Circadian Parameters Research Articles

Relationship between physical activity and blood pressure in dipper and non-dipper hypertensive patients.

The lack of nocturnal decline in blood pressure has been associated with an increase in end-organ damage and cardiovascular events, although results remain controversial, partly because of the inability to reproduce correctly, over time, the classification of patients into dippers and non-dippers. Moreover, the non-dipping status has been frequently related to an increase in nocturnal activity, differences in quality of sleep, or both. To assess the relationship between activity and blood pressure in patients with hypertension. We studied 306 mild-to-moderately hypertensive patients (130 men), 53.7 +/- 14.0 years of age (mean +/- SD). Blood pressure and heart rate were measured for 48 consecutive hours, at 20-min intervals during the day and at 30-min intervals at night, using an ambulatory device, and physical activity was simultaneously evaluated at 1-min intervals by wrist actigraphy. Circadian parameters of blood pressure, heart rate and activity established by population multiple-components analysis were compared between dippers and non-dippers, by non-parametric testing. Diurnal and nocturnal means of blood pressure and activity were computed for each patient according to individual resting hours determined by actigraphy, and compared among groups by analysis of variance. Despite highly statistically significant differences between dippers and non-dippers with respect to nocturnal means and in each hourly nightly mean of blood pressure, there were no differences between them for the same parameters during activity, whether or not the patients were receiving medication at the time of monitoring. The average duration of sleep and the 24-h mean and standard deviation of activity were also similar between the groups. The highly significantly different circadian variation in blood pressure between dippers and non-dippers with essential hypertension is not related to a significant increase in nocturnal physical activity. Differences in blood pressure could, however, be related to the absence of 24-h therapeutic coverage in most non-dipper patients receiving antihypertensive medication.

Changes in ambulatory monitored blood pressure after suppression of alcohol consumption in untreated hypertensive patients

Previous epidemiological studies have shown a positive correlation between blood pressure (BP) and alcohol consumption, independently of age, gender, ethnic origin, or obesity. Some prospective studies have also shown a pressor effect of alcohol both in normotensive as well as hypertensive subjects [Potter et al. Hypertension. 1986;8:625-631. Abe et al. Circulation. 1994;89:2626-2633]. The aim of this study was to evaluate the effects of suppression of alcohol consumption on the circadian pattern of BP determined by ambulatory monitoring (ABPM) in untreated hypertensive patients. We studied 40 patients (21 men; age 52.8±4.9 years) with mild essential hypertension. Alcohol intake was assessed by questionnaire and expressed in g/day. Moderate drinkers (<80 g/day) were excluded. After their initial clinical evaluation including 24-hour ABPM, patients followed hygienic-dietary recommendations, including suppression of alcohol intake. After 3 months, patients were evaluated again by ABPM and quantification of alcohol consumption. The circadian pattern of BP in each group (drinkers, n=13; ex-drinkers, n=13; non-drinkers, n=14) was established by population multiple-component analysis [Fernandez & Hermida. Chronobiol Int. 1998;15:191-204]. Circadian parameters obtained for each group before and after intervention were compared by nonparametric paired testing. After 3 months of hygienic-dietary recommendations there was a statistically significant reduction for the non-drinkers in the 24-hour mean of systolic BP (5.0 mm Hg; P=0.002), as well as in the daily mean of systolic (3.2 mm Hg; P<0.001) and diastolic BP (2.3 mm Hg; P=0.042) for the ex-drinkers. This group was also characterized by a statistically significant reduction in standard deviation (P=0.027), as well as in circadian amplitude of BP (P=0.020), due to the reduction in the diurnal mean and the increase in the nocturnal mean of BP after alcohol suppression. There was no significant change in circadian parameters of BP in the group of drinkers who continued consuming alcohol above 80 g/day. Suppression of alcohol consumption in conjunction with other hygienic-dietary recommendations was effective in lowering BP and its variability in untreated hypertensive patients who regularly consumed alcohol (>80 g/day).

