Shift work is associated with extensively disordered sleep, especially when working nights.

Background: Shift work is generally associated with working and sleeping out of phase with the endogenous, circadian sleep-wake cycle. This exerts detrimental effects on sleep health. The present study aimed at evaluating the presence of short and long sleep as well as sleep disorders within a broad range of shift work schedules and elucidating the role of sociodemographic factors therein. Methods: A large dataset containing information on sleep was collected through advertisement in a Belgium newspaper (De Standaard). Adult, working individuals were selected (n = 37,662) and categorized based on their work schedule (regular day, early morning, evening, night, and rotating shift). In this cross-sectional study, prevalence rates of short sleep (≤6 h), long sleep (≥9 h) and sleep disorders (screened with Holland Sleep Disorders Questionnaire), and associations between these sleep variables and sociodemographics (age, sex, education, living companion(s)) were analyzed using binominal logistic regression analyses. Results: In the total sample all sociodemographic factors affected prevalences of short, long and disordered sleep, consistent with previous studies. Compared to day workers, shift workers more frequently reported short sleep, most prominently night workers (26 vs. 50%) (p < 0.001). Furthermore, all sleep disorders as well as sleep disorder comorbidity were more common in shift workers, again most pronounced in night workers (all p < 0.05). In night shift workers the level of education had the strongest associations with disturbed sleep with a two-fold higher prevalence of short and disordered sleep in low relative to academic educated groups (all p < 0.02). Conclusion: Shift work is related not only to curtailed sleep and shift work disorder, but also to a plethora of sleep disorders, including insomnia, sleep-related breathing disorders and sleep-related movement disorders. Our findings imply that education on coping strategies may be especially important for young and/or lower educated shift workers.

[Sleep-wake disorders and DSM-5]. / Slaap-waakstoornissen en DSM-5.

BACKGROUND: Most individuals with mental disorders complain about the problems they experience with sleeping and waking. It is becoming evident that careful diagnosis of sleep-wake disorders is of great importance for the prevention and treatment of mental disorders. Since the introduction of the DSM-IV, clinical scientific research has provided important new insights in this field. AIM: To find out whether the new classification of sleep-wake disorders in DSM-5 is likely to improve the diagnosis of disorders of this type. METHOD: We discuss the main changes in the DSM-5 classification of sleep- wake disorders, comparing the new version with the version in DSM-IV. RESULTS: Because considerable attention is being given to the symptom-orientated and dimensional approach, the classification of sleep-wake disorders in the DSM-5 is closer to current psychiatric practice and it does justice to the current scientific insights into the dimensional nature of psychiatric disorders. CONCLUSION: The DSM-5 classification takes recent scientific insights into account and might help to improve the diagnosis of sleep-wake disorders in psychiatry.

Virtual reality exposure therapy does not provide any additional value in agoraphobic patients: a randomized controlled trial.

BACKGROUND: A number of studies have demonstrated the efficacy of virtual reality exposure therapy (VRET) in specific phobias, but research in seriously impaired patients with agoraphobia is lacking. In this randomized controlled trial with patients with agoraphobia and panic disorder, VRET and exposure in vivo were compared in terms of outcome and processes involved. METHODS: Patients with panic disorder with agoraphobia (n = 55) were randomly assigned to receive 4 sessions of cognitive behavioral therapy (CBT) followed by either 6 sessions of VRET or 6 sessions of exposure in vivo or to a waiting list control condition. RESULTS: Analyses showed that both active treatment packages were significantly more effective than no treatment and that no differences between VRET and exposure in vivo were found in three out of four outcome measures. On the panic disorder severity scale, however, CBT plus exposure in vivo was more effective than CBT plus VRET. The results show clear synchrony of temporal processes involved in VRET and exposure in vivo on weekly avoidance measures and cognitive measures. Further, it was shown that initial changes in agoraphobic cognitions during the CBT phase predicted later changes in agoraphobic avoidance behavior. CONCLUSION: These data support the notion that therapeutic processes involved might be the same in VRET and exposure in vivo. However, given the slight superiority of exposure in vivo above VRET, the costs involved in the implementation of VRET and the lack of long-term follow-up, VRET cannot yet be recommended for patients with agoraphobia.

