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Biomedical subjects

D G Beersma

Publications and source records attributed to D G Beersma.

At least 19 recordsLinked to original sources

Extraocular light therapy in winter depression: a double-blind placebo-controlled study.

BACKGROUND: It has been hypothesized that the circadian pacemaker is phase delayed in seasonal affective disorder, (SAD) winter type, and that the phase advance resulting from morning ocular light accounts for the efficacy of light therapy. Extraocular light has been reported to produce phase-shifts of the human circadian pacemaker. This allows a double-blind, placebo-controlled study of light therapy in SAD. METHODS: Twenty-nine SAD patients participated. Clinical state was measured on days 1, 8, and 15 of the protocol. From days 4 through 8, 15 patients (4 M, 11 F) received extraocular light by fiberoptic illumination, and 14 (4 M, 10 F) placebo (no light) in the popliteal fossae, from 8 AM to 11 AM. In the evenings of days 3 and 8, the salivary dim light melatonin onset (DLMO) was assessed. Patients completed daily self-ratings on mood, alertness, and sleep. RESULTS: Both conditions showed a progressive improvement of clinical state over time. Between conditions, no significant differences were observed in clinical scores, the self-ratings on mood and alertness, and in timing of the DLMO before and directly after treatment. CONCLUSIONS: The response to extraocular light therapy in SAD patients did not exceed its placebo effect. Extraocular light did not induce a phase shift of the circadian pacemaker.

Adult↗

Seasonal changes in 24-h patterns of suicide rates: a study on train suicides in The Netherlands.

BACKGROUND: Annual patterns in suicide rates, peaking near the summer solstice, are well documented. It has been suggested that day length or total hours of sunshine has an impact on suicide rates. If these environmental factors are involved, we would expect changes in the daily pattern of suicide rates to occur over the year. To test this hypothesis, the 24-h patterns of suicide rate were investigated as a function of time of year. METHOD: Detailed information about the exact time of suicides in The Netherlands is only available for train suicides. Therefore, information concerning age, sex, time and place of occurrence of all verified train suicides over 15 years in The Netherlands (n=2830) was obtained from The Netherlands Railways archives. RESULTS: Daily patterns in train suicides show systematic variations of two kinds. First, independently of time of year, suicide rates at night drop to about 10% of their daytime values. Second, there are two daily peaks in the patterns which shift their timing over the year, with one peak occurring shortly after sunset, and the other one consistently occurring 9-10 h earlier. Both peaks shift with the 5.5-h shift in sunset time. LIMITATIONS: Train suicidal behaviour may not represent fatal suicidal behaviour in general. CONCLUSIONS: There are pronounced and systematic daily variations in train suicide rates in The Netherlands. One of these is related to clock time, the others are related to the light-dark cycle. The consistency of the patterns suggests a strong environmental influence on train suicidal behaviour. Research on 24-h patterns of suicide rates should control for time of year.

Adult↗

Body temperature and mood variations during forced desynchronization in winter depression: a preliminary report.

BACKGROUND: It has been suggested that certain abnormalities (e.g., in phase or amplitude) of the circadian pacemaker underlie seasonal affective disorder. METHODS: One male seasonal affective disorder patient (blind to the study design) participated in two 120-hour forced desynchrony experiments and was subjected to six 20-hour days, once during a depressive episode and once after recovery. Core body temperature was continuously measured. During wakefulness, the Adjective Mood Scale was completed at 2-hour intervals. RESULTS: Sleep-wake as well as pacemaker-related variations of mood were found, both when the subject was depressed and when he was euthymic. Compared with recovery, during the depressive episode the circadian temperature minimum and the circadian mood variation showed phase delays of approximately 1 and 2 hours, respectively. CONCLUSIONS: The data of this first seasonal affective disorder patient, participating in forced desynchrony experiments, may indicate a phase delay of the circadian pacemaker during a seasonal affective disorder episode.

Body Temperature↗

Prophylactic treatment of seasonal affective disorder (SAD) by using light visors: bright white or infrared light?

