Circadian Rhythms of Plasma Concentrations of Na+ and K+ and Their Urinary Excretion in Normal and Diabetic Rats

The effects of streptozotocin induced diabetes (50 mg/Kg) on the circadian rhythms in the excretion of sodium and potassium as well as their plasma concentration rhythms were investigated. Control (C) and diabetic (D) rats were studied during a light-dark (12h:12h) cycle and fed ad libitum. Statistically significant circadian rhythms were found for sodium and potassium excretion in C rats. The orthophases of both rhythms occurred in the dark phase, the potassium one occurring before that of sodium. In D rats there is increased excretion of both sodium and potassium with the rhythmicity maintained for sodium excretion only, which has an earlier orthophase than in the C rats. Plasma sodium and potassium concentrations showed a statistically significant circadian pattern in C rats, with orthophase in the light phase. This rhythmicity only appears in plasma potassium concentration for D rats, with orthophase at the end of the dark phase. The results in diabetic rats may suggest that the glomerular filtration rate (GFR) and/or tubular reabsorption rhythms are still contributing to the sodium excretory rhythm, and that the loss of the circadian rhythm in sodium plasma concentration has no influence on the sodium excretion rhythm. Nevertheless, the loss of the potassium excretion rhythm may suggest a disruption of the variations in the secretory process, as this excretion seems to be independent of the plasma potassium concentration rhythm, which is not lost in D rats.     

Circadian Rhythms in Amphibians and Reptiles: Ecological Implications

Circadian rhythms of amphibians and reptiles in the field and under semi-natural conditions and the underlying mechanisms, including the ways of entrainment to environmental cues and the oscillators driving the rhythms, have been reviewed. Studies on the behavioral rhythms in the field are meager in both amphibians and reptiles. In anuran amphibians, Xenopus adults showed more robust nocturnal locomotor activity than did tadpoles. This indicates the ecological significance of the differences in activity pattern shown by amphibians at different life stages, because differences between adults and young in the same environment may serve to isolate partially the young from the adults' cannibalism. In reptiles, free-running rhythms are more robust and continue for a longer time compared to amphibians. In both amphibians and reptiles, multi-photoreceptors are involved in photo-entrainment of circadian rhythms. The eyes, pineal complex and deep brain comprise a multi-oscillator system as well as a multi-photoreceptor system.     

Assaying Locomotor Activity to Study Circadian Rhythms and Sleep Parameters in Drosophila

Most life forms exhibit daily rhythms in cellular, physiological and behavioral phenomena that are driven by endogenous circadian (≡24 hr) pacemakers or clocks. Malfunctions in the human circadian system are associated with numerous diseases or disorders. Much progress towards our understanding of the mechanisms underlying circadian rhythms has emerged from genetic screens whereby an easily measured behavioral rhythm is used as a read-out of clock function. Studies using Drosophila have made seminal contributions to our understanding of the cellular and biochemical bases underlying circadian rhythms. The standard circadian behavioral read-out measured in Drosophila is locomotor activity. In general, the monitoring system involves specially designed devices that can measure the locomotor movement of Drosophila. These devices are housed in environmentally controlled incubators located in a darkroom and are based on using the interruption of a beam of infrared light to record the locomotor activity of individual flies contained inside small tubes. When measured over many days, Drosophila exhibit daily cycles of activity and inactivity, a behavioral rhythm that is governed by the animal''s endogenous circadian system. The overall procedure has been simplified with the advent of commercially available locomotor activity monitoring devices and the development of software programs for data analysis. We use the system from Trikinetics Inc., which is the procedure described here and is currently the most popular system used worldwide. More recently, the same monitoring devices have been used to study sleep behavior in Drosophila. Because the daily wake-sleep cycles of many flies can be measured simultaneously and only 1 to 2 weeks worth of continuous locomotor activity data is usually sufficient, this system is ideal for large-scale screens to identify Drosophila manifesting altered circadian or sleep properties.     

