Panic and panic disorder in the United States

OBJECTIVES: Shift work and rapid travel across several time zones leads to desynchronization of internal circadian rhythms from the external environment and from each other with consequent problems of behaviour, physiology and performance. Field studies of travellers and shift workers are expensive and difficult to control. This investigation concerns the simulation of such rhythm disturbance in a laboratory environment. The main objectives are to assess the ability of controlled exposure to moderately bright light and darkness/sleep to delay circadian rhythms in volunteers without environmental isolation and, secondly, to evaluate the use of different indices of melatonin (MT) secretion together with self-rated alertness as marker rhythms. PATIENTS: Six normal volunteers aged 22-26 years (mean +/- SD 24.3 +/- 1.4). DESIGN: Subjects were exposed to the following periods of moderately bright light (1200 lux) on three consecutive days in early December 1991: Day (D)1: 2000-0200 h, D2: 2200-0400 h and D3: 2400-0600 h. Each period was followed by 8 hours of darkness (< 1 lux). Hourly blood, sequential 4-hourly urine (8-hourly when asleep) and hourly saliva (except when asleep) samples were taken throughout a 24-hour period on D0 (baseline), D4 (1 day post-light treatment) and D7 (4 days post-light treatment). During waking hours, subjective alertness was rated every 2 hours on a visual analogue scale. MEASUREMENTS: MT was measured in plasma and saliva, and its metabolite, 6-sulphatoxymelatonin (aMT6s), was measured in urine. MT, aMT6s and alertness scores were analysed by ANOVA and a cosinor analysis program. RESULTS: A delay shift was present in the aMT6s, plasma MT and salivary MT rhythms (degree of shift: 2.67 +/- 0.3 h (P < 0.001, n = 5); 2.35 +/- 0.29 h (P < 0.001, n = 6); and 1.97 +/- 0.32 h (P < 0.01, n = 6), mean +/- SEM, respectively) 1 day post-light treatment compared to baseline. Adaptation to the initial phase position was apparent by the 4th post-treatment day. Significant correlations were obtained between plasma MT onset (degree of shift: 3.12 +/- 0.74 h (P < 0.001, n = 6, mean +/- SEM)) and the acrophases (calculated peak times) of plasma MT (P < 0.001), salivary MT (P < 0.05) and urinary aMT6s (P < 0.01). A significant phase delay in the alertness rhythm was also evident 1 day post-treatment (3.08 +/- 0.67 h (P < 0.01, n = 6, mean +/- SEM)) with adaptation by the 2nd post-treatment day. CONCLUSIONS: This study suggests that these methods of determining MT secretion are comparable and give reliable assessments of the MT circadian phase position even after a phase-shift. Significant phase-shifts of similar magnitude can be induced in both MT and alertness rhythms using moderate intensity bright light at night.     

Bright light affects alertness and performance rhythms during a 24-h constant routine

The aim of the present study was to assess the stimulating effects of bright light (BL) on subjective and objective alertness. Eight subjects were exposed to either bright light or dim light (DL) during a 24-h constant routine (0900-0900). Bright light failed to modify either the 24-h course or the level of body temperature. Compared to DL, BL delayed the circadian trough of motor activity by 2 h. During the night, relative to the dim-light condition, BL significantly increased subjective and objective (EEG test) alertness and improved performances. Thus, BL exposure partly counteracted the effects of sleep deprivation and/or the circadian trough on alertness and performances. During the day, BL only improved the mood and motivation levels. However, the time course of mood and motivation was not affected by the BL exposure, a nocturnal circadian trough occurring at 0630 in both light conditions.     