BACKGROUND: Thirty-eight patients with SAD participated in a light visor study addressing two questions. 1. Can the development of a depressive episode be prevented by daily exposure to bright light started before symptom onset in early fall and continued throughout the winter? 2. Does the light have to be visible in order to have beneficial effects? METHODS: Three groups participated in the study: I (n = 14) received bright white light (2500 lux); II, (n = 15) received infrared light (0.18 lux); III (n = 9, control group) did not receive any light treatment at all. RESULTS: Infrared light is just as effective as bright white light. Both are more effective than the control condition. CONCLUSIONS: Light visors can be effectively used to prevent the development of SAD. The fact that exposure to infrared light was as effective as exposure to bright white light questions the specific role of visible light in the treatment of SAD.

Adult↗

The prevalence of seasonal affective disorder in The Netherlands: a prospective and retrospective study of seasonal mood variation in the general population.

BACKGROUND: The aim of the present study was to assess the prevalence of seasonal affective disorder (SAD) in The Netherlands. METHODS: The subjects (n = 5356), randomly selected from community registers, were given the Seasonal Pattern Assessment Questionnaire and the Centre for Epidemiological Studies Depression Scale over a period of 13 months. The response rate was 52.6%. RESULTS: Three percent of the respondents met the criteria for winter SAD, 0.1% for summer SAD. The criteria for subsyndromal SAD, a milder form of SAD, were met by 8.5%, 0.3% of whom showed a summer pattern. Younger women received a diagnosis of SAD more often than men or older women. CONCLUSIONS: SAD subjects were significantly more often unemployed or on sick leave than other subjects. Respondents who met winter SAD criteria were significantly more depressed than healthy subjects, in both winter and summer. Finally, month of completion had no influence on the number of subjects meeting the SAD criteria.

Absenteeism↗

Seasonal affective disorder and latitude: a review of the literature.

BACKGROUND: The aim of the study is to investigate the relationship between the prevalence of SAD and latitude. METHODS: An overview of the epidemiological literature on the prevalence of SAD is given and studies relevant for the latitudinal dependency of prevalence will be analyzed and discussed. RESULTS: The mean prevalence of SAD is two times higher in North America compared to Europe. Over all prevalence studies, the correlation between prevalence and latitude was not significant. A significant positive correlation was found between prevalence and latitude in North America. For Europe there was a trend in the same direction. CONCLUSIONS: The influence of latitude on prevalence seems to be small and other factors like climate, genetic vulnerability and social-cultural context can be expected to play a more important role. Additional controlled studies taking these factors into account are necessary to identify their influence.

Adult↗

Effects of light exposure and sleep displacement on dim light melatonin onset.

The purpose of the study was to induce in two different ways, a phase-angle difference between the circadian pacemaker and the imposed sleep-wake cycle in humans, we intended to: (i) shift the circadian pacemaker by exposure to bright light and keep the timing of the sleep-wake cycle fixed; and (ii) keep the timing of the circadian pacemaker fixed by a constant light-dark cycle and displace sleep. We monitored dim light melatonin onset (DLMO), core body temperature and sleep. DLMO was delayed significantly after 3 days of a 3-h delayed sleep-phase when compared with 3 days of sleep at a normal or 3-h advanced sleep-phase. The shifts in DLMO were not accompanied by shifts in body temperature, changes in waking-up time or by a change in the duration of the first rapid eye movement (REM) sleep episode. Three days of light exposure in the morning or evening resulted in shifts in DLMO of similar magnitude, but this was accompanied by shifts in the rhythm of body temperature, changes in waking-up time and in the duration of the first REM sleep episode. We conclude that the changes observed after light exposure reflect shifts in the circadian pacemaker. In contrast, we propose that the changes observed in DLMO after sleep displacement are not mediated by the circadian pacemaker. These results raise some doubts about the reliability of DLMO as a marker of circadian phase in cases of sleep disturbances. Finally, we initiate a search for changes in sleep that might be responsible for the unexpected effects on DLMO.