Entrainment to Light of Circadian Activity Rhythms in Tench (Tinca tinca)

The present article analyzes locomotor activity rhythms in Tinca tinca. To that end, three different experiments were conducted on 24 animals (20 g body weight) kept in pairs in 60‐liter aquaria fitted with infrared sensors connected to a computer to continuously record fish movements. The first experiment was designed to study the endogenous circadian clock under free‐running conditions [ultradian 40:40 min LD pulses and constant dark (DD)] and after shifting the LD cycle. Our results demonstrate that tench has a strictly nocturnal activity pattern, an endogenous rhythm being evident in 45.8% of the fish analyzed. The second experiment was conducted to test the influence of different photoperiods (LD 6:18, 12:12, 18:6, and 22:2) on locomotor activity, the results showing that even under an extremely long photoperiod, tench activity is restricted to dark hours. The third experiment examined the effect of light intensity on locomotor activity rhythms. When fish were exposed to decreasing light intensities (from 300:0 lux to 30:0, 3:0, and 0.3:0 lux) while maintaining a constant photoperiod (LD 12:12), the highest percentage of locomotor activity was in all cases associated with the hours of complete darkness (0 lux). In short, our results clearly show that (a) tench is a species with a strictly nocturnal behavior, and (b) daily activity rhythms gradually entrain after shifting the LD cycle and persist under free‐running conditions, pointing to their circadian nature. However, light strongly influences activity rhythms, since (c) the length of the active phase is directly controlled by the photophase, and (d) strictly nocturnal behavior persists even under very dim light conditions (0.3 lux). The above findings deepen our knowledge of tench behavior, which may help to optimize the aquacultural management of this species, for example, by adjusting feeding strategies to their nocturnal behavior.     

Recording and Analysis of Circadian Rhythms in Running-wheel Activity in Rodents

When rodents have free access to a running wheel in their home cage, voluntary use of this wheel will depend on the time of day^1-5. Nocturnal rodents, including rats, hamsters, and mice, are active during the night and relatively inactive during the day. Many other behavioral and physiological measures also exhibit daily rhythms, but in rodents, running-wheel activity serves as a particularly reliable and convenient measure of the output of the master circadian clock, the suprachiasmatic nucleus (SCN) of the hypothalamus. In general, through a process called entrainment, the daily pattern of running-wheel activity will naturally align with the environmental light-dark cycle (LD cycle; e.g. 12 hr-light:12 hr-dark). However circadian rhythms are endogenously generated patterns in behavior that exhibit a ~24 hr period, and persist in constant darkness. Thus, in the absence of an LD cycle, the recording and analysis of running-wheel activity can be used to determine the subjective time-of-day. Because these rhythms are directed by the circadian clock the subjective time-of-day is referred to as the circadian time (CT). In contrast, when an LD cycle is present, the time-of-day that is determined by the environmental LD cycle is called the zeitgeber time (ZT).Although circadian rhythms in running-wheel activity are typically linked to the SCN clock^6-8, circadian oscillators in many other regions of the brain and body^9-14 could also be involved in the regulation of daily activity rhythms. For instance, daily rhythms in food-anticipatory activity do not require the SCN^15,16 and instead, are correlated with changes in the activity of extra-SCN oscillators^17-20. Thus, running-wheel activity recordings can provide important behavioral information not only about the output of the master SCN clock, but also on the activity of extra-SCN oscillators. Below we describe the equipment and methods used to record, analyze and display circadian locomotor activity rhythms in laboratory rodents.     

Relationship Between Orcadian Changes in Renal Hemodynamics and Circadian Changes in Urinary Glycosaminoglycan Excretion in Normal Rats

Circadian changes in renal hemodynamics and urinary glycosaminogly-can (GAG) excretion were studied in normal Sprague-Dawley rats to further investigate rhythms in kidney function. Urinary water, protein, and GAG excretion, as well as glomerular filtration rate (GFR) and renal plasma flow (RPF), were determined every 4h over the 24h cycle in an attempt to characterize any temporal changes. Urinary flow rate and proteinuria peaked during the dark activity period of the animals, consistently at the same hour, whereas the lowest values were detected during the resting phase. GAG are mucopolysaccharides entering the constitution of the glomerular basement membrane (GBM), which is the key component in the process of glomerular filtration. Similarly, the urinary excretion rate of GAG showed a circadian rhythmicity in phase with urinary water and protein excretion, with markedly increased values observed during the nocturnal phase of the animals. Moreover, GFR and RPF were demonstrated to exhibit large circadian variations in phase with renal excretory rhythmicity, showing nighttime values significantly greater compared to daytime ones. Strong correlations were found between GFR and RPF rhythms, as well as between GAG and GFR, and GAG and RPF rhythms, although the latter were not statistically significant. This pattern suggests that the circadian rhythmicity in urinary excretion rate of GAG in physiological conditions could presumably be secondary to the temporal changes in renal hemodynamics. In this respect, knowledge of renal chronobiology helpfully contributes to increase our understanding of renal physiology.     

