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Biomedical subjects

G A Kerkhof

Publications and source records attributed to G A Kerkhof.

At least 19 recordsLinked to original sources

Weak 24-h periodicity of body temperature and increased plasma vasopressin in melancholic depression.

Earlier work has shown that plasma vasopressin levels of depressed patients were higher than those of healthy controls. The aim of the present study was to determine whether plasma vasopressin levels were correlated to parameters of the circadian rhythm. Forty-one patients with major depression and twenty-five controls participated in a case-control design under natural circumstances in a field study to investigate plasma vasopressin levels three times daily, circadian motor activity, and the 24-h periodicity of body temperature for five consecutive 24-h periods. Temperature measurements consisted of at least five, but mostly six or more measurements every 24 h. Twenty-two percent of the patients, but none of the controls lacked 24-h periodicity of body temperature. In melancholic patients increased vasopressin levels in plasma correlated with a weak 24-h periodicity of body temperature. The role of vasopressin is discussed in the light of the present findings.

Adult↗

Repeated assessment of the endogenous 24-hour profile of blood pressure under constant routine.

The impact of environmental and behavioral factors on the 24-h profile of blood pressure (BP) has been well established. Various attempts have been made to control these exogenous factors, in order to investigate a possible endogenous circadian variation of BP. Recently, we reported the results of the first environmentally and behaviorally controlled laboratory study with 24-h recordings of BP and heart rate (HR) during maintained wakefulness. In this constant-routine study, a pronounced endogenous circadian rhythm of HR was found, but circadian variation of BP was absent. This result suggested that the circadian rhythm of BP observed in earlier controlled studies, with sleep allowed, was evoked by the sleep-wake cycle as opposed to the endogenous circadian pacemaker. In order to verify our previous finding during maintained wakefulness, we repeated the experiment five times with six normotensive, healthy young subjects. Statistical analyses of the hourly measurements of BP and HR confirmed the replicable presence of an endogenous circadian rhythm of HR, as well as the consistent absence of an endogenous circadian variation of BP. Thus, this study provided additional evidence that the 24-h profile of BP--as observed under normal circumstances--is the sole result of environmental and behavioral factors such as the occurrence of sleep, and has no endogenous circadian component.

Adolescent↗

Genetic analysis of morningness and eveningness.

We studied the influence of genetic factors on individual differences in morningness-eveningness in a sample of Dutch twin families. Data were collected from adolescent twins (mean age 17.8 yr) and their parents (mean age of fathers 48.0 yr and of mothers 46.0 yr) and a sample of older twins (mean age 46.5 yr). Scores on morningness-eveningness were rated on a 5-point scale. Parents were more morning oriented than their children, and women were more morning oriented than men. With a twin-family study, separation of genetic and environmental influences on variation in morningness-eveningness is possible. Including parents and older twins in the study makes it possible to explore generation differences in these effects. The correlation between monozygotic twins was more than twice the correlation between dizygotic twins. This indicates that genetic effects may not operate in an additive manner. Therefore, a model that included genetic dominance was explored. Biometrical model fitting showed no sex differences for the magnitude of genetic and environmental factors. The total heritability--the sum of additive and nonadditive genetic influences--for morningness-eveningness was 44% for the younger generation and 47% for the older generation. However, the genetic correlation between the generations turned out to be lower than 0.5, suggesting that different genes for morningness-eveningness are expressed in both generations.

Adolescent↗

Melatonin for chronic sleep onset insomnia in children: a randomized placebo-controlled trial.

To establish the efficacy of melatonin treatment in childhood sleep onset insomnia, 40 elementary school children, 6 to 12 years of age, who suffered more than 1 year from chronic sleep onset insomnia, were studied in a double-blind, placebo-controlled study. The children were randomly assigned to receive either 5-mg melatonin or placebo. The study consisted of a 1-week baseline, consecutively followed by a 4-week treatment period. After that period, treatment was continued if the parents wished so. The study's impact was assessed by measurements of lights-off time, sleep onset, and wake-up time, recorded in a diary (n = 33). Sleep onset was also recorded with an actigraph (n = 25). Endogenous dim light melatonin onset was measured in saliva (n = 27). Sustained attention was evaluated with the Bourdon-Vos reaction time test (n = 36). In the melatonin group, mean (95% CI) lights-off time advanced 34 (6-63) minutes, diary sleep onset 63 (32-94) minutes, actigraphic sleep onset 75 (36-114) minutes, and melatonin onset 57 (24 to 89) minutes; total sleep time increased 41 (19-62) minutes. In the placebo group, these parameters did not shift significantly. The change during the 4-week treatment period differed between the treatment groups significantly as to lights-off time, diary and actigraphic sleep onset, sleep duration, and melatonin onset. There were no significant differences between the treatment groups in the change of sleep latency, wake-up time, and sustained attention reaction times. Mild headache occurred in 2 children during the first 2 days of the melatonin treatment. Eighteen months after the start of the trial, in 13 of the 38 children who could be followed up, melatonin treatment was stopped because their sleep problem was solved and in 1 child because sleep was not improved. Twelve children used melatonin 5 mg, the other 1.0 to 2.5 mg. One child developed mild generalized epilepsy 4 months after the start of the trial. The results show that melatonin, 5 mg at 6 PM, was relatively safe to take in the short term and significantly more effective than placebo in advancing sleep onset and dim light melatonin onset and increasing sleep duration in elementary school children with chronic sleep onset insomnia. Sustained attention was not affected.