Phase shift magnitude and direction determine whether Siberian hamsters reentrain to the photocycle

Body temperature (Tb) or activity rhythms were monitored in male Siberian hamsters (Phodopus sungorus) housed in an LD cycle of 16 h light/day from birth. At 3 months of age, rhythms were monitored for 14 days, and then the LD cycle was phase delayed by 1, 3, or 5 h or phase advanced by 5 h in four separate groups of animals. Phase delays were accomplished via a 1- or 3-h extension of the light phase or via a 5-h extension of the dark phase. The phase advance was accomplished via a 5-h shortening of the light phase. After 2 to 3 weeks, hamsters that were phase delayed by 1 or 3 h were then phase advanced by 1 or 3 h, respectively, via a shortening of the light phase. All of the animals reentrained to phase delays of 1 or 3 h and to a 1-h phase advance; 79% reentrained to a 3-h phase advance. In contrast, only 13% of the animals reentrained to the 5-h phase advance, 13% became arrhythmic, and 74% free ran for several weeks. After the 5-h phase delay, however, reentrainment was observed in 50% of the animals although half of them required more than 21 days to reentrain. The response to a phase shift could not be predicted by any parameter of circadian rhythm organization assessed prior to the phase shift. These data demonstrate that a phase shift of the LD cycle can permanently disrupt entrainment mechanisms and eliminate circadian Tb and activity rhythms. Magnitude and direction of a phase shift of the LD cycle determine not only the rate but also the probability of reentrainment. Furthermore, the phase of the LD cycle at which the phase shift is made has a marked effect on the proportion of animals that reentrain. Light exposure during mid-subjective night combined with daily light exposure during the active phase may explain these phenomena.     

The therapeutic focus in significant sessions of master therapists: a comparison of cognitive-behavioral and psychodynamic-interpersonal interventions

This study was designed to test the hypothesis that bright light (BL) can have a stimulating effect on vigilance even in the absence of suppression of melatonin secretion and that this effect can be detected when measured in subjects with low vigilance levels. Seven normal subjects were exposed to bright-white light (BL group) and seven to dim-red light (DL group) on 2 consecutive days, each following a night of 4-h sleep restriction. The light treatment was administered in the late morning, between 0900 and 1330 hours. Salivary melatonin measurements indicated that BL did not suppress melatonin secretion or induce circadian phase shifts. The effects of the two treatments were compared on validated measures of daytime vigilance: immediate effects were evaluated on subjective alertness during the light treatment, whereas short-term (0.5-10.5 h) and long-term (20.5-34.5 h) carryover effects were measured on subjective alertness, daytime sleep latencies (DSL), and psychomotor performance. After two nights of sleep restriction, subjective alertness and daytime sleep latencies decreased significantly, but there was no effect of the light treatment. BL treatment did not affect global performance, but there was an effect on the strategy used by the subjects, as shown by faster reaction times and increased percentage of errors in the BL group. It was concluded that daytime BL exposure did not have a stimulating effect on our measures of vigilance even in sleep-deprived subjects but that it may increase physiological arousal and affect the subjects' behavior in some specific performance tasks.     

Circadian rhythms during gradually delaying and advancing sleep and light schedules

The circadian rhythms of the night shift worker show very little phase shift in response to the daytime sleep and night work schedule. One strategy for producing circadian adaptation may be to use appropriately timed exposure to high-intensity light. We attempted to shift the circadian temperature rhythms of seven normal subjects while they followed a sleep schedule that gradually delayed (2 h per day) until sleep occurred during the daytime, as is customary for workers during the night shift. After 5 days, the sleep schedule was gradually advanced back to baseline. High illuminance light (2 h per day) and the attenuation or avoidance of sunlight were timed to facilitate temperature rhythm phase shifts. In general, the temperature rhythm did not shift along with the sleep-wake schedule, but appeared either to free run or remain entrained to the natural 24-h zeitgebers. This study showed how difficult it can be to shift human circadian rhythms in the field, when subjects are exposed to competing 24-hr zeitgebers.     