大鼠视交叉上核与松果体中Clock基因转录的昼夜节律性及不同光反应性

本研究旨在观察和比较视交叉上核（suprachiasmatic nucleus,SCN）与松果体（pineal gland,pG）中Clock基因内源性昼夜转录变化规律以及光照对其的影响。Sprague-Dawley大鼠在持续黑暗（constant darkness,DD）和12h光照：12h黑暗交替（12hourlight：12hour-darkcycle,LD）光制下分别被饲养8周（n=36）和4周n=36）后,在一昼夜内每隔4h采集一组SCN和PG组织（n=6）,提取总RNA,用竞争性定量RT-PCR测定不同昼夜时点（circadian times．CT or zeitgeber times．ZT）各样品中Clock基因的mRNA相对表达量,通过余弦法和ClockLab软件获取节律参数,并经振幅检验是否存在昼夜节律性转录变化。结果如下：（1）SCN中Clock基因mRNA的转录在DD光制下呈现昼低夜高节律性振荡变化（P〈0．05）,PG中Clock基因的转录也显示相似的内源性节律外观,即峰值出现于主观夜晚（SCN为CTl5,PG为CT18）,谷值位于主观白天（SCN为CT3,PG为CT6）（P〉0．05）。（2）LD光制下SCN中Clock基因的转录也具有昼夜节律性振荡（P〈0．05）,但与其DD光制下节律外观相比,呈现反时相节律变化（P〈0．05）,且其表达的振幅及峰值的mRNA水平均增加（P〈0．05）,而PG中Clock基因在LD光制下转录的相应节律参数变化却恰恰相反（P〈0．05）。（3）在LD光制下,光照使PG中Clock基因转录的节律外观反时相于SCN（P〈0．05）,即在SCN和PG的峰值分别出现于光照期ZT10和黑暗期ZT17,谷值分别位于黑暗期ZT22和光照期ZT5。结果表明,Clock基因的昼夜转录在SCN和PG中存在同步的内源性节律本质,而光导引在这两个中枢核团调节Clock基因昼夜节律性转录方面有着不同的作用。     

The Effect of Old Age on the Free-Running Period of Circadian Rhythms in Rat

The free-running period is regarded to be an exclusive feature of the endogenous circadian clock. Changes during aging in the free-running period may therefore reflect age-related changes in the internal organization of this clock. However, the literature on alterations in the free-running period in aging is not unequivocal. In the present study, with various confounding factors kept to a minimum, it was found that the free-running periods for active wakefulness, body temperature, and drinking behavior were significantly shorter (by 12-17 min) in old than in young rats. In addition, it was found that the day-to-day stability of the different sleep states was reduced in old rats, whereas that of the drinking rhythm was enhanced. Transient cycles were not observed, nor were there any age-related differences in daily totals of the various sleep-wake states. The amplitudes of the circadian rhythms of active wakefulness, quiet sleep, and temperature were reduced, whereas those of paradoxical sleep and quiet wakefulness remained unchanged.     

Emphasizing Difficulties in the Detection of Rhythms with Lomb-Scargle Periodograms

The Lomb-Scargle periodogram was introduced in astrophysics to detect sinusoidal signals in noisy unevenly sampled time series. It proved to be a powerful tool in time series analysis and has recently been adapted in biomedical sciences. Its use is motivated by handling non-uniform data which is a common characteristic due to the restricted and irregular observations of, for instance, free-living animals. However, the observational data often contain fractions of non-Gaussian noise or may consist of periodic signals with non-sinusoidal shapes. These properties can make more difficult the interpretation of Lomb-Scargle periodograms and can lead to misleading estimates. In this letter we illustrate these difficulties for noise-free bimodal rhythms and sinusoidal signals with outliers. The examples are aimed to emphasize limitations and to complement the recent discussion on Lomb-Scargle periodograms.     

Circadian and Seasonal Variations of Plasma Insulin and Cortisol Concentrations in the Syrian Hamster, Mesocricetus Auratus

Circadian rhythms of plasma insulin, Cortisol, and glucose concentrations were examined in scotosensitive (reproductively sensitive to inhibitory effects of short daylengths) and scotorefractory male and female Syrian hamsters (Mesocricetus auratus) maintained on short (LD 10:14) and long (LD 14:10) daylengths. The baseline concentration (mean of all values obtained every 4 hr six times of day) of insulin was much greater in female than in male scotosensitive hamsters kept on short daylengths. These differences in insulin concentration may account for the observed heavy fat stores in female and low fat stores in male scotosensitive hamsters kept on short daylengths. The baseline concentrations of Cortisol were approximately equal in both scotosensitive and scotorefractory males held on short and long daylengths, but were relatively low in females held on short daylengths and especially high in scotorefractory females held on long daylengths.