REGULATION OF THE 24H BODY TEMPERATURE RHYTHM OF WOMEN IN LUTEAL PHASE: ROLE OF GONADAL STEROIDS AND PROSTAGLANDINS

An investigation into whether the rise in the 24h body temperature rhythm observed in the luteal menstrual phase is antagonized by the administration of prostaglandin synthesis inhibitors has been made. Intravaginal body temperature was monitored continuously for 24 h, once in the follicular and twice in the luteal phase. In the luteal phase, women were studied both without and with the simultaneous administration of a prostaglandin synthesis inhibitor (lysine acetylsalicylate; 1.8 g every 6 h orally). The progesterone/estradiol ratio (measured at 17:00h each day) was related to mesor (r=0.825; P<0.001), acrophase (r=0.682; P<0.02), and amplitude (r=−0.731; P<0.001) of the 24h body temperature rhythm. Luteal phase elevation of the progesterone/estradiol ratio was associated with a 0.32±0.07°C increase in mesor (P<0.01), a 0.11±0.02°C decrease in amplitude (P<0.001), and a 34.8±11.6 min delay in acrophase (P<0.03) of the 24h body temperature rhythm. Prostaglandin synthesis inhibitors did not counteract these modifications. The present data shows that the modifications of the circadian parameters of the 24h body temperature rhythm observed during the luteal phase of the menstrual cycle are strictly related to modifications of the progesterone/estradiol ratio, and presumably independent of prostaglandin synthesis.

Influence of parity and age on ambulatory monitored blood pressure during pregnancy.

Studies based on casual blood pressure measurements concluded that both age and parity have significant effects on blood pressure during pregnancy. We have tested these results on clinically healthy normotensive women who were systematically studied by ambulatory blood pressure monitoring during their pregnancies. We analyzed 1254 blood pressure series sampled for 48 consecutive hours every 4 weeks from the first obstetric visit (usually within the first trimester of pregnancy) until delivery in 205 normotensive pregnant women. Data were divided for comparative analysis by parity (nulliparous versus multiparous), age (</=25, 26 to 30, 31 to 35, and >/=36 years), and trimester of gestation. Circadian parameters established by population multiple-component analysis were compared between groups with a nonparametric test. Effects of age and parity on blood pressure were also tested by ANOVA. A highly statistically significant circadian pattern described by a model that includes components with periods of 24 and 12 hours is demonstrated for systolic and diastolic blood pressure for all groups of pregnant women in all trimesters (always P<0.001). There was no significant difference in 24-hour mean among groups divided by parity at any age or stage of pregnancy (always P>0.160). A trend of increasing blood pressure with age was found for diastolic but not systolic blood pressure. Although statistically significant, differences in the 24-hour mean of diastolic blood pressure among groups divided by age were always <1.5 mm Hg. Data obtained from systematic ambulatory monitoring in normotensive pregnant women indicate the lack of differences in blood pressure according to parity. The small, although significant, increase in diastolic blood pressure with age may have little influence in the proper identification of women with gestational hypertension. Reference thresholds for blood pressure to be used in the early identification of hypertensive complications in pregnancy could thus be developed as a function of rest-activity cycle and gestational age, independent of parity or maternal age.

DOES THE DIFFERENCE IN THE TIMING OF ECLOSION OF THE FRUIT FLY DROSOPHILA MELANOGASTER REFLECT DIFFERENCES IN THE CIRCADIAN ORGANIZATION?