Effect of birth size and catch-up growth on adult blood pressure and carotid intima-media thickness.

AIMS: To investigate the effect of birth size and weight gain during childhood on blood pressure and carotid intima-media thickness (cIMT) in young adulthood. METHODS: The relationship of birth size with systolic blood pressure (SBP), diastolic blood pressure (DBP), and cIMT was investigated in 243 adults, aged 18­24 years. SBP, DBP, and cIMT were also analyzed in 4 subgroups: subjects either born small for gestational age with short stature (SGA-S) or with catch-up growth (SGA-CU), or born appropriate for gestational age with idiopathic short stature or with normal stature (controls). RESULTS: Adult weight SDS and fat mass were positively related to SBP and DBP, adjusted for birthweight SDS which was not related to SBP and DBP. Birth size was also not related to cIMT. Subgroup analyses showed no differences in blood pressure between subgroups, but cIMT was significantly greater in SGA-CU subjects than in controls after correction for age, gender and artery diameter. This difference became borderline significant after additional correction for smoking and SBP. CONCLUSION: Not birth size but childhood weight gain, especially fat mass, determines young adult blood pressure. Postnatal catch-up growth appears to have a greater influence on cardiovascular disease markers than birth size.

Fat mass and lipid profile in young adults born preterm.

CONTEXT: Associations between small size at birth and abnormal cardiovascular parameters in later life have been reported. It is, however, unknown whether the effect of a small size at birth on cardiovascular risk factors in later life is due to a small size for gestational age or due to prematurity. Due to advances in neonatal care, survival of preterm infants has significantly improved, and nowadays an increasing number of these children reach adulthood. It is, therefore, of increasing importance to assess the long-term effect of prematurity on determinants for cardiovascular disease. OBJECTIVE: The aim of the study was to assess the long-term effects of gestational age and particularly preterm birth on lipid levels and fat mass in early adulthood. DESIGN AND PATIENTS: A cross-sectional study was conducted with 455 healthy subjects, aged 18 to 24 yr; 167 preterm subjects were compared with 288 full-term subjects. OUTCOME MEASURE: Total fat mass, trunk fat mass, and limb fat mass were determined by dual-energy x-ray absorptiometry. Furthermore, fasting lipid levels (total cholesterol, low-density lipoprotein, triglyceride, apolipoprotein B, lipoprotein a, high-density lipoprotein, and apolipoprotein A-I) were measured. RESULTS: Preterm subjects had a significantly higher percentage of total fat mass, trunk fat mass, and limb fat mass than subjects born term. Furthermore, preterm subjects had significantly lower serum lipoprotein a levels and higher apolipoprotein A-I levels than term subjects. Multiple linear regression analyses to assess the association between gestational age and fat mass and lipid levels showed similar results. CONCLUSION: In our cohort of 455 young adults, preterm birth was associated with more total fat mass, trunk fat, and limb fat mass but a relatively favorable lipid profile.

Long-term impact of GH treatment during childhood on body composition and fat distribution in young adults born SGA.

CONTEXT: GH treatment of short children born small for gestational age (SGA) results in a decline in fat mass (FM) and an increase in lean body mass (LBM). It is, however, unknown whether these changes persist into adulthood. OBJECTIVE: Our objective was to assess the long-term impact of GH treatment during childhood on body composition and fat distribution. PATIENTS AND DESIGN: A total of 377 young adults participated in this cross-sectional study: 59 previously GH-treated young SGA adults compared to 52 untreated SGA adults with short stature (SGA-S), 161 SGA adults with spontaneous catch-up growth (SGA-CU), and 105 healthy normal-statured controls born appropriate for gestational age (AGA). OUTCOME MEASURES: Body composition and fat distribution were determined by dual-energy x-ray absorptiometry. RESULTS: Mean (SD) duration of GH treatment was 7.7 (2.4) yr and period after discontinuation 6.8 (1.8) yr. FM, fat distribution, and LBM of GH-treated SGA adults were not significantly different from that of untreated SGA-S adults. GH-treated SGA adults also had a similar FM and fat distribution as SGA-CU adults but a lower LBM. All SGA subgroups had a lower LBM and tended to have a higher FM than healthy AGA controls. CONCLUSION: Body composition and fat distribution of previously GH-treated SGA adults was similar to that of untreated SGA-S adults. GH-induced catch-up growth has no unfavorable effect on FM and fat distribution compared with spontaneous catch-up growth. However, our study shows that SGA adults in general may have a different body composition than healthy AGA controls.