The plasma concentrations of both cortisol and insulin varied throughout the day in many of the groups tested. However, the variations were not equivalent. The circadian variations of cortisol were similar irrespective of sex, seasonal condition and daylength. Peak concentrations generally occurred about 12 hr after light onset. In contrast, the circadian variations of insulin differed markedly. For example in male hamsters, robust daily variations were found in scotosensitive hamsters held on short daylengths but not on long daylengths and in scotorefractory hamsters held on long daylengths but not on short daylengths. Furthermore, the daily peak occurred during the light in the scotosensitive hamsters and during the dark in the scotorefractory animals. Neither the daily feeding pattern (about 60% consumed during dark) nor the daily variations of glucose concentration varied appreciably with seasonal condition or daylength. They do not appear to determine nor directly reflect the variations in cortisol and glucose concentrations. It is postulated that the daily rhythms of cortisol and insulin are regulated by different neural pacemaker systems and that changes in the phase relations of circadian systems account in part for seasonal changes in body fat stores.     

Bright Light Exposure During the Daytime Affects Circadian Rhythms of Urinary Melatonin and Salivary Immunoglobulin A

The effects of bright light exposure during the daytime on circadian urinary melatonin and salivary immunoglobulin A (IgA) rhythms were investigated in an environmental chamber controlled at a global temperature of 27°C ± 0.2°C and a relative humidity of 60% ± 5%. Seven diurnally active healthy females were studied twice, in bright and dim light conditions. Bright light of 5000 lux was provided by placing fluorescent lamps about 1 meter in front of the subjects during the daytime exposure (06:30-19:30) from 06:30 on day 1 to 10:30 on day 3. Dim light was controlled at 200 lux, and the subjects were allowed to sleep from 22:30 to 06:30 under both light exposure conditions. Urine and saliva were collected at 4h intervals for assessing melatonin and IgA. Melatonin excretion in the urine was significantly greater during the nighttime (i.e., at 06:30 on day 1 and at 02:30 on day 2) after the bright light condition than during the dim light condition. Furthermore, the concentration and the amount of salivary IgA tended to be higher in the bright light than in the dim light condition, especially during the nighttime. Also, salivary IgA concentration and the total amount secreted in the saliva were significantly positively correlated with urinary melatonin. These results are consistent with the hypothesis that bright light exposure during the daytime enhances the nocturnal melatonin increase and activates the mucosal immune response.     

Chronic Administration of Imipramine and Lithium Changes the Phase-Angle Relationship Between the Activity and Core Body Temperature Circadian Rhythms in Rats

Evidence suggests that there is an association between the pathophysiology of depression and a disturbance of circadian rhythms. Accordingly, attention has focused on the possible effects of antidepressants on circadian rhythms. In the present study, we examined the effects of chronic administration of two clinically effective antidepressant agents, imipramine and lithium, on several circadian rhythms in the rat. Activity, core body temperature, and drinking rhythms were assessed in constant darkness (DD) and light-dark (LD) conditions. In DD, lithium significantly lengthened the circadian period of the activity, temperature, and drinking rhythms, while imipramine had no effect. In LD, both drugs significantly delayed the phase of the activity rhythm, but did not change that of the other two rhythms. As a result, the phase-angle differences between the activity and temperature rhythms significantly increased. Neither lithium nor imipramine produced any effect on the resynchronization of these rhythms after an 8-h delay in the LD cycle. These results indicate that although both drugs produced different effects on the circadian period of individual rhythms, both caused a relative phase advance of the temperature rhythm as compared to the activity rhythm, and this effect may be related to the similarity in their antidepressant effects. (Chronobiology International, 13(4), 251-259, 1996)     

Effect of Continuous Infusion of Anti-L1 Antibody into the Third Cerebral Ventricle above the Suprachiasmatic Nucleus on the Circadian Rhythm of Locomotor Activity in Rats