Cortisol secretion is related to electroencephalographic alertness in human subjects during daytime wakefulness

To determine whether human hypothalamo-pituitary-adrenal axis activity is related to the alertness level during wakefulness, 10 healthy young men were studied under resting conditions in the daytime (0900-1800 h) after an 8-h nighttime sleep (2300-0700 h). A serial 70-sec gaze fixation task was required every 10 min throughout the daytime experimental session. The corresponding waking electroencephalographic (EEG) segments were submitted to quantitative spectral analysis, from which EEG beta activity (absolute power density in the 13-35 Hz frequency band), an index of central alertness, was computed. Blood was collected continuously through an indwelling venous catheter and sampled at 10-min intervals. Plasma cortisol concentrations were measured by RIA, and the corresponding secretory rates were determined by a deconvolution procedure. Analysis of individual profiles demonstrated a declining tendency for EEG beta activity and cortisol secretory rate, with an overall temporal relationship indicated by positive and significant cross-correlation coefficients between the two variables in all subjects (average r=0.565, P < 0.001). Changes in cortisol secretion lagged behind fluctuations in EEG beta activity, with an average delay of 10 min for all the subjects. On the average, 4.6+/-0.4 cortisol secretory pulses and 4.9+/-0.5 peaks in EEG beta activity were identified by a detection algorithm. A significant, although not systematic, association between the episodes in the two variables was found: 44% of the peaks in EEG beta activity (relative amplitude, near 125%; P < 0.001) occurred during an ascending phase of cortisol secretion, cortisol secretory rates increasing by 40% (P < 0.01) 10-min after peaks in EEG beta activity. However, no significant change in EEG beta activity was observed during the period from 50 min before to 50 min after pulses in cortisol secretion. In conclusion, the present study describes a temporal coupling between cortisol release and central alertness, as reflected in the waking EEG beta activity. These findings suggest the existence of connections between the mechanisms involved in the control of hypothalamo-pituitary-adrenal activity and the activation processes of the brain, which undergoes varying degrees of alertness throughout daytime wakefulness.     

Morning vs evening light treatment of patients with winter depression

BACKGROUND: According to the phase-shift hypothesis for winter depression, morning light (which causes a circadian phase advance) should be more antidepressant than evening light (which causes a delay). Although no studies have shown evening light to be more antidepressant than morning light, investigations have shown either no difference or morning light to be superior. The present study assesses these light-exposure schedules in both crossover and parallel-group comparisons. METHODS: Fifty-one patients and 49 matched controls were studied for 6 weeks. After a prebaseline assessment and a light/dark and sleep/wake adaptation baseline week, subjects were exposed to bright light at either 6 to 8 AM or 7 to 9 PM for 2 weeks. After a week of withdrawal from light treatment, they were crossed over to the other light schedule. Dim-light melatonin onsets were obtained 7 times during the study to assess circadian phase position. RESULTS: Morning light phase-advanced the dim-light melatonin onset and was more antidepressant than evening light, which phase-delayed it. These findings were statistically significant for both crossover and parallel-group comparisons. Dim-light melatonin onsets were generally delayed in the patients compared with the controls. CONCLUSIONS: These results should help establish the importance of circadian (morning or evening) time of light exposure in the treatment of winter depression. We recommend that bright-light exposure be scheduled immediately on awakening in the treatment of most patients with seasonal affective disorder.     

Temporal correlation between neuronal tail ganglion activity and locomotion in the leech, Hirudo medicinalis

A field study of work and sleep patterns among commercial merchant marine personnel is reported. Data collected over a 10-30-d period from 141 subjects aboard eight ships included information concerning work-rest schedules, sleep timing, alertness on the job and critical fatigue. The data indicate that watchstanders on the 4-on, 8-off schedule show considerable disruption in their sleep. The average sleep duration for all mariners is 6.6 h; watchstanders obtain their sleep in fragmented periods that are frequently less than 5 h in duration. Analysis of critical fatigue shows an incidence of 1-24% across personnel and measures. Of particular concern are the watchstanders on the 04.00-08.00 schedule, who sleep less than 4 h per 24-h period 22% of the time. Potential countermeasures, including changes in scheduling and staffing are proposed.     