Influence of preterm birth and small birth size on serum anti-Müllerian hormone levels in young adult women.

BACKGROUND/OBJECTIVES: Preterm birth has been associated with reduced reproduction rates, and controversies remain regarding the effect of being born small for gestational age (SGA) on ovarian function. Recent findings in young men showed no effect of preterm and SGA birth on testis function. We hypothesised that follicle pool size in young adult women is also not affected by preterm and SGA birth. DESIGN/METHODS: In 279 young women of the PROGRAM/PREMS study, aged 18-24 years, the influence of gestational age, birth length and birth weight on serum levels of anti-Müllerian hormone (AMH) was analysed with multiple regression modelling. Additionally, AMH levels were analysed in preterm- versus term-born females and in three subgroups: females born SGA with either short stature or catch-up growth (SGA-CU), and females born term and appropriate for gestational age with normal stature (AGA controls). RESULTS: Preterm and SGA birth did not affect AMH and other hormone levels. Older age at menarche and oral contraceptive pill use (OC-use) were related to lower AMH levels, and maternal smoking during gestation was related to higher AMH levels. After correction for maternal smoking, lower socioeconomic status (SES) was associated with lower AMH levels. In subgroup comparisons, SGA-CU women showed higher AMH levels than AGA controls, also after adjustment for several factors. CONCLUSION: Preterm and SGA birth did not affect AMH levels. Factors associated with serum AMH levels were OC-use, age at menarche, maternal smoking during gestation and SES. We conclude that preterm- and/or SGA-born females are not likely to have a reduced follicle pool size.

Subjective sleep efficiency of hemodialysis patients.

BACKGROUND: Sleep disturbances have a major influence on quality of life. A commonly used measure of sleep disturbances is sleep efficiency. The purpose of this study was to investigate the prevalence of decreased subjective sleep efficiency in hemodialysis patients. An additional goal was to identify clinical, dialysis or laboratory parameters that are independently associated with decreased sleep efficiency. METHODS: Adult stable hemodialysis patients (n = 112) filled out a sleep questionnaire during a three day investigation period. In addition, healthy control subjects (n = 44) filled out the same questionnaire. From this questionnaire sleep efficiency (ratio of total sleep time to time spent in bed) was derived as a measure for sleep disturbances in this population. Laboratory, demographic and dialysis data were collected during the investigation period. For statistical analysis linear regression models were used. RESULTS: Median subjective sleep efficiency in hemodialysis patients was 80%, which was significantly less compared to the median subjective sleep efficiency of control subjects of 88% (p pound 0.05). Approximately 40% of the patients used sleep medication. However, less than 20% of them indicated improved sleep behavior when using these drugs. Elevated levels of phosphate and urea correlated independently with impaired sleep efficiency. Hemoglobin levels between 10 and 12 g/dl were associated with better sleep efficiency. CONCLUSION: In conclusion, decreased sleep efficiency was frequently reported in hemodialysis patients and can be associated with biochemical parameters. Hemoglobin, phosphate and urea levels can affect subjective sleep efficiency.

Fat mass and apolipoprotein E genotype influence serum lipoprotein levels in early adulthood, whereas birth size does not.

