Enhanced conductive body heat loss during sleep increases slow-wave sleep and calms the heart.

Substantial evidence suggests that the circadian decline of core body temperature (CBT) triggers the initiation of human sleep, with CBT continuing to decrease during sleep. Although the connection between habitual sleep and CBT patterns is established, the impact of external body cooling on sleep remains poorly understood. The main aim of the present study is to show whether a decline in body temperatures during sleep can be related to an increase in slow wave sleep (N3). This three-center study on 72 individuals of varying age, sex, and BMI used an identical type of a high-heat capacity mattress as a reproducible, non-disturbing way of body cooling, accompanied by measurements of CBT and proximal back skin temperatures, heart rate and sleep (polysomnography). The main findings were an increase in nocturnal sleep stage N3 (7.5 ± 21.6 min/7.5 h, mean ± SD; p = 0.0038) and a decrease in heart rate (- 2.36 ± 1.08 bpm, mean ± SD; p < 0.0001); sleep stage REM did not change (p = 0.3564). Subjects with a greater degree of body cooling exhibited a significant increase in nocturnal N3 and a decrease in REM sleep, mainly in the second part of the night. In addition, these subjects showed a phase advance in the NREM-REM sleep cycle distribution of N3 and REM. Both effects were significantly associated with increased conductive inner heat transfer, indicated by an increased CBT- proximal back skin temperature -gradient, rather than with changes in CBT itself. Our findings reveal a previously far disregarded mechanism in sleep research that has potential therapeutic implications: Conductive body cooling during sleep is a reliable method for promoting N3 and reducing heart rate.

Effects of manipulating body temperature on sleep in postmenopausal women.

STUDY OBJECTIVES: A decline in sleep quality, slow wave sleep (SWS) and slow wave activity (SWA) are common in older adults. Prior studies have shown that manipulating body temperature during sleep can increase SWS/SWA. The aim of this study was to determine the effects of manipulation of body temperatures during sleep, using a high heat capacity mattress, on SWS/SWA and heart rate in post-menopausal women. METHODS: Twenty-four healthy postmenopausal women between 40 and 75 years of age (mean age 62.4 ± 8.2 years, mean BMI 25.4 ± 3.5 kg/m2) were randomized in a single-blind, counterbalanced, cross-over manner to sleep on either a high heat capacity mattress (HHCM) or a low heat capacity mattress (LHCM) a week apart. Sleep was recorded using polysomnography during an 8-h sleep opportunity. Core and peripheral temperature were recorded using an ingestible capsule and thermochron respectively. RESULTS: In comparison to the LHCM, sleep on HHCM exhibited a selective increase in SWS (average increase in Stage N3 of 9.6 min (2.1%), p = 0.04) and in slow oscillatory (SO) activity (0.5-1 Hz) in the first NREM/REM cycle (p = 0.04). In addition, the HHCM induced a greater reduction in core body temperature (p = 0.002). The reduction in core body temperature (first 180 min after lights out) from LHCM to HHCM was associated (r = 0.5, p = 0.012) with the increase in SO activity (SO cycle 1 and 2/cycle 3 and 4). Average heart rate was 1.6 beats/minute lower across the night on the HHCM compared to the LHCM (p = 0.001). CONCLUSIONS: The results of this study indicate that manipulation of body temperature during sleep may be a useful approach to enhance SWS sleep in postmenopausal women.

Effects of sleep on a high-heat capacity mattress on sleep stages, EEG power spectra, cardiac interbeat intervals and body temperatures in healthy middle-aged men‡.

