Kegg Pathway: Circadian rhythm

Actas Esp Psiquiatr. 2009 Jul; 37(4): 222-232
Soria V, Urretavizcaya M

Some core symptoms of major depression show a Circadian rhythm in their clinical manifestations or are intimately linked to the Circadian system functioning, such as sleep-wake cycle. Moreover, abnormalities in Circadian rhythms of core body temperature and some endocrinemetabolic parameters have been detected in depressive patients compared to healthy controls. The Circadian rhythm disturbances described in depressive states as well as the efficacy and fast onset of action of chronobiological based treatments point out the Circadian system as antherapeutic target in the treatment of depression. The aim of this work is to review the biological and clinical data that link major depression to Circadian rhythm abnormalities, the mechanisms that may underlie the abnormalities of Circadian rhythm physiology seen in depressive states and the different therapeutic approaches to depression that involve the Circadian system in their mechanisms of action. Key words: Depression. Mood disorders. Circadian rhythms. Chronobiology. important Actas Esp Psiquiatr 2009;37(4):222-232.

J Biol rhythms. 2009 Dec; 24(6): 497-508
Morin LP, Studholme KM

Masking, measured as a decrease in nocturnal rodent wheel running, is a visual system response to rod/cone and retinal ganglion cell photoreception. Here, the authors show that a few milliseconds of light are sufficient to initiate masking, which continues for many minutes without additional photic stimulation. C57J/B6 mice were tested using flash stimuli previously shown to elicit large Circadian rhythm phase shifts. Ten flashes, 2 msec each and equally distributed over 5 min, activate locomotor suppression that endures for an additional 25 to 35 min in the dark and does not differ in magnitude or duration from that elicited by 5-min saturating light pulse. Locomotor activity by mice without access to running wheels is also suppressed by light flashes. The effects of various light flash patterns on mouse locomotor suppression are similar to those previously described for hamster phase shifts. Video analysis of active mice indicates that light flashes initiated at ZT13 rapidly induce an interval of behavioral quiescence that lasts about 10 min at which time the animals assume a typical sleep posture that is maintained for an additional 25 min. Thus, the period coincident with light-induced wheel running suppression appears to consist of two distinct behavioral states, one interval during which locomotor quiescence is initiated and maintained, followed by a second interval characterized by behavioral sleep. Given this sequence effected by light stimulation, we suggest that it be referred to as "photosomnolence," the term reflecting upon both the nature of the stimulus and the associated behavioral change.

J Biol rhythms. 2009 Dec; 24(6): 488-496
Lesauter J, Bhuiyan T, Shimazoe T, Silver R

Calbindin-D28K (CalB)-containing cells form a distinct cluster within the core of the hamster suprachiasmatic nucleus (SCN). These cells are directly retinorecipient but lack detectable rhythms in clock gene expression or electrical activity. In studies exploring SCN connectivity using double-label immunochemistry, we previously reported an absence of contacts among CalB fibers and vasopressin (VP) cells in animals sacrificed during the day. Here, we explored Circadian variations in CalB-immunoreactivity (-ir) and re-examined the connections between CalB and other SCN cell types at zeitgeber times (ZT) 4 and 14. The results reveal a Circadian rhythm of CalB-ir in fibers of SCN cells with high expression during the night and subjective night and low expression during the day and subjective day. This Circadian difference is not seen in the other brain regions studied. Significantly more appositions were detected between CalB fibers and VP cells during the night than during the day, while Circadian variation in numbers of contacts was not seen between CalB fibers and vasoactive intestinal polypeptide (VIP), cholecystokinin (CCK), or gastrin-releasing peptide (GRP) cells. There was no detectable variation in appositions from any peptidergic fiber type onto CalB cells. The present findings suggest that CalB cells relay photic information to VP oscillator cells of the SCN shell in a temporally gated manner.