BACKGROUND/OBJECTIVES: An association between an unfavorable lipid profile and low birth weight has been reported, although this association remains controversial. We hypothesized that birth size does not have any influence on serum lipid levels but fat accumulation during childhood has. METHODS: In the PROgramming factors for GRowth And Metabolism study, a cohort of 297 young adults, aged 18-24 yr, the influence of clinical parameters on total cholesterol, triglycerides, low-density lipoprotein, high-density lipoprotein, lipoprotein a, and apolipoprotein (apo) A-1 and apoB was analyzed with multiple regression modeling. In addition, differences in these lipid levels and ApoE genotype prevalence were analyzed in four subgroups: young adults either born small for gestational age with short stature or with catch-up growth, or born appropriate for gestational age with idiopathic short stature or with normal stature (controls). RESULTS: Birth length sd score (SDS) and birth weight SDS were no significant determinants of the serum lipid levels, whereas gender, ApoE genotype, adult height SDS, adult weight SDS, and fat mass were. Comparison of the subgroups showed that small for gestational age with short stature subjects had a significantly higher apoB than controls. There were no other significant differences in lipid levels or ApoE genotype prevalence among the four subgroups. CONCLUSIONS: ApoE genotype is an important genetic determinant of lipid levels in young adulthood. Furthermore, fat accumulation during childhood significantly determines serum lipid levels, whereas birth size has no significant contribution. For public health practice, this means that parents and their children need to be informed about the risks of fat accumulation during childhood.

Temperature profiles, and the effect of sleep on them, in relation to morningness-eveningness in healthy female subjects.

There were 15 healthy female subjects, differing in their position on the "morningness-eveningness" scale, studied for 7 consecutive days, first while living a sedentary lifestyle and sleeping between midnight and 08:00 and then while undergoing a "constant routine." Rectal temperature was measured at regular intervals throughout this time, and the results were subjected to cosinor analysis both before and after "purification" for the effects of physical activity. Results showed that there was a phase difference in the circadian rhythm of core temperature that was associated with the morningness score, with calculations that "morning types" would be phased earlier than "evening types" by up to about 3 h. This difference in phase (which was also statistically significant when the group was divided by a median split into a "morning group" and an "evening group") could not be attributed to effects of waking activity and existed in spite of the subjects keeping the same sleep-wake schedule. Moreover, it persisted when the subjects' data had been purified and when the data were obtained from the constant routine. That is, there was an endogenous component to this difference in phase of the core temperature. The morning group also showed a greater fall of core temperature during sleep; this was assessed in two ways, the main one being a comparison of constant routine and nychthemeral data sets after correction for any effects of activity. Even though the morning group was sleeping at a later phase of their circadian temperature rhythm than was the evening group, neither group showed a fall of temperature due to sleep that varied with time elapsed since the temperature acrophase. It is concluded that another factor that differs between morning and evening types is responsible for this difference.

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.

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.

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.

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.

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.

Circadian phase estimation of chronic insomniacs relates to their sleep characteristics.

The significance of the phase of circadian rhythmicity for the diagnosis of sleep disturbance was investigated in a group of 80 chronic insomniacs (59 females; mean age 34.8, range 18-59 years). In order to stay close to common clinical practice, data were collected by means of two-week sleep diaries in combination with repeated measurements of subjective alertness and oral temperature. Special measures were taken to minimize the impact of masking upon the temperature measurements. In addition, wrist activity was monitored for an overlapping period of 11 days. Measurements of oral temperature and subjective alertness were fitted with 3 (rd) -degree polynomials, for which the peak times (times of maximum) were identified. Principal Components Analysis of these peak times and the times of bed-in and wake-up for all subjects revealed that the phase estimates for the alertness and the sleep-wake rhythms had a strong interrelationship, which was independent from the temperature phase. Using the 25- and the 75-percentiles of the frequency distribution of the temperature peak times as boundaries, the subjects were classified into early (N = 18), middle (N = 37) and late (N = 19) temperature phase subgroups, which had mean peak times of 14:08 h, 17:43 h and 20:09 h, respectively. Comparisons between the early phase and the late phase subgroups showed that a significant overall MANOVA effect was mainly due to differences in total sleep time (early < late) as calculated from the log, and to differences in the mean nocturnal actigraphic count (early> late). Moreover, the subjective estimates of sleep latency (early < late) and wake after sleep onset (early > late) tended to differ between the two subgroups. The main result of this study, i.e., that insomniacs with a relatively advanced temperature phase had a relatively shorter and more restless sleep, while insomniacs with a relatively delayed temperature phase tended to experience a relatively long sleep latency, supports the conclusion that the addition of oral temperature measurements to a sleep/wake log extends its diagnostic and therapeutic applicability.

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.

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.

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.