Adult↗

Melatonin suppression by light in humans is maximal when the nasal part of the retina is illuminated.

This study investigated whether sensitivity of the nocturnal melatonin suppression response to light depends on the area of the retina exposed. The reason to suspect uneven spatial sensitivity distribution stems from animal work that revealed that retinal ganglion cells projecting to the suprachiasmatic nuclei (SCN) are unequally distributed in several species of mammals. Four distinct areas of the retinas of 8 volunteers were selectively exposed to 500 lux between 1:30 a.m. and 3:30 a.m. Saliva samples were taken before, during, and after light exposure in 1-h intervals. A significant difference in sensitivity was found between exposure of the lateral and nasal parts of the retinas, showing that melatonin suppression is maximal on exposure of the nasal part of the retina. The results imply that artificial manipulation of the circadian pacemaker to alleviate jet lag, to improve alertness in shift workers, and possibly to treat patients suffering from seasonal affective disorder should encompass light exposure of the nasal retina.

Adult↗

Accuracy of circadian entrainment under fluctuating light conditions: contributions of phase and period responses.

The accuracy with which a circadian pacemaker can entrain to an environmental 24-h zeitgeber signal depends on (a) characteristics of the entraining signal and (b) response characteristics and intrinsic stability of the pacemaker itself. Position of the sun, weather conditions, shades, and behavioral variations (eye closure, burrowing) all modulate the light signal reaching the pacemaker. A simple model of a circadian pacemaker allows researchers to explore the impact of these factors on pacemaker accuracy. Accuracy is operationally defined as the reciprocal value of the day-to-day standard deviation of the clock times at which a reference phase (0) is reached. For the purpose of this exploration, the authors used a model pacemaker characterized solely by its momentary phase and momentary velocity. The average velocity determines the time needed to complete one pacemaker cycle and, therefore, is inversely proportional to pacemaker period. The model pacemaker responds to light by shifting phase and/or changing its velocity. The authors assumed further that phase and velocity show small random fluctuations and that the velocity is subject to aftereffects. Aftereffects were incorporated mathematically in a term allowing period to contract exponentially to a stable steady-state value, with a time constant of 69 d in the absence of light. The simulations demonstrate that a pacemaker reaches highest accuracy when it responds to light by simultaneous phase shifts and changes of its velocity. Phase delays need to coincide with slowing down and advances with speeding up; otherwise, no synchronization to the zeitgeber occurs. At maximal accuracy, the changes in velocity are such that the average period of the pacemaker under entrained conditions equals 24 h. The results suggest that during entrainment, the pacemaker adjusts its period to 24 h, after which daily phase shifts to compensate for differences between the periods of the zeitgeber and the clock are no longer necessary. On average, phase shifts compensate for maladjustments of phase and velocity changes compensate for maladjustments of period.

Animals↗

Accuracy of human circadian entrainment under natural light conditions: model simulations.

The patterns of light intensity to which humans expose their circadian pacemakers in daily life are very irregular and vary greatly from day to day. The circadian pacemaker can adjust to such irregular exposure patterns by daily phase shifts, such as summarized in a phase response curve. It is demonstrated in this paper on the basis of computer simulations applying actually recorded human light exposure patterns that the pacemaker can substantially improve its accuracy by an additional response to light: For that purpose, it should additionally change its angular velocity (and consequently its period tau) in response to light. Reductions of tau in response to light in the morning and increases of tau in response to light in the evening can lead to an increase in entrained pacemaker accuracy with about 25%. Circadian pacemakers have evolved as accurate internal representations of external time, and investigated diurnal mammals all seem to respond to light by changing the period of their circadian pacemaker (in addition to shifting phase). The authors suggest that also human circadian systems take advantage of this possibility and that their pacemakers respond to light by shifting phase and changing period. As a consequence of this postulated mechanism, the simulations demonstrate that the period of the pacemaker under normally entrained conditions is 24 h. The maximum accuracy corresponds to a day-to-day standard deviation of the time of phase 0 of circa 15 min. This is considerably more accurate than the light signal humans usually perceive.