Child↗

Effects of melatonin on the quality of life in patients with delayed sleep phase syndrome.

OBJECTIVE: The purpose of this study was to compare health-related quality of life of delayed sleep phase syndrome (DSPS) patients with a random Dutch sample and four samples of patients with other chronic conditions. We also investigated the effectiveness of treatment with 5 mg of melatonin on the quality of life of DSPS patients. METHODS: Forty-three DSPS patients completed a quality-of-life questionnaire (Medical Outcome Study Short Form-36 [MOS SF-36] health survey) just before and 2-9 months after participation in a clinical trial involving the administration of melatonin. Scores were compared with responses to the same survey by a random Dutch sample and by patients with sleep apnea, clinical depression, migraine, and osteoarthritis. RESULTS: MOS SF-36 scales scores were significantly lower in DSPS patients relative to age- and gender-adjusted norms for the Dutch sample. Some health dimensions were more affected, and others less affected, by DSPS compared with the other chronic conditions. Melatonin treatment improved all scales except the scale "role due to emotional problems." CONCLUSION: DSPS has a unique significant quality-of-life burden that seems to be improved by treatment with melatonin.

Adult↗

Age differences in sleep-wake behavior under natural conditions.

Differences in lifestyle may account for a considerable portion of the reported age-related changes in overt circadian rhythmicity. By instructing a group of healthy, noninstitutionalized, elderly subjects and a group of young adults to keep a sleep-wake log for a period of two weeks, and to wear an activity monitor for an overlapping period of 11 days, we attempted to assess age-related differences in the habitual sleep-wake behavior, in particular its day-to-day variability. Four clusters of coherent variables were constructed, reflecting (1) circadian phase, (2) variability of sleep-wake behavior, (3) sleep-wake continuity and (4) subjective sleep-wake quality. The results showed that, in comparison with the young subjects, the elderly had a relatively advanced and more regular sleep-wake pattern, reported more midnight awakening and did not differ in their subjective sleep evaluation. In spite of a greater regularity in their lifestyle (which would favor a larger amplitude of the overt circadian rhythmicity) oral temperature measurements showed some evidence of a weakened 24-h periodicity in the elderly.

Adolescent↗

Plasma arginine vasopressin and motor activity in major depression.

BACKGROUND: Previously, we found that mean plasma concentrations of arginine vasopressin (AVP), but not of oxytocin (OT), were higher in depressed patients than in healthy controls. Plasma AVP concentrations were positively correlated to clinically rated psychomotor retardation. To further explore this previously reported relation we studied psychomotor retardation by means of an activity monitor, which is a more fine-focused and more objective instrument to analyze motor retardation than a clinical rating scale. METHODS: Plasma AVP and OT concentrations, and day- and nighttime wrist activity were measured in 48 in- and outpatients with major depression and 30 healthy controls during a period of 5 consecutive days and nights. RESULTS: Principal components analysis revealed three components of motor activity: motor activity during wakefulness, motor activity during sleep, and the awake/sleep time ratio. In patients and controls an inverse relationship between plasma AVP concentrations and motor activity during wakefulness was found. Patients with elevated AVP plasma levels showed increased motor activity during sleep. CONCLUSIONS: These results suggest that high plasma AVP levels are related to the clinical picture of daytime psychomotor retardation and nighttime motor activity in major depression. Mean plasma OT concentrations were not related to measures of motor activity.

Adult↗

The validity of the Dutch Sleep Disorders Questionnaire (SDQ).

The Sleep Disorders Questionnaire (SDQ) is a 176-item questionnaire designed to diagnose the presence of common sleep disorders. This study set out to assess the validity of a Dutch translation of the SDQ. Scores on 145 questionnaires were analyzed. A cluster analysis of these scores revealed the following clusters: healthy, depression, insomnia, narcolepsy, and apnea. The cluster classification proved correct for 67% of the subjects, as determined on the basis of polysomnography. These results show that the Dutch SDQ is a reasonably valid instrument for diagnosing sleep disorders.