Integr Cancer Ther. 2009 Nov 18;
Yang X, Wood P, Ansell C, Hrushesky WJ

The mammalian core clock genes, Periods (Per1 and Per2), have tumor suppressor properties. Decreased expression of Per1 and Per2 has been reported in several types of human cancers. On the other hand, overexpression of Per1 or Per2 inhibits cancer cell growth in culture. The authors have shown that downregulation of Per1 or Per2 enhances cancer growth in vitro. These genes also regulate the amount of cell proliferation-related molecules, many of which are therapeutic targets. In animals, tumors grow with clear Circadian organization, and Per1 and Per2 exert their tumor suppressor functions in a Circadian time-dependent manner. Downregulation of Per1 or Per2 increases tumor growth only at certain specific times of the day. Per1 and Per2 differentially regulate tumor growth rhythm in vivo. These data suggest that the therapeutic efficacy of antiproliferation agents depends on the time of day of drug delivery. The optimal times of day may be shifted in tumors that have mutant Period genes.

J Neurosci. 2009 Nov 18; 29(46): 14681-14686
Pendergast JS, Friday RC, Yamazaki S

The mammalian Circadian pacemaker in the suprachiasmatic nuclei (SCN) controls daily rhythms of behavior and physiology. Lesions of the SCN cause arrhythmicity of locomotor activity, and transplants of fetal SCN tissue restore rhythmic behavior that is consistent with the periodicity of the donor's genotype, suggesting that the SCN determines the period of the Circadian behavioral rhythm. While several studies have demonstrated that the Circadian characteristics of in vitro SCN rhythms represent Circadian behavior, others have shown that the periods of explanted SCN are not always congruent with locomotor activity. We find that the aberrant rhythms of ex vivo SCN lacking functional Period1 (Per1(-/-)) do not represent the behavioral rhythms of the mutant animals. Surprisingly, in C57BL/6J Per1(-/-) mice, the real-time Circadian gene promoter activity rhythm is weak or absent in adult SCN slices in vitro even though the free-running wheel-running activity rhythm is indistinguishable from wild-type (Per1(+/+)) mice. While some neurons in Per1(-/-) SCN explants exhibit robust Circadian rhythms, others have irregular and/or low-amplitude rhythms. Together, these data suggest that either a small population of rhythmic neurons in the Per1(-/-) SCN is sufficient to control wheel-running activity or that in vivo physiological factors can compensate for the aberrant endogenous rhythms of Per1(-/-) SCN.

Mol Brain. 2009 Nov 19; 2(1): 34
Hosoda H, Kato K, Asano H, Ito M, Kato H, Iwamoto T, Suzuki A, Masusige S, Kida S

ABSTRACT: BACKGROUND: Previous studies have demonstrated tissue-specific regulation of the rhythm of Circadian transcription, suggesting that transcription factor complex CLOCK/BMAL1, essential for maintaining Circadian rhythm, regulates transcription in a tissue-specific manner. To further elucidate the mechanism of the cell type-specific regulation of transcription by CLOCK/BMAL1 at the molecular level, we investigated roles of CBP/p300 and tissue-specific cofactors in CLOCK/BMAL1-mediated transcription. RESULTS: As shown previously, CBP/p300 stimulates CLOCK/BMAL1-mediated transcription in COS-1 cells. However, CBP/p300 repressed CLOCK/BMAL1-mediated transcription in NIH3T3 cells and knockdown of CBP or p300 expression by siRNA enhanced this transcription. Studies using GAL4-fusion proteins suggested that CBP represses CLOCK/BMAL1-mediated transcription by targeting CLOCK. We further investigated mechanisms of this cell type-specific modulation of CLOCK/BMAL1-mediated transcription by CBP by examining roles of co-repressor HDAC3 and co-activator pCAF, which are highly expressed in NIH3T3 and COS cells, respectively. CBP repressed CLOCK/BMAL1-mediated transcription in COS-1 cells when HDAC3 was overexpressed, but activated it in NIH3T3 cells when pCAF was overexpressed. CBP forms a complex with CLOCK by interacting with HDAC3 or pCAF; however, direct interaction of CBP with CLOCK was not observed. CONCLUSIONS: Our findings indicate possible mechanisms by which CBP/p300 tissue-specifically acts cooperatively with pCAF and HDAC3 either as a co-activator or co-repressor, respectively, for CLOCK/BMAL1.