The eclosion rhythm of a laboratory population of Drosophila melanogaster was studied under 12h light, 12h dark (LD 12:12) cycles. Although most of the flies were found to eclose just after “lights on” in LD 12:12, termed within gate (WG) flies, a few flies were found to eclose nearly 10h after peak eclosion, termed outside gate (OG) flies. The circadian parameters of the clocks controlling oviposition rhythms in the WG and the OG flies were estimated to understand the cause of such differences in the timing of eclosion. The distribution of the fraction of individual flies exhibiting single, multiple, and no significant period in the WG flies was significantly different from distribution in the OG flies. Compared to the WG flies, more OG flies were found to exhibit oviposition rhythm with multiple periodicity, whereas more WG flies exhibited an oviposition rhythm with a single significant period. The fraction of flies with arrhythmic oviposition was similar in both the WG and the OG flies. Free-running period τ in constant darkness (DD) and the phase angle difference ψ in LD 12:12 for the oviposition rhythm of WG and OG flies were significantly different. These results suggest that the differences in the time of eclosion between the flies eclosing within the gate and outside the gate of eclosion are probably due to differences in the circadian system controlling eclosion, which is reflected by the differences in their oviposition rhythm. (Chronobiology International, 18(4), 601–612, 2001)

CONTRIBUTION OF CIRCADIAN PHYSIOLOGY AND SLEEP HOMEOSTASIS TO AGE-RELATED CHANGES IN HUMAN SLEEP

The circadian pacemaker and sleep homeostasis play pivotal roles in vigilance state control. It has been hypothesized that age-related changes in the human circadian pacemaker, as well as sleep homeostatic mechanisms, contribute to the hallmarks of age-related changes in sleep, that is, earlier wake time and reduced sleep consolidation. Assessments of circadian parameters in healthy young (∼20–30 years old) and older people (∼65–75 years old)—in the absence of the confounding effects of sleep, changes in posture, and light exposure—have demonstrated that an earlier wake time in older people is accompanied by about a 1h advance of the rhythms of core body temperature and melatonin. In addition, older people wake up at an earlier circadian phase of the body temperature and plasma melatonin rhythm. The amplitude of the endogenous circadian component of the core body temperature rhythm assessed during constant routine and forced desynchrony protocols is reduced by 20–30% in older people. Recent assessments of the intrinsic period of the human circadian pacemaker in the absence of the confounding effects of light revealed no age-related reduction of this parameter in both sighted and blind individuals. Wake maintenance and sleep initiation are not markedly affected by age except that sleep latencies are longer in older people when sleep initiation is attempted in the early morning. In contrast, major age-related reductions in the consolidation and duration of sleep occur at all circadian phases. Sleep of older people is particularly disrupted when scheduled on the rising limb of the temperature rhythm, indicating that the sleep of older people is more susceptible to arousal signals genernpated by the circadian pacemaker. Sleep-homeostatic mechanisms, as assayed by the sleep-deprivation–induced increase of EEG slow-wave activity (SWA), are operative in older people, although during both baseline sleep and recovery sleep SWA in older people remains at lower levels. The internal circadian phase advance of awakening, as well as the age-related reduction in sleep consolidation, appears related to an age-related reduction in the promotion of sleep by the circadian pacemaker during the biological night in combination with a reduced homeostatic pressure for sleep. Early morning light exposure associated with this advance of awakening in older people could reinforce the advanced circadian phase. Quantification of the interaction between sleep homeostasis and circadian rhythmicity contributes to understanding age-related changes in sleep timing and quality. (Chronobiology International, 17(3), 285–311, 2000)

A New Concept for Melatonin Deficit: On Pineal Calcification and Melatonin Excretion

Even though exogenous melatonin has proven to influence sleep and circadian parameters, low endogenous melatonin is not related to sleep disturbances, nor does it predict response to melatonin replacement therapy. In this manuscript, we present a new concept towards a definition of a melatonin deficit. The purpose of the study was to introduce a marker for an intra-individual decrease in melatonin production. Therefore, we developed a method to quantify the degree of pineal calcification (DOC) using cranial computed tomography. Combining pineal DOC with the organs's size, we estimated the uncalcified pineal gland volume. This estimation was positively and significantly associated with 6-sulfatoxymelatonin (aMT6s), collected over 24 hours in urine, in 26 subjects. Data yielded evidence that the decline in aMT6s excretion with age can be sufficiently explained by an increased pineal calcification. These results suggest that DOC might be useful as an indicator of an intra-individual, decreased capability of the pineal gland to produce melatonin. DOC might prove to be a response-marker for melatonin replacement therapy and a vulnerability marker of the circadian timing system.