Adolescent↗

Absence of endogenous circadian rhythmicity in blood pressure?

Currently available evidence reveals a predominant role of exogenous (so-called "masking") factors in the 24 h variation of blood pressure in humans. The existence of a (minor) endogenous circadian factor cannot be excluded, however. This possibility was tested by applying the rigorous unmasking conditions of the constant-routine protocol, that is, strict bed rest in a separate bedroom, total sleep deprivation, constant ambient temperature and illumination, and hourly equicaloric food and liquid intake. Twenty-five normotensive young individuals were subjected to a 26 h constant-routine procedure while hourly measurements were made of their blood pressure and heart rate. Repeated-measures analysis of variance failed to show a significant 24 h variation of blood pressure. The power of this test appeared satisfactorily high (>0.95). Heart rate, however, exhibited a significant circadian pattern, with a range of 6.7 beats/min (10% of the 24 h mean value). Moreover, the timing of the 24 h heart rate curves differed significantly between so-called morning (n = 10) and evening (n = 9) individuals. Mean peak values for the morning-types occurred at 11 AM, for the evening types nearly 6 h later. In conclusion, no evidence was found for the involvement of a circadian oscillator in the regulation of blood pressure.

Adult↗

Delayed sleep phase syndrome: A placebo-controlled cross-over study on the effects of melatonin administered five hours before the individual dim light melatonin onset.

In a double-blind placebo-controlled cross-over study, 30 patients with Delayed Sleep Phase Syndrome (DSPS) were included, of whom 25 finished the study. Melatonin 5 mg was administered during two weeks in a double-blind setting and two weeks in an open setting successively or interrupted by two week of placebo. The study's impact was assessed by measurements of the 24-h curves of endogenous melatonin production and rectal temperature (n = 14), polysomnography (n = 22), actigraphy (n = 13), sleep log (n = 22), and subjective sleep quality (n = 25). Mean dim light melatonin onset (DLMO) (+/- SD), before treatment, occurred at 23.17 hours (+/- 138 min). Melatonin was administered five hours before the individual DLMO. After treatment, the onset of the nocturnal melatonin profile was significantly advanced by approximately 1.5 hour. Body temperature trough did not advance significantly. During melatonin use, actigraphy showed a significant advance of sleep onset and polysomnography, a significant decreased sleep latency. Sleep architecture was not influenced. During melatonin treatment patients felt significantly more refreshed in the morning. These results show that analysis of DLMO of patients suffering from DSPS is important both for diagnosis and therapy. These results are discussed in terms of the biochemistry of the pineal.

Adult↗

Melatonin-responsive headache in delayed sleep phase syndrome: preliminary observations.

The occurrence of headache and its change after treatment with melatonin 5 mg were studied in 30 patients with delayed sleep phase syndrome. The medication was taken 5 hours before the endogenous nocturnal plasma melatonin concentration had reached 10 pg/mL. Three women (aged 14, 14, and 23 years) suffered from chronic tension-type headache. Their headache disappeared within 2 weeks after the start of treatment with melatonin. One 54-year-old man suffered from disabling migraine attacks without aura, twice a week. After starting melatonin treatment, only three migraine attacks were reported in 12 months. Ever since his 40s, a 60-year-old man complained of cluster headache episodes lasting about 2 months, twice a year. In the year since starting melatonin treatment, only one 5-day cluster episode occurred. Nocturnal melatonin secretion in the patients with delayed sleep phase syndrome and headache did not differ significantly from that in the patients with the sleep disorder but without headache. Melatonin may be helpful in patients with headache who are suffering from delayed sleep phase syndrome. Its effectiveness may be due to modification of vascular and nociceptive systems or to its chronobiological action which adjusts the patient's biological clock to his/her life-style.

Adolescent↗

The 24-hour variation of mood differs between morning- and evening-type individuals.

This study investigated a 24-hour variation of subjective mood in 16 healthy Morning-type and 13 Evening-type subjects as defined by the time of day at which their oral temperature curve reached its maximum. The subjects were instructed to use a sleep-wake logbook, in which they kept daily records of the ratings of their mood and alertness for a period of two consecutive weeks. For mood as well as for alertness analysis of variance indicated significant interactions between Morning and Evening-types and time of day. It is concluded that a pronounced diurnal variation of mood can be observed in healthy individuals, which differs between Morning-type and Evening-type subjects.

Adult↗

Absence of seasonal variation in the phase of the endogenous circadian rhythm in humans.