Chronobiol Int. 2009 Oct; 26(7): 1430-42
Marpegan L, Leone MJ, Katz ME, Sobrero PM, Bekinstein TA, Golombek DA

Many immune parameters exhibit daily and Circadian oscillations, including the number of circulating cells and levels of cytokines in the blood. Mice also have a differential susceptibility to lipopolysaccharide (LPS or endotoxin)-induced endotoxic shock, depending on the administration time in the 24 h light-dark (LD) cycle. We replicated these results in LD, but we did not find temporal differences in LPS-induced mortality in constant darkness (DD). Animals challenged with LPS showed only transient effects on their wheel locomotor activity rhythm without modification of Circadian period and phase. Levels of several key factors involved in the pathology of sepsis and septic shock were tested in LD. We found that LPS-induced levels of interleukin (IL)-1beta, IL-6, JE (MCP-1), and MIP1alpha were significantly higher at zeitgeber time (ZT) 11 (time of increased mortality) than at ZT19 (ZT12 = time of lights-off in the animal quarters for the 12L:12D condition). Our results indicate that the differences found in mortality that are dependent on the time of LPS-challenge are not directly related to an endogenous Circadian clock, and that some relevant immune factors in the development of sepsis are highly induced at ZT11, the time of higher LPS-induced mortality, compared to ZT19.

Chronobiol Int. 2009 Oct; 26(7): 1389-408
López-Olmeda JF, Montoya A, Oliveira C, Sánchez-Vázquez FJ

Food is not continuously available in the wild, and so most animals show a wide variety of Circadian rhythms that can be entrained to feeding time. The aim of this research was to evaluate the effect of time-restricted feeding on the daily rhythms of gilthead sea bream, with food being provided during the day or night under a 12:12 h light-dark (LD) cycle or constant light (LL) conditions. Self-feeding and locomotor activity, as well as daily rhythms of cortisol, glucose, and melatonin, were evaluated. Fish synchronized their feeding behavior to the feeding phase, so that in LD they displayed 78% nocturnal feeding activity under night-feeding and 81% diurnal feeding activity under day-feeding, while under LL-feeding they displayed 72% of their daily activity during the 12 h feeding phase. In contrast, locomotor activity was mostly diurnal (66-71%), regardless of the feeding schedule, and it became arrhythmic under LL. Cortisol showed daily rhythms that peaked at different times, depending on the light and feeding schedule: one peak several hours before feeding under day-feeding and night-feeding, and two peaks under LL-feeding. Glucose displayed low-amplitude variations, with no daily rhythms being detected. Melatonin, however, showed a nocturnal rhythm, regardless of the feeding schedule, while the rhythm became attenuated under LL. Taken together, these results highlight the role of feeding on endocrine and metabolic rhythms, suggesting that feeding behavior should be considered when studying these variables.

Chronobiol Int. 2009 Oct; 26(7): 1369-88
Ellis DJ, Firth BT, Belan I

Australian sleepy lizards (Tiliqua rugosa) exhibit marked locomotor activity rhythms in the field and laboratory. Light-dark (LD) and temperature cycles (TCs) are considered important for the entrainment of Circadian locomotor activity rhythms and for mediating seasonal adjustments in aspects of these rhythms, such as phase, amplitude, and activity pattern. The relative importance of 24 h LD and TCs in entraining the Circadian locomotor activity rhythm in T. rugosa was examined in three experiments. In the first experiment, lizards were held under LD 12:12 and subjected to either a TC of 33:15 degrees C in phase with the LD cycle or a reversed TC positioned in antiphase to the LD cycle. Following LD 12:12, lizards were maintained under the same TCs but were subjected to DD. Activity was restricted to the thermophase in LD, irrespective of the lighting regime and during the period of DD that followed, suggesting entrainment by the TC. The amplitude of the TC was lowered by 8 degrees C to reduce the intensity and possible masking effect of the TC zeitgeber in subsequent experiments. In the second experiment, lizards were held under LD 12.5:11.5 and subjected to one of three treatments: constant 30 degrees C, normal TC (30:20 degrees C) in phase with the LD cycle, or reversed TC. Following LD, all lizards were subjected to DD and constant 30 degrees C. Post-entrainment free-run records revealed that LD cycles and TCs could both entrain the locomotor rhythms of T. rugosa. In LD, mean activity duration (alpha) of lizards in the normal TC group was considerably less than that in the constant 30 degrees C group. Mean alpha also increased between LD and DD in lizards in the normal TC group. Although there was large variation in the phasing of the rhythm in relation to the LD cycle in reversed TC lizards, TCs presented in phase with the LD cycle most accurately synchronized the rhythm to the photocycle. In the third experiment, lizards were held in DD at constant 30 degrees C before being subjected to a further period of DD and one of four treatments: normal TC (06:00 to 18:00 h thermophase), delayed TC (12:00 to 00:00 h thermophase), advanced TC (00:00 to 12:00 h thermophase), or control (no TC, constant 30 degrees C). While control lizards continued to free-run in DD at constant temperature, the locomotor activity rhythms of lizards subjected to TCs rapidly entrained to TCs, whether or not the TC was phase advanced or delayed by 6 h. There was no difference in the phase relationships of lizard activity rhythms to the onset of the thermophase among the normal, delayed, and advanced TC groups, suggesting equally strong entrainment to the TC in each group. The results of this experiment excluded the possibility that masking effects were responsible for the locomotor activity responses of lizards to TCs. The three experiments demonstrated that TCs are important for entraining Circadian locomotor activity rhythms of T. rugosa, even when photic cues are conflicting or absent, and that an interaction between LD cycles and TCs most accurately synchronizes this rhythm.