Obsessive-compulsive disorder: evaluation of clinical and biological circadian parameters during fluoxetine treatment.

Many biological abnormalities have been found in obsessive-compulsive disorder (OCD). The circadian rhythm investigations of different clinical and biological parameters may provide a comparison with depression. Fluoxetine is one of the efficient drugs in alleviating symptoms of OCD. The effect of fluoxetine can highlight some clues to the neurotransmitter alterations in the disorder. The present study investigated clinical and biological circadian modifications in OCD patients during a fluoxetine treatment. Daily clinical symptoms, and circadian rhythms of axillary temperature, plasma cortisol and plasma melatonin were assessed in eight patients suffering from OCD. These parameters were compared in the same patients, before and after an 8-week fluoxetine treatment period. A therapeutic effect of fluoxetine was obtained. No significant differences were observed either in daily clinical variations or in biological circadian rhythms measured before and after treatment. The therapeutic efficacy of fluoxetine was not related to the biological parameters assessed.

Circadian parameters as individual characteristics.

Human circadian rhythms that are free running in temporal isolation can show an extreme variability of the sleep-wake cycle without the subject being aware of it. This is due mainly to a systematic adjustment of certain circadian time structures to the varying length of the "day": the perception of long time intervals in the range of 1 h and the intervals between meals have a strong positive correlation with the duration of wake time alpha, in contrast to the amount of hourly locomotor activity that is negatively correlated with alpha. So far, the dependence of locomotor activity, of the "1-h" intervals, and of the intermeal intervals on alpha is well documented for the data sets of single subjects. The present article demonstrates that the correlations found intraindividually also apply if data from several subjects are compared. If plotted as a function of the mean individual alpha, the individual means of "1-h" intervals and of the intermeal intervals show the same positive correlation and the means of locomotor activity show the same negative correlation with alpha as known from single individuals. It is to be concluded that each individual has its characteristic place on the regression lines that describe the dependence of the three circadian parameters on the duration of wake time.

A follow-up study of actigraphic measures in home-residing Alzheimer's disease patients.

This article reports cross-sectional and follow-up data with actigraphic measures of nocturnal sleep and rest/activity in 61 Alzheimer's disease (AD) patients as well as the relation of actigraphic measures to levels of behavioral disturbance across different stages of the disease. Over the course of approximately 1.5 years' follow-up, patients showed significant deterioration of nocturnal sleep parameters, but no significant change in rest/activity circadian rhythm parameters. There were also significant correlations among nocturnal sleep, rest/activity circadian rhythm, and behavioral disturbance measures, but only in relatively early stages of AD. It is argued that study of nocturnal sleep and circadian rhythm in relation to behavioral disturbance in AD requires longitudinal data and analyses that take into account the stage of disease at which patients are assessed.

Malate Dehydrogenase Activity of Rat Testis: Circadian Rhythm and its Ontogeny

Malate dehydrogenase activity and soluble protein content in testes from rats exposed to a 14:00 h light:10:00 h dark photoperiod, have been determined every two or four hours over a 24 hour period in 5, 15, 25 and 120 day-old rats. By using the Cosinor method, the ontogeny of an unimodal rhythm was studied for MDH activity and soluble protein content in testis. In 5 and 15 day-old rats, the MDH acrophases were recorded around 19:00 h and 17:00 h, respectively. Rats aged 25 and 110 days showed the MDH acrophases during the dark period. An inversion of the MDH circadian rhythms was detected in 25 day-old compared to those of 5 and 15 day-old rats. An inversion of the protein circadian rhythm was also detected at 15 days compared to that at 5 days. These inversions persist in the adult rats. The amplitude of the MDH and protein rhythms reached the lowest value in adulthood. The mean daily value of testicular MDH increased between day 5 and 15, decreasing at day 35 and remaining unchanged until adulthood. The variation of malate dehydrogenase activity, soluble protein content levels, and the circadian rhythm parameters during the maturation process may be related to gonad development.