STUDY OBJECTIVES: This study deals with the question whether a slow (non-disturbing) reduction of core body temperature (CBT) during sleep increases sleep stage N3 and EEG slow wave energy (SWE) and leads to a slowing of heart rate in humans. PARTICIPANTS: Thirty-two healthy male subjects with a mean ± SD age 46 ± 4 years and body mass index 25.2 ± 1.8 kg/m2. METHODS: A high-heat capacity mattress (HM) was used to lower body temperatures in sleep and was compared to a conventional low-heat capacity mattress (LM) in a double-blinded fashion. Polysomnography was performed accompanied by measurements of skin-, core body- and mattress surface-temperatures, and heart rate. EEG power spectral analyses were carried out using Fast Fourier Transform. Interbeat intervals were derived from the electrocardiogram. RESULTS: The HM led to a larger decline in CBT, mediated through higher heat conduction from the core via the proximal back skin onto the mattress together with reduced heart rate. These effects occurred together with a significant increase in sleep stage N3 and standardized slow wave energy (sSWE, 0.791-4.297 Hz) accumulated in NREM sleep. In the 2nd half of the night sSWE increase was significantly correlated with body temperature changes, for example with CBT decline in the same phase. CONCLUSIONS: A HM subtly decreases CBT, leading to an increased amount of sleep stage N3 and of sSWE, as well as a slowing of heart rate.

Sleep on a high heat capacity mattress increases conductive body heat loss and slow wave sleep.

Environmental temperature can strongly affect sleep. The habitual sleep phase is usually located between evening decline and morning rise of the circadian rhythm of core body temperature (CBT). However, the thermophysiological mechanisms promoting or disturbing sleep are not yet fully understood. The purpose of this study was to examine the effects of a high heat capacity mattress (HHCM) on CBT, skin temperatures and sleep in comparison to a conventional low heat capacity mattress (LHCM). Based on the higher heat capacity of HHCM an increase in conductive body heat loss enhances the nocturnal decline in CBT can be expected. Based on previous findings this may then be accompanied by an increase in slow wave sleep (SWS). The mattresses were studied in a randomized single-blind crossover design in fifteen healthy young men (Age: 26.9±2.1yr, BMI: 22.2±0.4kg/m2) by overnight in laboratory standard video-polysomnography in a temperature stabilized setting. CBT, room temperature, and skin and mattress surface temperatures were continuously recorded in order to get information about inner and outer body heat flow. Additionally, subjective sleep quality was estimated by visual analogue scale. In comparison to LHCM sleep on HHCM exhibited a selective increase in SWS (16%, p<0.05), increased subjective sleep quality and sleep stability [reduced cyclic alternating pattern (CAP) rate; 5.3%, p<0.01]. Additionally, analyses of the sleep stages showed in the second part of the night a significant increase in SWS and a decrease in REMS. In addition, HHCM induced a greater reduction in CBT (maximally by -0.28°C), reduced the increase in proximal skin temperatures on the back (PROBA; maximally by -0.98°C), and delayed the increase in mattress surface temperature (maximal difference LHCM-HHCM: 6.12°C). Thus, the CBT reduction can be explained by an increase in conductive heat loss to the mattress via proximal back skin regions. Regression analysis identified PROBA as the critical variable to predict inner conductive heat transfer from core to shell and SWS. In conclusion, the study expands the previous findings that a steeper nocturnal decline in CBT increases SWS and subjective sleep quality, whereas inner conductive heat transfer could be identified as the crucial thermophysiological variable, and not CBT.

Daytime variation in ambient temperature affects skin temperatures and blood pressure: Ambulatory winter/summer comparison in healthy young women.

It is widely accepted that cold exposure increases peripheral vascular resistance and arterial blood pressure (BP) and, hence, increases cardiovascular risk primarily in the elderly. However, there is a lack of concomitantly longitudinal recordings at personal level of environmental temperature (PET) and cardiophysiological variables together with skin temperatures (STs, the "interface-variable" between the body core and ambient temperature). To investigate the intra-individual temporal relationships between PET, STs and BP 60 healthy young women (52 completed the entire study) were prospectively studied in a winter/summer design for 26 h under real life conditions. The main hypothesis was tested whether distal ST (Tdist)mediates the effect of PET-changes on mean arterial BP (MAP). Diurnal profiles of cardiophysiological variables (including BP), STs and PET were ambulatory recorded. Daytime variations between 0930 and 2030 h were analyzed in detail by intra-individual longitudinal path analysis. Additionally, time segments before, during and after outdoor exposure were separately analyzed. In both seasons short-term variations in PET were positively associated with short-term changes in Tdist (not proximal ST, Tprox) and negatively with those in MAP. However, long-term seasonal differences in daytime mean levels were observed in STs but not in BP leading to non-significant inter-individual correlation between STs and BP. Additionally, higher individual body mass index (BMI) was significantly associated with lower daytime mean levels of Tprox and higher MAP suggesting Tprox as potential mediator variable for the association of BMI with MAP. In healthy young women the thermoregulatory and BP-regulatory systems are closely linked with respect to short-term, but not long-term changes in PET. One hypothetical explanation could serve recent findings that thermogenesis in brown adipose tissue is activated in a cool environment, which could be responsible for the counter-regulation of cold induced increase of BP in winter leading to no seasonal differences in MAP. Our findings suggest that the assessment of diurnal patterns of STs and PET, in addition to the conventional ambulatory BP monitoring, might improve individual cardiovascular risk prediction.