Acute effects of recombinant human interleukin-6 on endocrine and central nervous sleep functions in healthy men

Interleukin-6 (IL-6) is a proinflammatory cytokine that has been shown to mediate, in addition to immune reactions, various endocrine and central nervous components of the acute phase response. In this context, the present study aimed to specify the contributions of IL-6 to the regulation of pituitary-adrenal secretory activity and GH and TSH secretion, as well as to the regulation of central nervous sleep and mood in healthy men. Effects of a low dose of IL-6 (0.5 microgram/kg body weight) were assessed, inducing plasma IL-6 concentrations closely comparable with those typically observed after infectious challenge. Each of the 16 male subjects participated in two 14-h sessions (between 1800 and 0800 h), receiving either placebo or human recombinant IL-6 sc at 1900 h. Blood was collected repeatedly to determine plasma hormone levels, serum concentrations of cytokines, and C-reactive protein. Moreover, mood was assessed, and sleep recordings were obtained between 2300 and 0700 h. The cytokine induced a prolonged increased in plasma concentrations of ACTH and cortisol (P < 0.001), but led to a decrease in TSH concentrations (P < 0.01). In response to IL-6, subjects reported fatigue and felt more inactive and less capable of concentrating than after placebo. Sleep architecture was altered significantly by the cytokine. Slow-wave sleep was decreased during the first half and increased during the second half of sleep. Rapid eye movement sleep during the entire nocturnal sleep time was significantly decreased. After IL-6, body temperature rose slightly. C-reactive protein concentrations were dramatically increased 12.5 h after substance administration (P < 0.001). IL-6 did not affect serum concentrations of IL-2, IL-8, interferon-alpha, and interferon-gamma. The results underscore the importance of IL-6 in the cascade of cytokines for the neuroendocrine response during the acute phase reaction. In addition, IL-6 appears to be involved in changes of sleep and behavior accompanying infection and inflammatory disorders.     

Sleep and circadian rhythms in four orbiting astronauts

This experiment measured the sleep and circadian rhythms of four male astronauts aboard a space shuttle (STS-78) orbiting the Earth for 17 days. The space mission was specially scheduled to minimize disruptions in circadian rhythms and sleep so that the effects of space flight and microgravity per se could be studied. Data were collected in 72-h measurement blocks: one block 7 days before launch, one early within the mission (3 days after launch), one late in the mission (12 days after launch), and one 18 days after landing. Within each measurement block, all sleep was recorded both polysomnographically and by sleep diary. Core body temperature was sampled every 6 mins. Actillumes were worn continuously. All urine samples were collected separately. Performance was assessed by a computerized test battery (3/day) and by end-of-shift questionnaires (1/day); mood and alertness were measured by visual analogue scales (5/day). Circadian rhythms in orbit appeared to be very similar in phase and amplitude to those on the ground, and were appropriately aligned for the required work/rest schedule. There was no change from early flight to late flight. This was also reflected in mood, alertness, and performance scores, which were satisfactory at both in-flight time points. However, in-flight sleep showed a decreased amount of sleep obtained (mean = 6.1 h), and all four astronauts showed a decrease in delta sleep. No further degradation in sleep was seen when early flight was compared to late flight, and no other sleep parameters showed reliable trends.     

Tripartite hemolysin BL from Bacillus cereus. Hemolytic analysis of component interactions and a model for its characteristic paradoxical zone phenomenon

This study describes the use of the microdialysis technique to elucidate specific properties of the circadian pacemaking system in the hypothalamus, by measurement of melatonin production in the pineal gland. Melatonin has appeared to be a reliable marker of the pacemaker activity, which is influenced by the light/dark cycle. A phase shift in the light/dark cycle was applied to perturb the rhythm generating system. An 8-h phase advance resulted in the disappearance of melatonin production over two days, with basal levels comparable to normal daytime levels. In the subsequent return of rhythmic melatonin production, new clock characteristics could be revealed, due to the high time-resolution measurements of microdialysis. While half of the animals still did not show any rhythmicity, the other half of the animals regained rhythmicity with entrained onset of melatonin production, while the offset was variable and not stably entrained to lights on. Ten days after the shift, the system had completely recovered and all animals regained normal rhythmicity, in phase with the new light/dark cycle. The results are interpreted in terms of the two-oscillator model, with one oscillator reacting with a phase advance and the other with a phase delay to adapt to the phase shift.     

