwide health examination study, representative of the general population aged 30 and over in Finland. Results: The CLOCK haplotype TTGC formed by SNPs rs3805151, rs2412648, rs11240 and rs2412646, was associated with increased risk for comorbidity (OR = 1.65, 95% CI = 1.14-2.28, P = 0.0077). The SNPs of importance for this suggestive association were rs2412646 and rs11240 indicating location of the functional variation in the block downstream rs2412648. There was no indication for association between CLOCK and AUD. Conclusion: Our findings suggest an association between the CLOCK gene and the comorbid condition of alcohol use and depressive disorders. Together with previous reports it indicates that the CLOCK variations we found here may be a vulnerability factor to depression given the exposure to alcohol in individuals having AUD.

Impact of oral melatonin on the electroretinogram cone response

Anne-Marie Gagne — 2009-11-19T00:00:00Z

Background: In the eye, melatonin plays a role in promoting light sensitivity at night and modulating many aspects of circadian retinal physiology. It is also an inhibitor of retinal dopamine, which is a promoter of day vision through the cone system. Consequently, it is possible that oral melatonin (an inhibitor of retinal dopamine) taken to alleviate circadian disorders may affect cone functioning. Our aim was to assess the impact of melatonin on the cone response of the human retina using electroretinography (ERG). Methods: Twelve healthy participants aged between 18 to 52 years old were submitted to a placebo-controlled, double-blind, crossover, and counterbalanced-order design. The subjects were tested on 2 sessions beginning first with a baseline ERG, followed by the administration of the placebo or melatonin condition and then, 30 min later, a second ERG to test the effect. Results: Following oral melatonin administration, a significant decrease of about 8% of the cone maximal response was observed (mean 6.9 μV ± SEM 2.0; P = 0.0065) along with a prolonged b-wave implicit time of 0.4 ms ± 0.1, 50 minutes after ingestion. Conclusion: Oral melatonin appears to reach the eye through the circulation. When it is administered at a time of day when it is not usually present, melatonin appears to reduce input to retinal cones. We believe that the impact of melatonin on retinal function should be taken into consideration when used without supervision in chronic self-medication for sleep or circadian disorder treatment.

Sex and hand differences in circadian wrist activity are independent from sex and hand differences in 2D:4D

Camille Reuter — 2009-10-29T00:00:00Z

Background: We investigated the relationship between patterns of sex and hand differences in circadian wrist activity and digit ratio, a marker for prenatal androgen exposure. If the contribution of prenatal androgen exposure to sex differences in digit ratio underlies sex differences in circadian wrist activity, we predict that patterns of wrist activity will be correlated with digit ratio. Methods: Bilateral wrist activity of male and female college students was measured for three consecutive days. Digit ratio was obtained from photocopy measurements of the second and fourth fingers of each subject. Results: Males had lower digit ratios with more pronounced differences on the right hand. Female acrophase occurred earlier than male acrophase. There was more activity in the right hand and right hand activity peaked before the left. Digit ratio was not correlated with any measure of wrist activity. An analysis of activity by age revealed that younger female students exhibited more male-like activity patterns. Conclusion: Sex and hand differences for digit ratio and acrophase replicated previous findings. The lack of correlation between digit ratio and patterns of wrist activity suggests that sexually dimorphic circadian activity develops independently from the mechanisms of hormone exposure that cause sex differences in digit ratio.

Restless Legs Syndrome in shift workers: A cross sectional study on male assembly workers

Akbar Sharifian — 2009-09-14T00:00:00Z

Background: Restless Legs Syndrome (RLS) is a common neurological movement disorder characterized by symptoms that follow a circadian pattern. Night and rotating shift work schedules exert adverse effects on functions of the human body by disturbing circadian rhythms, and they are known to cause sleep disturbances and insomnia. In this paper, we investigate the possible association between shift work and RLS. Methods: This cross sectional study was conducted in an automobile manufacturing factory in Tehran, Iran. A total of 780 male assembly workers were recruited in three groups, each with 260 workers: workers on a permanent morning shift (A) and two different rotating shift schedules (B and C) with morning, afternoon and night shifts. We used the international RLS study group criteria for diagnosis of RLS, and the severity scale for severity assessment in subjects with RLS. Self administered questionnaires were used to gather information on age, smoking, work history, medical condition, and existence and severity of RLS symptoms. Results: The prevalence of RLS was significantly higher in rotational shift workers (15%) than workers with permanent morning work schedule (8.5%). In workers suffering from RLS, we found greater mean values of age and work experience, higher percentages of drug consumption, smoking, and co-morbid illnesses compared with subjects who did not have RLS, although these differences were statistically significant only for age, work experience and drug consumption. Conclusion: Rotational shift work acts as a risk or exacerbating factor for Restless Legs Syndrome.