Diurnal and menstrual cycles in body temperature are regulated differently: a 28-day ambulatory study in healthy women with thermal discomfort of cold extremities and controls.

Diurnal cycle variations in body-heat loss and heat production, and their resulting core body temperature (CBT), are relatively well investigated; however, little is known about their variations across the menstrual cycle under ambulatory conditions. The main purpose of this study was to determine whether menstrual cycle variations in distal and proximal skin temperatures exhibit similar patterns to those of diurnal variations, with lower internal heat conductance when CBT is high, i.e. during the luteal phase. Furthermore, we tested these relationships in two groups of women, with and without thermal discomfort of cold extremities (TDCE). In total, 19 healthy eumenorrheic women with regular menstrual cycles (28-32 days), 9 with habitual TDCE (ages 29 ± 1.5 year; BMI 20.1 ± 0.4) and 10 controls without these symptoms (CON: aged 27 ± 0.8 year; BMI 22.7 ± 0.6; p < 0.004 different to TDCE) took part in the study. Twenty-eight days continuous ambulatory skin temperature measurements of distal (mean of hands and feet) and proximal (mean of sternum and infraclavicular regions) skin regions, thighs, and calves were carried out under real-life, ambulatory conditions (i-Buttons® skin probes, sampling rate: 2.5 min). The distal minus proximal skin temperature gradient (DPG) provided a valuable measure for heat redistribution from the core to the shell, and, hence, for internal heat conduction. Additionally, basal body temperature was measured sublingually directly after waking up in bed. Mean diurnal amplitudes in skin temperatures increased from proximal to distal skin regions and the 24-h mean values were inversely related. TDCE compared to CON showed significantly lower hand skin temperatures and DPG during daytime. However, menstrual cycle phase did not modify these diurnal patterns, indicating that menstrual and diurnal cycle variations in skin temperatures reveal additive effects. Most striking was the finding that all measured skin temperatures, together with basal body temperature, revealed a similar menstrual cycle variation (independent of BMI), with highest and lowest values during the luteal and follicular phases, respectively. These findings lead to the conclusion that in contrast to diurnal cycle, variations in CBT variation across the menstrual cycle cannot be explained by changes in internal heat conduction under ambulatory conditions. Although no measurements of metabolic heat production were carried out increased metabolic heat generation during the luteal phase seems to be the most plausible explanation for similar body temperature increases.

Diurnal blood pressure variations are associated with changes in distal-proximal skin temperature gradient.

It is generally assumed that skin vascular resistance contributes only to a small extent to total peripheral resistance and hence to blood pressure (BP). However, little is known about the impact of skin blood flow (SBF) changes on the diurnal variations of BP under ambulatory conditions. The main aim of the study was to determine whether diurnal patterns of distal SBF are related to mean arterial BP (MAP). Twenty-four-hour ambulatory measurements of BP, heart rate (HR) and distal (mean of hands and feet) as well as proximal (mean of sternum and infraclavicular region) skin temperatures were carried out in 51 patients (men/women = 18/33) during a 2-d eye hospital investigation. The standardized ambulatory protocol allowed measurements with minimal interference from uncontrolled parameters and, hence, some conclusive interpretations. The distal minus proximal skin temperature gradient (DPG) provided a measure for distal SBF. Individual cross-correlation analyses revealed that the diurnal pattern of MAP was nearly a mirror image of DPG and hence of distal SBF. Scheduled lunch and dinner induced an increase in DPG and a decline in MAP, while HR increased. Low daytime DPG (i.e. low distal SBF) levels significantly predicted sleep-induced BP dipping (r = -.436, p = .0014). Preliminary path analysis suggested that outdoor air temperature and atmospheric pressure may act on MAP via changed distal SBF. Changes in distal SBF may contribute to diurnal variation in MAP, including sleep-induced BP dipping and changes related to food intake. This finding might have an impact on individual cardiovascular risk prediction with respect to diurnal, seasonal and weather variations; however, the underlying mechanisms remain to be discovered.