Blood Pressure Circadian Rhythm and Variability in Subjects with Severe Heart Failure

To explore whether a condition of severe heart failure results in alteration of the 24-h-blood pressure (BP) profile and BP circadian rhythm, 19 patients with severe heart failure (NYHA class III-IV, 17M, 2F, mean age 57+/-8 years) were considered and compared to a control group of age- and sex-matched normal subjects. All subjects were submitted to non-invasive 24-h ambulatory blood pressure monitoring using a SpaceLabs 90207 unit (recording interval 15 min). Both systolic and diastolic BP profiles were evaluated using the two-step method of analysis reported by Staessen: the existence of a BP circadian rhythm was first tested using Siegel's runs test, then a Fourier multiple harmonic analysis allowed us to obtain the BP profile parameters Acrophases (Acro, hh:mm) and Amplitudes (Ampl, mm Hg). The same methods were used for pulse rate. Our results showed the presence of a BP circadian rhythm in severe heart failure subjects, as well as in control subjects. Furthermore, no significant difference was found between the two groups when considering the BP profile parameters Acro and Ampl. In conclusion, in contrast with previous reports, our results show that both BP circadian rhythm and BP profile parameters are preserved in patients with severe heart failure.

Effects of Complete and Skeleton Photoperiods on the Circadian Rhythm of the Electroretinogram of the Crayfish

Applying complete photoperiods (PPc), with photophases that varied from 4 to 20 h of the 24-h cycle, we studied entrainment of the circadian rhythm of the electroretinogram (ERG) of crayfish by external light signals. All the PPc regimens tested synchronized the rhythm, which adjusted its circadian period to exactly 24 h; the duration of the photophase affected only other circadian parameters, such as the activity level and the ratio of the duration of active to resting phases. Entrainment of the ERG by skeleton photoperiods (PPs) was also studied. All the PPs tested (each PPs corresponded to a specific PPc regimen) also entrained the ERG rhythm. The use of PPs revealed that the bistability zone of the rhythm lay between light-dark (LD) 11:13 and LD 13:11. When the interval of darkness between the periods of illumination during PPs became less than 11 h, the circadian rhythm of the ERG exhibited a “jump” phase in which the maximal activity period jumped to the period of longer darkness; this result implies that the crayfish requires a minimum tolerable night.

The Effects of Mixing on Behavior and Circadian Parameters of Salivary Cortisol in Pigs

Ekkel, E. D., B. Savenije, W. G. P. Schouten, V. M. Wiegant and M. J. M. Tielen. The effects of mixing on behavior and circadian parameters of salivary cortisol in pigs. Physiol Behav 62(1) 181–184, 1997.—The present study describes an experiment that was carried out to study the effects of mixing pigs once at 25 kg, preceded by transportation for 1.5 h, on the behavior and the circadian rhythmicity of salivary cortisol. The frequency of agonistic interactions was higher for mixed pigs. This was not only the case immediately after mixing, when pigs started to fight to establish a new social rank (p < 0.05), but also 5 to 6 weeks later; still more headknocks and bites towards other pigs were seen at that time among mixed pigs (p < 0.01). However, neither the basal cortisol concentration, assessed as the MESOR of the circadian rhythm of salivary cortisol, nor the amplitude of that rhythm was different between the groups.