Chronobiol Int. 2009 Oct; 26(7): 1340-54
Otway DT, Frost G, Johnston JD

Adipose tissue is central to metabolic homeostasis, signaling in part through the secretion of molecules termed adipokines. Circadian rhythms play an important role in adipose physiology, with plasma adipokine concentration and approximately 20 % of the murine adipose transcriptome undergoing 24 h variation. However, due to the heterogeneity of adipose tissue and rhythmical input from both neuronal and humoral signals, the cellular basis of adipose rhythms is unclear. We tested the hypothesis that adipocyte cells contain a Circadian clock that drives rhythmic mRNA expression and adipokine secretion. From the murine pre-adipocyte 3T3-L1 cell line, we generated populations of both pre-adipocytes and differentiated adipocytes. Cells were then treated with a 2 h serum pulse and sampled every 4 h over a 48 h period. Expression of clock gene, 'metabolic' gene (PPARalpha, PPARgamma, SREBP1), and adipokine mRNA was analyzed by quantitative real-time PCR, and secretion of the adipokines leptin and adiponectin was measured in culture medium from differentiated adipocytes. In pre-adipocytes, we observed robust rhythms of clock genes Per2, Rev-erbalpha, and Dbp, but not of Per1, Cry1, Bmal1, or any of the 'metabolic' genes. Adipocytes produced similar temporal profiles of mRNA expression, albeit with a markedly reduced amplitude of Per2 and Dbp rhythms. Despite no Circadian rhythm of adipokine mRNA expression, leptin accumulation in the culture medium suggested Circadian control of leptin secretion from adipocytes. Adiponectin secretion showed temporal variation, but without any apparent Circadian rhythmicity. Our data, therefore, suggest that an endogenous adipocyte clock controls the rhythmic expression of only a subset of genes that are reported to exhibit 24 h rhythmicity in murine adipose tissue. Moreover, secretion of leptin may also be regulated by the adipocyte clock.

Chronobiol Int. 2009 Oct; 26(7): 1307-22
Wülbeck C, Grieshaber E, Helfrich-Förster C

The neuropeptide pigment-dispersing factor (PDF) plays an essential role in the Circadian clock of the fruit fly Drosophila melanogaster, but many details of PDF signaling in the clock network are still unknown. We tried to interfere with PDF signaling by blocking the GTPase Shibire in PDF neurons. Shibire is an ortholog of the mammalian Dynamins and is essential for endocytosis of clathrin-coated vesicles at the plasma membrane. Such endocytosis is used for neurotransmitter reuptake by presynaptic neurons, which is a prerequisite of synaptic vesicle recycling, and receptor-mediated endocytosis in the postsynaptic neuron, which leads to signal termination. By blocking Shibire function via overexpression of a dominant negative mutant form of Shibire in PDF neurons, we slowed down the behavioral rhythm by 3 h. This effect was absent in PDF receptor null mutants, indicating that we interfered with PDF receptor-mediated endocytosis. Because we obtained similar behavioral phenotypes by increasing the PDF level in regions close to PDF neurons, we conclude that blocking Shibire did prolong PDF signaling in the neurons that respond to PDF. Obviously, terminating the PDF signaling via receptor-mediated endocytosis is a crucial step in determining the period of behavioral rhythms.