An improved method for estimating human circadian phase derived from multichannel ambulatory monitoring and artificial neural networks.

Recently, we developed a novel method for estimating human circadian phase with noninvasive ambulatory measurements combined with subject-independent multiple regression models and a curve-fitting approach. With this, we were able to estimate circadian phase under real-life conditions with low subject burden, i.e., without need of constant routine (CR) laboratory conditions, and without measuring standard circadian markers, such as core body temperature (CBT) or pineal hormone melatonin rhythms. The precision of ambulatory-derived estimated circadian phase was within an error of 12 ± 41 min (mean ± SD) in comparison to melatonin phase during a CR protocol. The physiological measures could be reduced to a triple combination: skin temperatures, irradiance in the blue spectral band of ambient light, and motion acceleration. Here, we present a nonlinear regression model approach based on artificial neural networks for a larger data set (25 healthy young males), including both the original data and additional data collected in the same protocol and using the same equipment. Throughout our validation study, subjects wore multichannel ambulatory monitoring devices and went about their daily routine for 1 wk. The devices collected a large number of physiological, behavioral, and environmental variables, including CBT, skin temperatures, cardiovascular and respiratory functions, movement/posture, ambient temperature, spectral composition and intensity of light perceived at eye level, and sleep logs. After the ambulatory phase, study volunteers underwent a 32-h CR protocol in the laboratory for measuring unmasked circadian phase (i.e., "midpoint" of the nighttime melatonin rhythm). To overcome the complex masking effects of many different confounding variables during ambulatory measurements, neural network-based nonlinear regression techniques were applied in combination with the cross-validation approach to subject-independent prediction of circadian phase. The most accurate estimate of circadian phase with a prediction error of -3 ± 23 min (mean ± SD) was achieved using only two types of the measured variables: skin temperatures and irradiance for ambient light in the blue spectral band. Compared to our previous linear multiple regression modeling approach, motion acceleration data can be excluded and prediction accuracy, nevertheless, improved. Neural network regression showed statistically significant improvement of variance of prediction error over traditional approaches in determining circadian phase based on single predictors (CBT, motion acceleration, or sleep logs), even though none of these variables was included as predictor. We, therefore, have identified two sets of noninvasive measures that, combined with the prediction model, can provide researchers and clinicians with a precise measure of internal time, in spite of the masking effects of daily behavior. This method, here validated in healthy young men, requires testing in a clinical or shiftwork population suffering from circadian sleep-wake disorders.

Estimation of human circadian phase via a multi-channel ambulatory monitoring system and a multiple regression model.