Adult↗

Forced desynchrony of circadian rhythms of body temperature and activity in rats.

The daily rhythm in body temperature is thought to be the result of the direct effects of activity and the effects of an endogenous circadian clock. Forced desynchrony (FD) is a tool used in human circadian rhythm research to disentangle endogenous and activity-related effects on daily rhythms. In the present study, we applied an FD protocol to rats. We subjected 8 rats for 5 days to a 20 h forced activity cycle consisting of 10 h of forced wakefulness and 10 h for rest and sleep. The procedure aimed to introduce a 10 h sleep/10 h wake cycle, which period was different from the endogenous circadian (about 24 h) rhythm. Of the variation in the raw body temperature data, 68-77% could be explained by a summation of estimated endogenous circadian cycle and forced activity cycle components of body temperature. Free-running circadian periods of body temperature during FD were similar to free-running periods measured in constant conditions. The applied forced activity cycle reduced clock-related circadian modulation of activity. This reduction of circadian modulation of activity did not affect body temperature. Also, the effects of the forced activity on body temperature were remarkably small.

Animals↗

Models of human sleep regulation.

Non-REM sleep deprivation and REM sleep deprivation both lead to specific rebounds, suggesting that these states fulfil physiological needs. In view of impaired performance after sleep deprivation, a recovery function of sleep seems likely. The timing of this recovery is restricted to a narrow time interval within the 24 hour day, i.e. the night. Generally, nocturnal sleep in humans is considered a consequence of the impact of the circadian pacemaker in the hypothalamus on sleep propensity. The interaction between the homeostatic recovery process and the circadian pacemaker has been modelled in the two-process model of sleep regulation. This model is used as a starting point in the present review. A series of refinements and several alternative models are discussed, both with respect to the quality of fit of theory and data, as well as with respect to the concepts behind the models.

Journal Article↗

Testing the hypothesis of a circadian phase disturbance underlying depressive mood in nonseasonal depression.

In a crossover design, 8 nonseasonal depressed subjects, selected on the presence of diurnal mood variations, and 8 sex- and age-matched controls were exposed to dim light (< 10 lux) in the evening (18:00-21:00 h) and bright light (2500 lux) in the morning (ML, 6:00-9:00 h), to dim light in the morning and bright light in the evening (EL), or to dim light both in the evening and in the morning (DL) during 3 consecutive days in each of these conditions. There were no initial phase differences between depressed and healthy subjects in the timing of dim light melatonin onset, sleep termination, and body temperature. The phase shifts after EL and ML in both healthy and depressed subjects were as expected on the basis of a human phase response curve. On average, there was no therapeutic effect of the light exposure in the depressed patients. Two patients improved, but these effects do not seem to be related to shifts in the circadian system.

Adult↗

No impact of physical activity on the period of the circadian pacemaker in humans.

The intrinsic period tau of the circadian pacemaker in humans was investigated by means of forced desynchrony. In this protocol, during 6 scheduled days, the sleep-wake alternation was forced to a period of 20h (i.e., 13.5h for wakefulness and 6.5h for sleep). Light intensity was kept below 10 lux. Three experiments were performed. In experiment 1, 12 subjects were free to spend the available time studying, watching videos, and reading books. In experiment 2, at 2h intervals, 11 subjects spent 6 half-hour sessions per subjective day cycling with minimal effort on a cycle trainer, resulting in an average increase of heart frequency of less than 10 beats per minute. In experiment 3, 11 subjects spent the same intervals of time cycling, but now during 20 minutes per session at an average heart rate of between 140 and 150 beats per minute. Core body temperature was measured continuously. A deconvolution technique discriminated the impact of the circadian pacemaker on body temperature from the impact of activities related to sleeping and waking. From this analysis, the period of the pacemaker was derived. We found the following results: experiment 1, tau = 24.30 +/- 0.36h; experiment 2, tau = 24.17 +/- 0.45h; experiment 3, tau = 23.98 +/- 0.42h. The trend of shorter tau at higher levels of physical activity was not statistically significant. We conclude that tau in humans, determined under conditions of forced desynchrony, is very close to 24h. The suggestion from the literature that single activity pulses would predominantly yield phase delays of the circadian pacemaker is not confirmed by these multiple pulse experiments because no lengthening of tau with increasing effort was observed.