Urology. 2009 Nov 13;
Hong YH, Dublin N, Razack AH, Mohd MA, Husain R

OBJECTIVES: To investigate the correlations and agreements between the solute/creatinine ratios from the 24-hour and early morning spot urine samples for metabolic evaluation in stone-formers given the various pitfalls with the 24-hour urinary metabolic evaluation in stone-formers. METHODS: 30 urinary stone-formers out of an initial 62 recruited provided a complete 24-hour urine and early morning spot urine samples for metabolic evaluation. Pearson correlation and Bland and Altman Test were used to assess the correlations and agreements. RESULTS: Significant correlations were established between the 24-hour urinary solute excretions and the corresponding early morning spot urine solute/creatinine ratios for calcium, magnesium, urate, potassium, oxalate, citrate, and the Differential Gibb's free energy value of calcium oxalate DG(CaOx) values. However, all these solute/creatinine measurements between the 24-hour and early morning spot urine samples were judged to be not within the acceptable limits based on the estimated "limit of agreement" by the Bland and Altman Test of Agreement. Diurnal Circadian rhythm and postprandial excretion surge are thought to be responsible for the disagreements. CONCLUSIONS: Thus, the early morning spot urine is not suitable to be used interchangeably to replace the 24-hour urine collection in the evaluation of urinary metabolic abnormalities in stone-formers. A good correlation does not translate to an agreement between the 2 measurements.

Neurosci Lett. 2009 Nov 12;
Hamada T, Shibata S

Gamma-aminobutyric acid (GABA), and its biosynthetic enzyme, glutamic decarboxylase, are widely distributed in the suprachasmatic nucleus (SCN). In the present study, we examined the role of the GABA(A) receptor on in vitro SCN responses to photic-like signals. We found that 100muM GABA(A) receptor antagonist bicuculline partially blocked field potentials evoked by optic nerve stimulation. NMDA- and SP-induced phase shifts of SCN neuronal activity rhythms, were blocked with 10muM bicuculline. Application of 100muM bicuculline alone induced phase advance of SCN neuronal activity rhythm. These results show that NMDA- and SP-induced phase shifts are blocked by bicuculline and suggest GABA has an important role as neurotransmitter in the neuronal network regulating phase shifts of the Circadian clock.

J Insect Physiol. 2009 Nov 10;
Stay B, Zera AJ

Previous studies have documented a Circadian cycle in juvenile hormone (JH) biosynthesis in the long-winged, flight-capable morph, but not in the short-winged flightless morph of the cricket Gryllus firmus. One rapid and reversible inhibitor of in vitro JH biosynthesis by the corpora allata (CA) in crickets is the neuropeptide Phe-Gly-Leu/Ile-amide type of allatostatins (ASTs). To investigate the possible role of allatostatin regulation of the morph-specific Circadian cycle of JH production, the quantity of this type of AST in the nerves within the CA was determined by the density of anti-AST-immunostaining in confocal images using the Image J program. The density of immunostaining was inversely related to the rate of JH biosynthesis: Immunostaining in the CA was high and did not differ between morphs early in the photophase when the in vitro rate of JH biosynthesis is low and equivalent in the morphs. However, during the end of the photophase, when the rate of JH biosynthesis rises dramatically in the flight-capable morph, but not in the flightless morph, immunostaining was significantly lower in the flight-capable compared to the flightless morph. These results indicate that morph-specific differences in delivery of AST to the CA and its probable release likely regulate the morph-specific Circadian pattern of JH biosynthesis. Also, the negative correlation between AST density and JH production provides evidence for predicting the periods of altered release of these rapid-acting paracine regulators of JH biosynthesis.