Humans may be subject to seasonal variations, as evidenced by the existence of seasonal affective disorder (SAD) and midwinter insomnia. However, some recent studies have shown that the seasonal variation in the phase of the circadian rhythm is relatively weak in healthy humans. In the present study, evidence is found that there is no seasonal variation in the phase of the endogenous circadian rhythm at all. Body temperature, cortisol excretion, and subjective alertness of six subjects recorded under constant routine conditions showed no systematic seasonal variation in circadian phases. This finding indicates that secondary zeitgebers blocked or counterbalanced the seasonal variation in the entrainment effect of the natural photoperiod. The human being may live in an environment in which the photoperiod has lost its status of primary zeitgeber.

Adolescent↗

Seasonal covariation of the circadian phases of rectal temperature and slow wave sleep onset.

There is a scarcity of well-controlled studies of the seasonal variation in circadian rhythmicity. In the present study, the circadian phase of rectal temperature and the onset of slow wave sleep were studied in a series of twelve 24-h experiments, one each month of the year, for six healthy subjects under controlled conditions in a climatic chamber. In winter, as compared with summer, the average circadian rhythm of rectal temperature was phase delayed by 45 min, and the average onset of slow wave sleep was phase delayed by 40 min. The temporal relationship between the circadian phase of rectal temperature and the timing of slow wave sleep was maintained throughout the year. Habitual rising and retiring times covaried as well. Furthermore, the circadian rhythm of rectal temperature followed the timing of the photoperiod across the year, but had a much smaller range of seasonal variation. Apparently, the seasonal variation in the photoperiodic zeitgeber is largely compensated for by the stabilizing influence of secondary zeitgebers. However, in healthy subjects some effect of photoperiodic variation can still be observed.

Adult↗

Morning-type and evening-type individuals differ in the phase position of their endogenous circadian oscillator.

In dealing with inter-individual phase differences in overt circadian rhythms, it is often difficult to distinguish the impact of the endogenous circadian oscillator from that of an individual's habitual lifestyle. In an attempt to resolve this uncertainty about the role of masking influences, two groups of subjects, morning-type and evening-types, were selected and monitored during entrained, habitual sleep-wake conditions and during 24 h of controlled wakefulness in a laboratory-based constant-routine procedure. Under both conditions significant differences were observed in the circadian phases of body temperature and subjective alertness. During constant routine mean between-group differences for these two variables were 2.21 and 4.28 h, respectively. Thus, evidence is provided for the endogenous nature of morningness-eveningness.

Adult↗

Suicidality, circadian activity rhythms and platelet serotonergic measures in patients with recurrent suicidal behaviour.

The circadian activity rhythm was assessed over a one-week period using a wrist-worn activity monitor in 59 patients with a history of recurrent suicide attempts. In 40 of these patients a second recording was made 6 months later. Platelet serotonin (5-HT) and monoamine oxidase-B activity (MAO) were measured. Suicidal ideation, borderline personality disorder and impulsiveness were associated with the absence of a clear 24-hour periodicity in motor activity. Depressive mood and hopelessness were associated with a less regular bed-in time and a lower daytime activity. Platelet 5-HT as well as MAO correlated negatively with the amplitude of the circadian activity rhythm. Our results support the suggested link between suicidality, altered circadian activity and serotonergic function.

Adult↗

Sleep disruption in Parkinson's disease. Assessment by continuous activity monitoring.

OBJECTIVE: To assess differences in activity and immobility during sleep between patients with Parkinson's disease (PD) and healthy subjects and to evaluate the relations of clinical variables with the motor activity measures in patients with PD. DESIGN: Survey, case series. SETTING: University hospital outpatient neurology department and urban population in Leiden, the Netherlands. Motor activity was recorded during 6 successive nights at home with a wrist-worn activity monitor. PARTICIPANTS: Eighty-nine patients with PD and 83 age-matched healthy controls. MAIN OUTCOME MEASURES: For each subject, three mean measures reflecting activity or immobility during the nocturnal period were calculated. RESULTS: Compared with the healthy elderly subjects, patients with PD have an elevated nocturnal activity level and an increased proportion of time with movement, indicating a more disturbed sleep. The mean duration of nocturnal immobility periods was similar for both groups. This measure, however, did reflect the self-reported disturbed sleep maintenance in both groups. The daily dose of levodopa or the use of dopamine agonists in patients not receiving levodopa, rather than disease severity, proved to be the best predictors of nocturnal activity. CONCLUSIONS: We hypothesize that in mildly to moderately affected patients with PD, levodopa or dopamine agonists cause sleep disruption by their effects on sleep regulation. In more severely affected patients, the beneficial effects of these drugs on nocturnal disabilities that cause sleep disruption in PD prevail.

Adult↗