Adult↗

Prediction of acute and late responses to light therapy from vocal (pitch) and self-rated activation in seasonal affective disorder.

It was hypothesized that pre-treatment activation plays a role in the response to light therapy in Seasonal Affective Disorder (SAD). In 55 SAD patients (DSMIII-R) energetic and tense activation was assessed before light therapy via self-rating (AD-ACL) and voice sound characteristics (mean pitch and variation in pitch). These variables were studied in relation to the "acute" response to 4 days of light therapy (30 min, 10000 lux) and to a "late" response (11 (10) days after light therapy had stopped). Acute response was defined as the percent change in 3 times daily self-rated depressed mood (AMS) with respect to the average of 4 baseline days. "Late" response was defined as the percent change in HRSD or AMS scores between baseline and 11 (10) days after light therapy. It was found that patients having high pitched voices with small variation in this pitch benefitted more from light therapy than the patients with low pitch and large variation in pitch levels. This effect was only significant after the first day of light exposure. No other significant relations were found between baseline activation and acute or late responses to light therapy. Hence, light therapy seems to give extra comfort in "tense" patients, who become rapid responders to light therapy.

Adult↗

Endogenous and exogenous components in the circadian variation of core body temperature in humans.

Core body temperature is predominantly modulated by endogenous and exogenous components. In the present study we tested whether these two components can be reliably assessed in a protocol which lasts for only 120 h. In this so-called forced desynchrony protocol, 12 healthy male subjects (age 23.7 +/- 1.4 y) were subjected one by one to an artificial light/dark cycle of 20 h (10 lux vs. darkness). Core body temperature was measured continuously. The temperature data were analysed by an iterative method based on the assumption that the endogenous and exogenous components contribute to body temperature in an additive way. The results show that the average temperature curve is an almost perfect addition of the two components. The endogenous component differs from a sinusoid, and the relative contributions of the endogenous and exogenous components to the raw temperature curves differ substantially between the subjects. The average amount of unexplained variance in the individual data was 17%. Averaging of the body temperature curves over subjects reduced the unexplained variance to only 2%. This reduction in unexplained variance upon averaging over subjects must be due to the fact that most of the variance is either differently dependent on circadian phase for the various subjects or not dependent on circadian phase at all. The circadian pacemaker component revealed an average value of tau of 24.30 +/- 0.36 h, which is consistent with recent findings in the literature. We conclude that a short forced desynchrony protocol is sufficient for the distinction between the masking and pacemaker components of core body temperature. The same protocol can be used to study the influence of these components on all kinds of other physiological and psychological signals.

Adult↗

Changes in EEG power density of non-REM sleep in depressed patients during treatment with trazodone.

Recently, it was hypothesized that acute or cumulative suppression of non-REM sleep intensity might be related to the therapeutic effects of antidepressants. This intensity has been proposed to be expressed in the EEG power density in non-REM sleep. In the present study, the relationship was examined between the changes of EEG power density in non-REM sleep and the changes in clinical state in 8 depressed patients during treatment with trazodone. A 1-week wash-out period was followed by 1 week of placebo administration, a medication period of 5 weeks and a 1-week placebo period. To minimize systematic influences of sleep duration and non-REM-REM sleep alterations, EEG power was measured over the longest common amount of non-REM sleep stages 2-4 (168.5 min), accumulated from sleep onset onwards. During trazodone treatment, the 13- and 14-Hz bins showed a significant reduction in EEG power. No clear-cut change, however, was observed in the EEG power of the delta frequency range (1-4 Hz) which is considered to be the principle manifestation of non-REM sleep intensity. Furthermore, no overall significant relationship between EEG power suppression and clinical improvement could be demonstrated.

Adult↗