Reliable detection of circadian phase in humans using noninvasive ambulatory measurements in real-life conditions is challenging and still an unsolved problem. The masking effects of everyday behavior and environmental input such as physical activity and light on the measured variables need to be considered critically. Here, we aimed at developing techniques for estimating circadian phase with the lowest subject burden possible, that is, without the need of constant routine (CR) laboratory conditions or without measuring the standard circadian markers, (rectal) core body temperature (CBT), and melatonin levels. In this validation study, subjects (N = 16) wore multi-channel ambulatory monitoring devices and went about their daily routine for 1 week. The devices measured a large number of physiological, behavioral, and environmental variables, including CBT, skin temperatures, cardiovascular and respiratory function, movement/posture, ambient temperature, and the spectral composition and intensity of light received at eye level. Sleep diaries were logged electronically. After the ambulatory phase, subjects underwent a 32-h CR procedure in the laboratory for measuring unmasked circadian phase based on the "midpoint" of the salivary melatonin profile. To overcome the complex masking effects of confounding variables during ambulatory measurements, multiple regression techniques were applied in combination with the cross-validation approach to subject-independent prediction of circadian phase. The most accurate estimate of circadian phase was achieved using skin temperatures, irradiance for ambient light in the blue spectral band, and motion acceleration as predictors with lags of up to 24 h. Multiple regression showed statistically significant improvement of variance of prediction error over the traditional approaches to determining circadian phase based on single predictors (motion acceleration or sleep log), although CBT was intentionally not included as the predictor. Compared to CBT alone, our method resulted in a 40% smaller range of prediction errors and a nonsignificant reduction of error variance. The proposed noninvasive measurement method could find applications in sleep medicine or in other domains where knowing the exact endogenous circadian phase is important (e.g., for the timing of light therapy).

Phase relationship between skin temperature and sleep-wake rhythms in women with vascular dysregulation and controls under real-life conditions.

The aim of the study was to investigate whether women with primary vascular dysregulation (VD; main symptoms of thermal discomfort with cold extremities) and difficulties initiating sleep (DIS) exhibit a disturbed phase of entrainment (Ψ) under everyday life conditions. The authors predicted a phase delay of the distal-proximal skin temperature gradient and salivary melatonin rhythms with respect to the sleep-wake cycle in women with VD and DIS (WVD) compared to controls (CON), similar to that found in their previous constant-routine laboratory data. A total of 41 young healthy women, 20 with WVD and 21 matched CON without VD and normal sleep onset latency (SOL), were investigated under ambulatory conditions (following their habitual bedtimes) during 7 days of continuous recording of skin temperatures, sleep-wake cycles monitored by actimetry and sleep-wake diaries, and single evening saliva collections for determining the circadian marker of dim light melatonin onset (DLMO). Compared to CON, WVD showed increased distal vasoconstriction at midday and in the evening, as indicated by lower distal (DIST; hands and feet) and foot-calf skin temperatures, and distal-proximal skin temperature gradients (p< .05). WVD manifested distal vasoconstriction before lights-off that also lasted longer after lights-off than in CON. In parallel, WVD exhibited a longer SOL (p< .05). To define internal phase-relationships, cross-correlation analyses were performed using diurnal rhythms of wrist activity and foot skin temperature. WVD showed a phase delay in foot skin temperature (CON versus WVD: 3.57 ± 17.28 min versus 38.50 ± 16.65 min; p< .05) but not in wrist activity. This finding was validated by additional within-subject cross-correlation analyses using the diurnal wrist activity pattern as reference. DLMO and habitual sleep times did not differ between CON and WVD. The authors conclude that WVD exhibit a phase delay of distal vasodilatation with respect to their habitual sleep-wake cycle and other circadian phase markers, such as DLMO. A full factorial design will have to show whether the finding is specific to primary vascular dysregulation, to DIS, or to their interaction.

Heart-rate variability in women during 40-hour prolonged wakefulness.

Heart-rate variability patterns of 18 women during a 40-h constant routine of prolonged wakefulness under controlled laboratory conditions were analyzed. The authors tested the circadian timing of the autonomic nervous system and the relationship between the sympathetic and vagal branches in women with both a functional disorder of vascular regulation (main symptom: cold hands and feet) and prolonged sleep onset and controls without these symptoms. Spectral analysis of R-R intervals during paced breathing episodes revealed significantly lower power values in the high-frequency band (HF; 0.15-0.4 Hz) but not in the low-frequency band (LF; 0.04-0.15 Hz), leading to a significantly elevated LF/HF ratio in the former group. A significant circadian rhythm in LF power and heart rate occurred in both groups, and a significant correlation was found between sleepiness and sympathovagal balance (r = .53, p < .05). These findings indicate not only an autonomic imbalance in the first group compared with controls, but also two strategies of the autonomic nervous system to fight against fatigue in women. One implies circadian control and the other homeostatic control, and both are reflected by the LF/HF ratio.