An Approach to Studying Circadian Rhythms of Adolescent Humans

The "long nights" protocol was designed to evaluate sleep processes and circadian rhythm parameters in young humans. A total of 19 children (10 boys, ages 11.2 to 14.1 years [mean = 12.7 +/- 1.0], and 9 girls, ages 12.2 to 14.4 years [mean = 13.1 +/- 0.7]) took part in the study. Sleep/wake initially was assessed at home using actigraphy and diary for 1 week on each child's self-selected schedule followed by an 8-night fixed light-dark (LD) condition, while sleeping from 22:00 to 08:00 h and wearing an eye mask to exclude as much light as possible. Phase measurements included 4-night mean actigraphically estimated sleep onset and offset as well as 1-night dim light salivary melatonin onset (DLSMO) phase at the end of each condition. Subjects then lived in the laboratory for 6 consecutive cycles: Day 1 LD = 14:10 h, lights out 22:00 to 08:00 h; Days 2-4 LD = 6:18 h, lights out 18:00 to 12:00 h; Days 5-6 = constant routine in continuous dim light (about 20 lux); Night 6 = 14 h recovery sleep. Phase markers (sleep onset, sleep offset, DLSMO) were significantly less dispersed after the fixed LD as compared to the self-selected condition, indicating efficacy of the LD protocol. Phase markers were correlated at the self-selected assessment (sleep onset vs. sleep offset r = .72; DLSMO vs. sleep onset r = .82; DLSMO vs. sleep offset r = .76) but not on the fixed schedule, probably due to restricted range. The constant routine provided additional phase markers, melatonin offset and midphase. Offset phase of melatonin secretion was significantly correlated with age (r = .62) and Tanner stage (r = .62). In conclusion, these preliminary data indicate a relationship between adolescent development and circadian phase. Thus, the long nights protocol is a feasible way in which to assess circadian parameters in young humans as well as to examine intrinsic sleep processes.

Geographical and species variation in circadian rhythm parameters in nemobiine crickets

Abstract. . Locomotor activity rhythms were studied in eight species of nemobiine crickets with different habitat preferences. They showed similar patterns with a major peak of activity around dusk and a minor one around dawn. These patterns did not change within the natural range of daylengm (12–16 h). The acrophase time of the rhythm varied between ‐3.2 and +3.5 h as measured from dusk, and the free‐running period (T) varied between 22.8 and 24.5 h. In the Dianemobius fascipes species complex these circadian parameters varied among nine local strains (8oS to 43oN) but did not show any latitudinal trend. In a temperate strain of this species complex (Dianemobius nigrofasciatus from Teshikaga, 43oN), two lines which differed from each other in mean T by 1.4h were selected, and a high heritability of T, 0.78 + 0.20 (mean±SE) was obtained. On the other hand, in a subtropical strain (Dianemobius fascipes from Ishigaki Island, 24oN), low heritabilities, 0.35 ± 0.15 for acrophase and 0.17 ± 0.21 for T, were obtained from the full‐sib correlations. The variation in i seemed to be random and not related to fitness.

Blood Pressure Circadian Rhythm and Variability in Essential Hypertensives without End-organ Damage

The aim of the study was to evaluate the 24-hour Blood Pressure (BP) profile in essential hypertensives without end-organ damage using a two-step method proposed by Staessen and his group: the existence of a circadian rhythm is first tested using Siegel’s Runs-Test, then a Fourier multiple harmonic analysis allows an adequate parametrical representation of the 24-hour BP profile. Sixty-five newly diagnosed, untreated mild-to-moderate essential hypertensives without end-organ damage (HYP) were compared to 29 normal control subjects (NORM). No significant differences have been found between the two groups when considering the existence of a BP circadian rhythm and acrophase parameters, as distinct from amplitudes (p<0.01). Furthermore, as expected, BP mean values were found higher in the HYP group as compared with the NORM group. In conclusion, according to our results, essential hypertensives without end-organ damage present a preserved BP profile, showing a circadian rhythm, but, as compared to normal subjects, increased BP variability (BPV) as expressed by amplitude values. The present study is consistent with the hypothesis that BPV, even though related, is not a consequence of end-organ damage.