During an investigation into the role of the neural cell adhesion molecules such as L1 and NCAM in the generation mechanism of circadian rhythms, we observed that L1-like immunoreactive substance is expressed in the hypothalamic suprachiasmatic nucleus (SCN). Therefore, we examined the effect of continuous infusion of anti-L1 antibody into the third cerebral ventricle above the SCN using an Alzet osmotic minipump, on the circadian rhythm of locomotor activity in rats under constant red dim light (less than 1 lx) condition, in order to elucidate the role of L1 in the mechanism of circadian rhythm. Continuous infusion of intact rabbit IgG into the third cerebral ventricle above the SCN, which was done as a control experiment, shifted the phase of the free-running circadian rhythm and reduced daily locomotor activity for an initial few days, however, it did not eliminate the circadian rhythm. In contrast, continuous infusion of anti-L1 antibody temporarily disrupted the circadian rhythm during the infusion period. Furthermore, the infusion of the anti-L1 antibody but not that of control IgG caused a change in the SCN conformation, from which it appeared that SCN neurons displaced in dorsal direction, 4 days after the start of the infusion. These findings suggest that the cell adhesion molecule, L1, might be involved in the generation and/or transduction of the time signal of the circadian rhythm in the SCN.     

Light and Temperature Cycles as Zeitgebers of Zebrafish (Danio rerio) Circadian Activity Rhythms

Light and temperature cycles are the most important synchronizers of biological rhythms in nature. However, the relative importance of each, especially when they are not in phase, has been poorly studied. The aim of this study was to analyze the entrainment of daily locomotor activity to light and/or temperature cycles in zebrafish. Under two constant temperatures (20°C and 26°C) and 12:12 light-dark (LD) cycles, zebrafish were most active during the day (light) time and showed higher total activity at the warmer temperature, while diurnalism was higher at 20°C than at 26°C (87% and 77%, respectively). Under thermocycles (12:12 LD, 26:20°C thermophase:chryophase or TC), zebrafish daily activity synchronized to the light phase, both when the thermophase and light phase were in phase (LD/TC) or in antiphase (LD/CT). Under constant dim light (3 lux), nearly all zebrafish synchronized to thermocycles (τ=24 h), although activity rhythms (60% to 67% of activity occurred during the thermophase) were not as marked as those observed under the LD cycle. Under constant dim light of 3 lux and constant temperature (22.5°C), 4 of 6 groups of zebrafish previously entrained to thermocycles displayed free‐running rhythms (τ=22.9 to 23.6 h). These results indicate that temperature cycles alone can also entrain zebrafish locomotor activity.     

Circadian Rhythms of Circulating NK Cells in Healthy and Human Immunodeficiency Virus-Infected Men

Antiviral immunity involves NK cells, which circulate rhythmically every 24 hours. We have investigated circadian and 12-hour rhythms in the peripheral count of circulating NK cells in 15 men infected with human immunodeficiency virus (HIV) and 13 healthy controls. We analyzed three phenotypes using double-labeling with monoclonal antibodies and flow cytometry assessment: CD3^? CD16⁺, CD3^?CD57⁺, and CD2⁺CD3^?. A statistical validation of time-dependent differences was achieved if significance (p < 0.05) was validated both with analysis of variance and cosinor. The circadian rhythm had a similar asymmetric waveform for the three phenotypes and is homogeneous on an individual basis. The circulating NK cell count peaked in the early morning and was low at night. A circadian rhythm and a circahemidian harmonic characterized all phenotypes in healthy subjects. We considered two groups of HIV-infected men: those who were asymptomatic (eight) and those with acquired immune deficiency syndrome (AIDS) (seven). Circadian changes in NK cell count were similar in both subgroups and in healthy controls. The circadian pattern was also consistent among individual patients. Asymptomatic HIV-infected men (early-stage disease) exhibited more pronounced 12-hour rhythmicity than did patients with AIDS or controls. The circulation of NK cells does not appear to share the same synchro-nizer(s) as other circulating T- or B-lymphocyte subsets. Thus, HIV infection gradually abolished circadian rhythmicity in circulating T and B cells, whereas it did not disturb that in NK cells.     

Sleep and Circadian Rhythms of Temperature and Urinary Excretion on a 22.8 hr “Day”

Two groups of subjects (total N = 6) were studied in an isolation chamber for a period of 3 weeks whilst living on a 22.8 hr “day”. Regular samples of urine were taken when the subjects were awake, deep body temperature was recorded continuously and polygraphic EEG recordings were made of alternate sleeps. The excretion in the urine of potassium, sodium, phosphate, calcium and a metabolite of melatonin were estimated.

Measurements of the quantity and quality of sleep were made together with assessments of the temperature profiles associated with sleep. In addition, cosinor analysis of circadian rhythmicity in urinary variables and temperature was performed.