Acquired segmental iris dilator muscle synkinesis due to deglutition

Six healthy male subjects aged 21-35 years participated in the present study. The subjects were exposed to dim light (150 lux) or bright light (3000 lux) at eye level, from 19.00 to 21.30 h for 5 days. Rectal temperature and wrist activity were monitored throughout the study period. Rectal temperature nadir was delayed significantly after the bright light exposure. Ease in sleep initiation and overall sleep quality, measured by questionnaire, were aggravated significantly by the evening bright light exposure. These results suggest that strong illumination at night may disturb nocturnal sleep.     

Imaging of pediatric head and neck rhabdomyosarcomas with emphasis on magnetic resonance imaging and a review of the literature

In the mouse, the initiation of the attachment reaction between the blastocyst trophectoderm and luminal epithelium of the receptive uterus occurs in the evening (2200-2300 h) of day 4 of pregnancy (day 1 = vaginal plug) and is followed by proliferation and differentiation of stromal cells into decidual cells at the sites of blastocyst attachment. This investigation demonstrates that an inappropriate expression of the human transforming growth factor alpha (hTGF-alpha) transgene in the uterus under the direction of a mouse metallothionein-I promoter downregulates uterine expression of TGF-beta receptor subtypes and delays the initiation of implantation (attachment reaction) resulting in delayed parturition. This delay in the attachment reaction is accompanied by deferred uterine expression of amphiregulin. The results suggest that a coordinated 'cross-talk' between the signaling pathways executed by epidermal growth factor-like growth factors and TGF-beta 5 is important for the normal implantation process.     

Melatonin treatment for circadian rhythm sleep disorders

We administered 1-3 mg melatonin to 11 patients (eight men, three women, aged 16-46 years) with circadian rhythm sleep disorders; nine with delayed sleep phase syndrome and two with non-24-hour sleep-wake syndrome. Sleep logs were recorded throughout the study periods and actigraph and rectal temperature were monitored during treatment periods. Melatonin was administered 1-2 h before the desirable bedtime for expected phase-shifting, or 0.5-1 h before habitual bedtime for gradual advance expecting an hypnotic effect of the melatonin. Melatonin treatments were successful in 6/11 patients. Timing and dose of melatonin administration, together with its pharmacological properties for circadian rhythm sleep disorders, should be further studied.     

Melatonin and delayed sleep phase syndrome: ambulatory polygraphic evaluation

The present study objectively evaluated the efficacy of oral 5 mg day-1 melatonin in advancing the sleep-wake rhythm in patients with delayed sleep phase syndrome (DSPS). Six patients underwent ambulatory sleep monitoring for 72 h before and 48 h after 1 month of melatonin treatment. In each patient melatonin was administered on the basis of his own estimated dim light melatonin onset (DLMO) delay. Mean advances in sleep onset time of 115 min and in final awakening hour of 106 min were found after treatment, with no significant changes in sleep architecture parameters. Our study objectively confirms previous data obtained by a sleep-wake subjective diary on the efficacy of melatonin DSPS.     