Food Intake and Circadian Rhythms of Activity of Red-Winged Blackbirds (Agelaius phoeniceus). A Time-Course Study on the Effects of Alpha-Chloralose and Secobarbital

Anesthetic drugs like alpha-chloralose and secobarbital are used to capture wild birds. The doses are usually chosen on the basis of low mortality rates and high capture success. However, little information is available on the time necessary for the birds to fully recover from the drugs' effects after they have regained consciousness. In this work, we used circadian rhythms of activities to study the long-term effects of a mixture of alpha-chloralose and secobarbital on adult male Red-winged Blackbirds. The birds were housed individually in sound-proof boxes for 30 days, during which they received alpha-chloralose and secobarbital mixed with corn, either on day 3 or on day 15. On the day of treatment, the birds experienced a significant decrease in activity level, including feeding activities, which lasted more than 22 days for the birds treated on day 3, compared to about 8 days for the birds treated on day 15. Moreover, typical circadian distribution of activity was lost and many birds became aperiodic. Two weeks were needed for the birds treated on day 3 to recover normal rhythms, compared to less than 9 days for those treated on day 15. These results indicate that circadian parameters can be used to detect after-effects of intoxication long after the birds have regained consciousness.

Circadian variation of growth hormone secretion in normal prepubertal children. Comparison to constitutional growth delay and growth hormone deficiency

When studying short slowly growing children, several investigators have found differences in spontaneous circulating growth hormone (GH) levels in some short children as compared with children of normal stature. The circadian and ultradian characteristics of GH secretion have not been considered in most of those studies. With the aim to study possible differences in rhythm characteristics of plasma GH with stature, we analyzed data from a total of 141 prepubertal children: 1) 13 GH-deficient children; 2) 36 children with short stature (up to 2 standard deviations below their peer group mean); 3) 61 children with very short stature (up to 4 standard deviations below their peer group mean); and 4) a reference group of 31 children with standard stature. Subjects were living at the hospital setting on a diurnal waking (07:30 a.m. to 10:30 p.m.), nocturnal resting routine during sampling, consuming the usual hospital diet at fixed times. GH concentrations were determined by immunoradiometric assay in plasma obtained at about 2-3 hour intervals during most of the day and at about half-hour intervals between 9:00 p.m. and 3:00 a.m. Circadian rhythm characteristics obtained by least-squares estimation were compared between groups divided according to gender and stature with a parameter test. Results show a statistically significant circadian rhythm in GH secretion for all groups studied (p<0.001 for standard, short and very short children; p=0.013 for GH-deficient children). A comparison of circadian parameters indicates similar characteristics between subjects of short, very short and standard stature. The difference in rhythm-adjusted mean and amplitude is, however, of borderline statistical [correction of statistically] significance when comparing non-deficient with GH-deficient children.

Differential serotonergic innervation of the suprachiasmatic nucleus and the intergeniculate leaflet and its role in circadian rhythm modulation

Serotonergic innervation is believed to inhibit the effects of light on the mammalian circadian timing system. Two anatomical components of this system, the suprachiasmatic nucleus (SCN) and the intergeniculate leaflet (IGL), receive serotonergic input from midbrain raphe nuclei. The present studies use retrograde and anterograde tracing as well as neurotoxic lesion techniques to demonstrate that serotonergic cells in the median raphe nucleus (MR) project to the SCN and that serotonergic cells in the dorsal raphe nucleus (DR) project to the IGL. Neurotoxic lesions were also used to investigate the effects of selective serotonin (5-HT) neuron loss in the MR or DR on circadian rhythm parameters of animals entrained to a light/dark cycle or housed in constant light. 5-HT depletion in the MR, but not in the DR, induces an advance in onset, a delay in offset, and a longer duration of the nocturnal running-wheel activity phase. Circadian rhythm disruption in constant light is also more frequent in hamsters with MR lesions. A second experiment was designed to investigate the relationship between lesion location, 5-HT-immunoreactive (5-HT-IR) fiber loss, and behavioral changes. Destruction of 5-HT neurons in the MR causes 5-HT-IR fiber loss in the SCN, which may account for the observed changes in circadian parameters. DR lesions result in 5-HT-IR fiber depletion of the IGL, with no associated changes in the entrained rhythm. The anatomical and behavioral results support the view that a 5-HT projection from the MR mediates 5-HT effects on circadian rhythm regulation in hamsters.