Rev Endocr Metab Disord. 2009 Nov 13;
Korkmaz A, Topal T, Tan DX, Reiter RJ

Although the human genome has remained unchanged over the last 10,000 years, our lifestyle has become progressively more divergent from those of our ancient ancestors. This maladaptive change became apparent with the Industrial Revolution and has been accelerating in recent decades. Socially, we are people of the 21st century, but genetically we remain similar to our early ancestors. In conjunction with this discordance between our ancient, genetically-determined biology and the nutritional, cultural and activity patterns in contemporary Western populations, many diseases have emerged. Only a century ago infectious disease was a major cause of mortality, whereas today non-infectious chronic diseases are the greatest cause of death in the world. Epidemics of metabolic diseases (e.g., cardiovascular diseases, type 2 diabetes, obesity, metabolic syndrome and certain cancers) have become major contributors to the burden of poor health and they are presently emerging or accelerating, in most developing countries. One major lifestyle consequence is light at night and subsequent disrupted Circadian rhythms commonly referred to as Circadian disruption or chronodisruption. Mounting evidence reveals that particularly melatonin rhythmicity has crucial roles in a variety of metabolic functions as an anti-oxidant, anti-inflammatory chronobiotic and possibly as an epigenetic regulator. This paper provides a brief outline about metabolic dysregulation in conjunction with a disrupted melatonin rhythm.

Am J Geriatr Psychiatry. 2009 Nov 10;
Wirz-Justice A, Schröder CM, Gasio PF, Cajochen C, Savaskan E

OBJECTIVES:: Alzheimer disease (AD) has been associated with diminished function of the biological clock in the suprachiasmatic nuclei (SCN) and pronounced Circadian sleep-wake cycle disturbances. Few studies have investigated other dementia etiologies. Because alcohol acts on the SCN and modifies Circadian rhythms in animal studies, Korsakoff psychosis (KP) may also be associated with Circadian rhythm abnormalities. This pilot study investigated the rest-activity cycle of KP to see whether there were sleep-wake cycle disturbances similar to those that the authors had observed in patients with AD. DESIGN AND SETTING:: Cross-sectional observational study in a single academic medical center. PARTICIPANTS, MEASUREMENTS:: The authors investigated the Circadian rest-activity cycle of six moderately demented patients with KP who wore an activity/lux monitor for 10-26 days and compared these patterns with those of six home-living healthy individuals of the same age group. In addition, rest-activity cycle data from previous studies of patients with AD were examined. INTERVENTIONS:: None. RESULTS:: The rest-activity cycle of KP was remarkably well entrained, without the marked Circadian and sleep disturbances found in patients with AD on the same ward. KP had a >2 hour earlier bedtime and rest onset than healthy subjects and a 30-minute earlier wake-up time, resulting in longer nocturnal rest duration. The major difference was a greatly diminished daytime activity level and extremely low light exposure. CONCLUSION:: A stably entrained, although low-amplitude and phase-advanced rest-activity cycle may reflect the different neuropathology of demented patients with KP compared with patients with AD.

Psychoneuroendocrinology. 2009 Nov 7;
Sjörs A, Larsson B, Karlson B, Osterberg K, Dahlman J, Gerdle B

This study investigated differences in HPA axis function, measured as salivary cortisol concentrations, between 18 women with chronic trapezius myalgia (MYA) and 30 healthy female controls (CON). In addition, the interactions between HPA axis reactions to psychosocial stress and aspects of pain, health and psychological symptoms were analyzed. Salivary cortisol was measured both in daily life, to assess the Circadian profile, and in the laboratory during light repetitive work and standardized psychosocial stress (Trier Social Stress Test, TSST). MYA and CON exhibited similar Circadian rhythms and comparable salivary cortisol response magnitudes after TSST. In subjects defined as responders to the TSST, the mean peak time point of the cortisol response after TSST differed significantly between MYA and CON. Furthermore, negative psychological states and higher pain intensity were related to a slower HPA axis response to TSST. Low Circadian variations in cortisol and smaller cortisol responses to TSST were found among subjects scoring high on anxiety sensitivity. Thus, a relatively favorable sample of female chronic trapezius myalgia patients exhibited normal Circadian rhythm and normal salivary cortisol response magnitudes after a psychosocial stress test. In the subgroup of responders, the MYA group showed indications of a slower salivary cortisol response to psychosocial stress. Further studies are needed to elucidate the possibility of altered HPA axis activity in terms of a slower salivary cortisol response.