Broad, but not universal, transcriptional requirement for yTAFII17, a histone H3-like TAFII present in TFIID and SAGA

1. In 2 experiments with Single Comb White Leghorn hens, the effects of different light:dark cycles (LD-cycles) upon oviposition patterns and plasma melatonin rhythms were studied. In experiment 1, a 28-h ahemeral LD-cycle (12L:16D) was used. In experiment 2, a normal 24-h LD-cycle (16L:8D) was applied and the effects of a sudden 8-h forward or backward shift of the 8-h dark period (that is phase-advanced or phase-delayed LD-cycle) were studied. 2. The oviposition patterns as well as the plasma melatonin rhythms were fully synchronised with both LD-cycles (24-h or 28-h). The 2 rhythms were gradually re-synchronised after phase shifts, and the melatonin response phase-led the oviposition response by 2 cycles. Thus, the change of the melatonin rhythm coincided with the change of the (presumed) open period for LH-release. 3. In the unchanged 24-h LD-cycle, ovipositions occurred almost exclusively (98.9%) during light hours, whereas in the 28-h LD-cycle, ovipositions occurred primarily (84.5%) during the last 9 h of the dark period. 4. In both LD-cycles and after changes of the LD-cycle, light always suppressed plasma melatonin, regardless of previous light history. During dark periods, concentrations were elevated but, interestingly, only if darkness had also been experienced during the same time period 24 h earlier. This indicates that light has a direct inhibiting effect upon pineal melatonin release, while actual melatonin release during darkness is controlled by an endogenous clock.     

Selective MT2 melatonin receptor antagonists block melatonin-mediated phase advances of circadian rhythms

This study demonstrates the involvement of the MT2 (Mel1b) melatonin receptor in mediating phase advances of circadian activity rhythms by melatonin. In situ hybridization histochemistry with digoxigenin-labeled oligonucleotide probes revealed for the first time the expression of mt1 and MT2 melatonin receptor mRNA within the suprachiasmatic nucleus of the C3H/HeN mouse. Melatonin (0.9 to 30 microg/mouse, s.c.) administration during 3 days at the end of the subjective day (CT 10) to C3H/HeN mice kept in constant dark phase advanced circadian rhythms of wheel running activity in a dose-dependent manner [EC50=0.72 microg/mouse; 0.98+/-0.08 h (n=15) maximal advance at 9 microg/mouse]. Neither the selective MT2 melatonin receptor antagonists 4P-ADOT and 4P-PDOT (90 microg/mouse, s.c.) nor luzindole (300 microg/mouse, s.c.), which shows 25-fold higher affinity for the MT2 than the mt1 subtype, affected the phase of circadian activity rhythms when given alone at CT 10. All three antagonists, however, shifted to the right the dose-response curve to melatonin, as they significantly reduced the phase shifting effects of 0.9 and 3 microg melatonin. This is the first study to demonstrate that melatonin phase advances circadian rhythms by activation of a membrane-bound melatonin receptor and strongly suggests that this effect is mediated through the MT2 melatonin receptor subtype within the circadian timing system. We conclude that the MT2 melatonin receptor subtype is a novel therapeutic target for the development of subtype-selective analogs for the treatment of circadian sleep and mood-related disorders.     

Performance deficits following short-term partial sleep deprivation and subsequent recovery oversleeping.

Tested the effects on performance of 1 and 5 cumulative nights of partial sleep deprivation (PSD; less than 40% per night) and 1 and 2 nights of subsequent recovery oversleep (+40%, +20% respectively), compared to pre- and postbaselines in 7 undergraduates (18–23 yrs). Assessment measures included the standard 1-hr Wilkinson auditory vigilance test, 2 RT tests, the Stanford Sleepiness Scale, and Ss' self-ratings. The experiment lasted 8 days, and Ss were tested twice each day for 2 hrs. Results show deficits in performance on the vigilance and RT tests, as well as lower self-ratings of alertness and energy and other transient deficits after 5 nights PSD. Time of day effects were most pronounced on the initial days following sleep reduction or gain. Results indicate that a typical work week of undersleeping on weekdays and oversleeping on weekends may produce performance deficits. This may be due to a sudden shift in the phase of sleep, rather than sleep loss per se. (French abstract) (48 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)