Thermal discomfort with cold extremities in relation to age, gender, and body mass index in a random sample of a Swiss urban population.

BACKGROUND: The aim of this epidemiological study was to investigate the relationship of thermal discomfort with cold extremities (TDCE) to age, gender, and body mass index (BMI) in a Swiss urban population. METHODS: In a random population sample of Basel city, 2,800 subjects aged 20-40 years were asked to complete a questionnaire evaluating the extent of cold extremities. Values of cold extremities were based on questionnaire-derived scores. The correlation of age, gender, and BMI to TDCE was analyzed using multiple regression analysis. RESULTS: A total of 1,001 women (72.3% response rate) and 809 men (60% response rate) returned a completed questionnaire. Statistical analyses revealed the following findings: Younger subjects suffered more intensely from cold extremities than the elderly, and women suffered more than men (particularly younger women). Slimmer subjects suffered significantly more often from cold extremities than subjects with higher BMIs. CONCLUSIONS: Thermal discomfort with cold extremities (a relevant symptom of primary vascular dysregulation) occurs at highest intensity in younger, slimmer women and at lowest intensity in elderly, stouter men.

The interrelationship between sleep regulation and thermoregulation.

The circadian distribution of vigilance states and body temperature changes are tightly coupled. The increase in heat loss at the end of the day is associated with increased ease to fall asleep. Experimental data show that warming the skin or the brain can increase sleep propensity, sleep consolidation, and the duration of sleep. Anatomical and neurophysiological studies show that the pre-optic-anterior-hypothalamus (POAH) is the main integrator of sleep and thermoregulatory information. It integrates information on vigilance states, body temperature, and environmental temperature and influences vigilance states and body temperature in response. Animals that display daily torpor may be a valuable model to investigate the relationship between sleep and thermoregulation. During torpor these animals seem to apply similar strategies and physiological processes as humans during entrance into sleep, but in a more extreme way, providing an excellent opportunity to investigate these processes in more detail. More systematic investigations are needed to further our understanding of the relationship between sleep and thermoregulation, and may provide the basis to treat sleep disturbances with thermal strategies.

Relationship between gender role, anger expression, thermal discomfort and sleep onset latency in women.

BACKGROUND: Women with thermal discomfort from cold extremities (hands and feet; TDCE) often suffer from prolonged sleep onset latency (SOL). Suppressed anger could contribute to the genesis of both TDCE and prolonged SOL. The aim of the study was to test the hypothesis whether stereotypic feminine gender socialization (SFGS) is related to anger suppression (experienced anger inwards, Anger-In), which in turn could affect TDCE and SOL. METHODS: 148 women, a sub-sample of a larger survey carried out in the Canton Basel-Stadt (Switzerland), sent back detailed postal questionnaires about SOL, TDCE, anger expression (STAXI, state -trait -anger -expression -inventory) and SFGS using a gender power inventory, estimating the degree of gender specific power expression explicitly within women by stereotypic feminine or male attribution. Statistics was performed by path analysis. RESULTS: A significant direct path was found from stereotypic feminine attribution to Anger-In and prolonged SOL. Additionally, a further indirect path from Anger-In via TDCE to SOL was found. In contrast, stereotypic male attribution was not related to Anger-In but was significantly associated with outwardly expressed anger. LIMITATIONS: Self-reported data, retrospective cross-sectional survey, prospective studies are required including physiological measurements. CONCLUSION: Stereotypic feminine gender socialization may play an important determinant for anger suppression, which subsequently can lead to thermal discomfort from cold extremities and prolonged sleep onset latency.

Mismatch and conflict: neurophysiological and behavioral evidence for conflict priming.