J Occup Rehabil. 2009 Nov 8;
Bittencourt LR, Santos-Silva R, De Mello MT, Andersen ML, Tufik S

In recent decades, the hectic lifestyle of industrialized societies has wrought its effects on the quality of sleep, and these effects are evidenced by a profusion of sleep-related disorders. Regular exposure to artificial light, coupled with social and economic pressures have shortened the time spent asleep. Otherwise, Circadian rhythm Sleep Disorders are characterized by desynchronization between the intrinsic Circadian clock and the extrinsic cycles of light/dark and social activities. This desynchronization produces excessive sleepiness and insomnia. The International Classification of Sleep Disorders describes nine sleep disorders under the category of Circadian rhythm Sleep Disorders. Currently, this diagnosis is made based on the patient's history, a sleep log alone, or the sleep logs and actigraphy conducted for at least 7 days. This review contains an overview of current treatment options, including chronotherapy, timed bright light exposure, and administration of exogenous melatonin.

NeuroRehabilitation. 2009; 25(3): 189-99
Brawley EC

Good lighting is perhaps the most important and least understood element in designing healthcare environments. Both physically and mentally challenged individuals become more vulnerable and dependent on their environment to compensate for sensory impairments, including dimming eyesight, which interferes to some degree with daily activities as well as social and leisure activities - the things that provide emotional and social well-being. Too few building designs today result in lighting that meets the needs of these individuals, regardless of age. Typical lighting in most care environments is inadequate to meet lighting needs affecting both vision and the photobiological (non-visual) needs of synchronization of Circadian rhythm, which impacts sleep and depression. Well-designed lighting is one of the most important design elements that will support an individual's ability to perform normal daily activities and decrease the level of disability associated with these impairments. Daylight contains the spectrum to which the Circadian clock is most sensitive and provides higher light levels during the day. Easily accessible outdoor gardens encourage individuals outside, providing the necessary regular exposure to direct bright light that sunlight provides. The combination good interior lighting and regular daylight exposure contributes to regaining and maintaining an active and fulfilling lifestyle - greatly improving quality of life.

Eur J Intern Med. 2009 Dec; 20(8): 760-3
Castilla-Guerra L, Fernández-Moreno Mdel C, Espino-Montoro A, López-Chozas JM

BACKGROUND: We aim to evaluate prospectively the long-term changes of blood pressure (BP) in stroke survivors using ambulatory BP monitoring (ABPM) and compare them with the clinic conventional measurements. METHODS: We studied 101 patients who were admitted within 24h after stroke onset. To study the Circadian rhythm of BP a continuous BP monitor (Spacelab 90207) was used. After six and twelve months follow-up a new ABPM was undertaken. Data were analyzed using the SSPS 12.0. RESULTS: We studied 62 males and 39 females, mean age: 70.9+/-10.7 years. We included 88 ischemic strokes and 13 hemorrhagic strokes. In the acute phase mean 24 h BPs were 136+/-19/78.6+/-11.4 mm Hg. The normal diurnal variation in BP was abolished in 88 (87.1%) patients. After six months, 74 patients were assessed. Mean office readings were 137.5+/-23.8/76.4+/-11.4 mm Hg, and high systolic BPs and diastolic BPs were found in 37% and 11% of the subjects respectively. ABPM revealed a mean BP of 118.5+/-20.1/70.3+/-8.6 (p<0.0001). In 57 (76.9%), the normal BP pattern remained abolished (p<0.001). After one year, 63 patients were assessed. Mean office readings were 130.8+/-26.3/77.6+/-9.3 mm Hg, and high systolic BPs and diastolic BPs were found in 23.8% and 10% of the subjects respectively. Mean 24 h BPs were 117+/-12.5/69.7+/-7.2 (p<0.001). The normal diurnal variation in BP was now abolished in 47 (74.6%) patients (p<0.001). CONCLUSION: Survivors of stroke, both hypertensive and non-hypertensive patients, present a chronic disruption of Circadian rhythm of BP. Conventional clinical recordings are an unreliable method of controlling these patients and ABPM should be routinely performed in this population.