The 22.8 hr “days” affected variables and subjects differently. These differences were interpreted as indicating that the endogenous component of half the subjects adjusted to the 22.8 hr “days” but that, for the other three, adjustment did not occur. When the behaviour of different variables was considered then some (including urinary potassium and melatonin, sleep length and REM sleep) appeared to possess a larger endogenous component than others (for example, urinary sodium, phosphate and calcium), with rectal temperature behaving in an intermediate manner. In addition, a comparison between different rhythms in any subject enabled inferences to be drawn regarding any links (or lack of them) that might exist between the rhythms. In this respect also, there was a considerable range in the results and no links between any of the rhythms appeared to exist in the group of subjects as a whole.

Two further groups (total N=8) were treated similarly except that the chamber clock ran at the correct rate. In these subjects, circadian rhythms of urinary excretion and deep body temperature (sleep stages and urinary melatonin were not measured) gave no evidence for deterioration. We conclude, therefore, that the results on the 22.8 hr “day” were directly due to the abnormal “day” length rather than to a prolonged stay in the isolation chamber.     

Effect of Beer Ingestion on the Plasma Concentrations and Urinary Excretion of Purine Bases: One-Month Study

To investigate the effect of long-term beer ingestion on the plasma concentrations and urinary excretion of purine bases, 5 healthy males participated in the present study, during which they ingested beer every evening for 30 days. Blood and 24-hour urine samples were collected in the morning one day before and 14 and 30 days after the initiation of the beer ingestion. During the beer ingestion period, the plasma concentration and the urinary excretion of uric acid were increased significantly, while uric acid clearance was not decreased. Further, purine ingestion was not significantly different throughout the study. These results suggest that production of uric acid by ethanol ingestion was the main contributor to the increased plasma uric acid. Therefore, patients with gout should be encouraged to avoid drinking large amounts of beer on a daily basis.     

Forced Desynchrony of Orcadian Rhythms of Body Temperature and Activity in Rats

The daily rhythm in body temperature is thought to be the result of the direct effects of activity and the effects of an endogenous circadian clock. Forced desynchrony (FD) is a tool used in human circadian rhythm research to disentangle endogenous and activity-related effects on daily rhythms. In the present study, we applied an FD protocol to rats. We subjected 8 rats for 5 days to a 20h forced activity cycle consisting of lOh of forced wakefulness and lOh for rest and sleep. The procedure aimed to introduce a lOh sleep/ lOh wake cycle, which period was different from the endogenous circadian (about 24h) rhythm. Of the variation in the raw body temperature data, 68-77% could be explained by a summation of estimated endogenous circadian cycle and forced activity cycle components of body temperature. Free-running circadian periods of body temperature during FD were similar to free-running periods measured in constant conditions. The applied forced activity cycle reduced clock-related circadian modulation of activity. This reduction of circadian modulation of activity did not affect body temperature. Also, the effects of the forced activity on body temperature were remarkably small.     

The Circadian Rhythm of Plasma Thyrotropin in Depression and Recovery

The 24-hr patterns of plasma thyrotropin have been observed in 12 endogenous depressed patients in both depressed and recovered states and in 13 normal subjects. A clear circadian rhythm was detected in controls with high values at night. In depression, the circadian rhythm was altered with amplitude reduction and blunted nocturnal secretion, abnormalities particularly relevant in bipolar patients. This flattened profile could be linked to the blunted response of TSH to TRH administration reported in depressed patients. Normal nyctohemeral patterns have been restored after recovery. These chronobiological abnormalities as well as their normalization under antidepressant drugs seem to be similar to those reported for various parameters (e.g. temperature, Cortisol, etc) in depression which could support the chronobiological hypothesis for affective disorders.     

The Circadian Rhythm of Plasma Thyrotropin in Depression and Recovery

The 24-hr patterns of plasma thyrotropin have been observed in 12 endogenous depressed patients in both depressed and recovered states and in 13 normal subjects. A clear circadian rhythm was detected in controls with high values at night. In depression, the circadian rhythm was altered with amplitude reduction and blunted nocturnal secretion, abnormalities particularly relevant in bipolar patients. This flattened profile could be linked to the blunted response of TSH to TRH administration reported in depressed patients. Normal nyctohemeral patterns have been restored after recovery. These chronobiological abnormalities as well as their normalization under antidepressant drugs seem to be similar to those reported for various parameters (e.g. temperature, Cortisol, etc) in depression which could support the chronobiological hypothesis for affective disorders.