Conflict-related cognitive processes are critical for adapting to sudden environmental changes that confront the individual with inconsistent or ambiguous information. Thus, these processes play a crucial role to cope with daily life. Generally, conflicts tend to accumulate especially in complex and threatening situations. Therefore, the question arises how conflict-related cognitive processes are modulated by the close succession of conflicts. In the present study, we investigated the effect of interactions between different types of conflict on performance as well as on electrophysiological parameters. A task-irrelevant auditory stimulus and a task-relevant visual stimulus were presented successively. The auditory stimulus consisted of a standard or deviant tone, followed by a congruent or incongruent Stroop stimulus. After standard prestimuli, performance deteriorated for incongruent compared to congruent Stroop stimuli, which were accompanied by a widespread negativity for incongruent versus congruent stimuli in the event-related potentials (ERPs). However, after deviant prestimuli, performance was better for incongruent than for congruent Stroop stimuli and an additional early negativity in the ERP emerged with a fronto-central maximum. Our data show that deviant auditory prestimuli facilitate specifically the processing of stimulus-related conflict, providing evidence for a conflict-priming effect.

Cold extremities and difficulties initiating sleep: evidence of co-morbidity from a random sample of a Swiss urban population.

Difficulties initiating sleep (DIS) can frequently occur in psychiatric disorders but also in the general population. The primary vasospastic syndrome is a functional disorder of vascular regulation in otherwise healthy subjects complaining of thermal discomfort from cold extremities (TDCE). Laboratory studies have shown a close relationship between long sleep onset latency and increased distal vasoconstriction in healthy young subjects. Considering these findings, the aims of the Basel Survey were to assess the prevalence rates for DIS and TDCE and to determine whether both symptoms can be associated in the general population. In a random population sample of Basel-Stadt, 2800 subjects (age: 20-40 years) were requested to complete a questionnaire on sleep behavior and TDCE (response rate: 72.3% in women, n = 1001; 60.0% in men, n = 809). Values of DIS and TDCE were based on questionnaire-derived scores. In addition, TDCE was externally validated in a separate group of subjects (n = 256) by finger skin temperature measurements--high TDCE values were significantly associated with low finger skin temperature. A total of 31.1% of women and 6.9% of men complain of TDCE. In contrast, prevalence rates of DIS were only slightly higher in women in comparison to men (9.3% versus 6.7%, P < 0.1). Irrespective of gender, each seventh subject complaining of TDCE had concomitant DIS and the relative risk in these subjects was approximately doubled. Therefore, a thermophysiological approach to DIS may be relevant for its differential diagnosis and its treatment.

Melatonin reduces arousal and startle responsiveness without influencing startle habituation or affective startle modulation in young women.

Melatonin has been suggested to affect human emotion, but conflicting evidence exists. Therefore, we tested the effect of a single dose of a 4 mg prolonged release formulation of melatonin on a biologically based model of emotional processing. Affective modulation of acoustic white noise startle (103 dB) by emotional slides selected from the International Affective Picture System (IAPS) was assessed in 16 healthy young women twice, in a double-blind, placebo-controlled, balanced cross-over design. Melatonin significantly reduced startle responsiveness, but did not impact affective startle modulation, nor startle habituation. Melatonin significantly reduced arousal ratings and induced a parasympathetically dominated heart rate variability pattern indicative of a non-aroused state. We conclude that melatonin reduces arousal and startle responsiveness. However, no evidence for a direct emotion-modulating effect of melatonin was found in this healthy cohort.

Influence of timed nutrient diet on depression and light sensitivity in seasonal affective disorder.

Seasonal Affective Disorder (SAD) patients crave and eat more carbohydrates (CHO) in fall-winter when depressed, especially in the evenings, and feel energetic thereafter. Evening CHO-rich meals can phase delay circadian rhythms, and glucose increases retinal response to light. We studied timed CHO- or protein-rich (PROT) diet as a putative therapy for SAD. Unmedicated, DSM-IV-diagnosed depressed women with SAD (n=22, 19-63 yrs) in the follicular phase of the menstrual cycle (present in 19) were randomized to nine days of eating approximately 1600 kcal of either CHO before 12:00 h (n=9), CHO after 18:00 h (n=6), or PROT after 18:00 h (n=7); only water was allowed for the rest of the day. Measurements included the depression questionnaire SIGH-SAD (with 21-item Hamilton depression subscale), Eating Behavior Questionnaire (DEBQ), percentage fat (by bioimpedancemetry), clinical biochemistry (glucose, cholesterol, triglycerides, TSH, T4, cortisol), and electroretinogram (ERG). No differential effects of diet were found on any of the studied parameters (except DEBQ). Clinically, participants improved slightly; the 21-HDRS score (mean+/-SD) decreased from 19.6+/-6.4 to 14.4+/-7.4 (p=.004). Percent change correlated significantly with menstrual day at diet onset (mood improved the first week after menstruation onset), change in available sunshine (more sunlight, better mood), and initial percentage fat (fatter patients improved more). Scotopic ERG amplitude was diminished after treatment (p=.025, three groups combined), probably due to greater exposure to sunshine in 14/22 subjects (partial correlation analysis significant). Keeping in mind the limitations of this ambulatory study (i.e., inability to control outdoor light exposure, small number of participants, and briefness of intervention), it is suggested that the 25% clinical improvement (of the order of magnitude of placebo) is not related to nutrient diet or its timing, but rather to natural changes during the menstrual cycle, available sunshine, and ease of dieting for fatter patients.

Chronobiological characterization of women with primary vasospastic syndrome: body heat loss capacity in relation to sleep initiation and phase of entrainment.

Women with primary vasospastic syndrome (VS), but otherwise healthy, exhibit a functional disorder of vascular regulation (main symptom: cold extremities) and often suffer from difficulties initiating sleep (DIS). Diverse studies have shown a close association between distal vasodilatation before lights off and a rapid onset of sleep. Therefore, we hypothesized that DIS in women with VS could be due to a reduced heat loss capacity in the evening, i.e., subjects are physiologically not ready for sleep. The aim of the study was to elucidate whether women having both VS and DIS (WVD) or not (controls) show different circadian characteristics (e.g., phase delay of the circadian thermoregulatory system with respect to the sleep-wake cycle). Healthy young women (n = 9 WVD and n = 9 control) completed a 40-h constant routine protocol (adjusted to habitual bedtime) before and after an 8-h sleep episode. Skin temperatures [off-line calculated as distal-proximal skin temperature gradient (DPG)] and core body temperature (CBT; rectal) were continuously recorded. Half-hourly saliva samples were collected for melatonin assay and subjective sleepiness was assessed on the Karolinska Sleepiness Scale (KSS). Compared with control, WVD showed no differences in habitual bed times, but a 1-h circadian phase delay of dim light-melatonin onset (hours after lights on: WVD 14.6 +/- 0.3 h; control 13.5 +/- 0.2 h; P = 0.01). Similar phase shifts were observed in CBT, DPG, and KSS ratings. In conclusion, WVD exhibit a phase delay of the endogenous circadian system with respect to their habitual sleep-wake cycle, which could be a cause of DIS.

The thermophysiological cascade leading to sleep initiation in relation to phase of entrainment.

This article reviews circadian thermoregulation in relation to sleep induction and phase of entrainment in the light of the comprehensive thermophysiological and chronobiological concepts of Jürgen Aschoff. The idea that temperature and sleep are interrelated is based on evolutionary history. Mammalian sleep developed in association with endothermy, and all species, independent of temporal niche, usually sleep during the circadian trough of their core body temperature (CBT) rhythm. The circadian pattern of CBT results from the balance between heat production and heat loss, the latter being relevant for sleep induction. Sleep under entrained conditions is typically initiated on the declining portion of the CBT curve when its rate of change and body heat loss is maximal. Body heat loss before lights off, via selective vasodilatation of distal skin regions, promotes sleepiness and the rapid onset of sleep. This thermophysiological effect represents the cement between the circadian clock and the sleep-wake cycle, and in turn determines phase of entrainment (Psi) and sleep onset latency (SOL). These interrelationships have been recently studied in a particular subset of the general population, mainly women, who suffer from cold hands and feet (the so-called vasospastic syndrome, VS). Women with VS exhibit not only a lower capacity to lose heat during the daytime but also a prolonged SOL, a disturbed Psi of the circadian clock with respect to the sleep-wake cycle and psychologically, a disposition to turn experienced anger inwards. This naturalistic model leads us to a more general conclusion that regulation of distal skin blood flow may have clinical relevance for insomnia, in particular sleep onset insomnia.