Effect of Hibiscus syriacus Linnaeus extract and its active constituent, saponarin, in animal models of stress-induced sleep disturbances and pentobarbital-induced sleep.

Treatment of sleep disorders promotes the long-term use of commercially available sleep inducers that have several adverse effects, including addiction, systemic fatigue, weakness, loss of concentration, headache, and digestive problems. Therefore, we aimed to limit these adverse effects by investigating a natural product, the extract of the Hibiscus syriacus Linnaeus flower (HSF), as an alternative treatment. In the electric footshock model, we measured anxiety and assessed the degree of sleep improvement after administering HSF extract. In the restraint model, we studied the sleep rate using PiezoSleep, a noninvasive assessment system. In the pentobarbital model, we measured sleep improvement and changes in sleep-related factors. Our first model confirmed the desirable effects of HSF extract and its active constituent, saponarin, on anxiolysis and Wake times. HSF extract also increased REM sleep time. Furthermore, HSF extract and saponarin increased the expression of cortical GABAA receptor α1 (GABAAR α1) and c-Fos in the ventrolateral preoptic nucleus (VLPO). In the second model, HSF extract and saponarin restored the sleep rate and the sleep bout duration. In the third model, HSF extract and saponarin increased sleep maintenance time. Moreover, HSF extract and saponarin increased cortical cholecystokinin (CCK) mRNA levels and the expression of VLPO c-Fos. HSF extract also increased GABAAR α1 mRNA level. Our results suggest that HSF extract and saponarin are effective in maintaining sleep and may be used as a novel treatment for sleep disorder. Eventually, we hope to introduce HSF and saponarin as a clinical treatment for sleep disorders in humans.

Levels of trace blood elements associated with severe sleep disturbance in maintenance hemodialysis patients.

PURPOSE: Sleep disturbance is frequently observed in patients on maintenance hemodialysis (MHD), and this population usually presents imbalances in trace elements. We investigated the association between blood trace element levels and sleep quality in patients on MHD. METHODS: This cross-sectional and single-center study was performed in September 2019. Patients regularly undergoing hemodialysis for > 3 months at our center were recruited, and demographic, clinical, and laboratory parameters were recorded. The Pittsburgh Sleep Quality Index (PSQI) was applied to define sleep disturbance. Blood trace element (zinc, manganese, copper, selenium, and lead) levels were measured using an inductively coupled plasma mass spectrometer. RESULTS: In total, 121 patients on MHD (male/female = 68:53) were enrolled in the study (mean age 63.7 ± 13.9 years, median dialysis vintage 38.0 [20.0, 60.0] months). According to PSQI, 56 (46%) patients experienced severe sleep disturbance. These patients were characterized by older age, higher serum parathyroid hormone levels, and lower blood selenium levels (all P < 0.05). No significant differences in blood zinc, manganese, copper, and lead levels were observed between groups. Univariate binary logistic regression showed that lower blood selenium levels were associated with severe sleep disturbance (odds ratio = 0.976, 95% confidence interval: 0.954-0.999, P = 0.038). Multivariate analyses also confirmed the results after adjusting for confounding factors. CONCLUSION: Our study indicated an association between lower blood selenium levels and the occurrence of severe sleep disturbances in patients on MHD. However, a prospective study with a larger sample size and assessing the importance of selenium supplementation are needed to confirm the results.

Probiotics, Anticipation Stress, and the Acute Immune Response to Night Shift.

Introduction: Sleep disturbance and sleep disruption are associated with chronic, low grade inflammation and may underpin a range of chronic diseases in night shift workers. Through modulation of the intestinal microbiota, probiotic supplements may moderate the effects of sleep disruption on the immune system. The aim of this study was to examine 14 days of daily probiotic supplementation on the acute response of acute phase proteins and immune markers to sleep disruption associated with night shift work (Australia and New Zealand Clinical Trials Registry: 12617001552370). Methods: Individuals (mean age 41 ± 11 yrs; 74% female) performing routine night shift were randomly assigned to a probiotic group (1 × 1010 colony forming units (CFU) Lactobacillus acidophilus DDS-1 or 1 × 1010 CFU Bifidobacterium animalis subsp. lactis UABla-12) or placebo (n= 29 per group). Participants undertook a 14-day supplementation period that coincided with a period of no night shifts followed by two consecutive night shifts. Blood samples were collected prior to the start of supplementation (V1), prior to commencing the first night shift (V2), after the first night shift (V3) and after the second night shift (V4). Serum was assessed for markers of stress (cortisol), acute phase response (C reactive protein (CRP), erythrocyte sedimentation rate, pentraxin), adhesion markers (serum E-selectin, mucosal vascular addressin cell adhesion molecule 1 (MAdCAM-1), and serum cytokines (interleukin (IL)-1ra, IL-1ß, IL-6, tumor necrosis factor (TNF)-α, IL-10). Sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI) and a Fitbit activity tracker. Results: The groups were well balanced on key markers and the probiotic strains were well tolerated. The 14-day supplementation period that coincided with typical night-day sleep-wake cycles leading up to night shift (V1 to V2) was associated with significant changes in the placebo group in the concentration of serum cortisol (p = 0.01), pentraxin (p = 0.001), MAdCAM-1 (p = 0.001), and IL-1ra (p=0.03). In contrast, probiotic supplementation moderated changes in these serum markers from V1 to V2. No significant interaction effects (time by group) were observed for the serum markers prior to and after night shift work following probiotic supplementation due to the substantial changes in the serum markers that occurred during the normal sleep period from V1 to V2. Conclusions: Probiotics may moderate the effects of anticipatory stress on the immune system in the lead up to night shift.

Aerobic exercise modulates cytokine profile and sleep quality in elderly.

BACKGROUND: Sleep disturbance is a major problem for older adults which can be exacerbated by increased inflammation as aging is associated with increased circulating pro-inflammatory and lower anti-inflammatory cytokines. There is a need to develop alternative medicine techniques to help improve sleep quality in the elderly. OBJECTIVE: To investigate the effects of aerobic exercise training on the sleep quality and inflammatory cytokines in elderly subjects. MATERIAL AND METHODS: Forty previously sedentary elderly subjects participated in this study, their age ranged from 61- 67 years. All subjects were randomly assigned to supervised aerobic exercise intervention group (group A, n=25) or control group (group B, n=25). Polysomnographic recordings for sleep quality assessment, interleukin- 6 (IL-6), tumor necrosis factor- alpha (TNF-α) and interleukin-10 (IL-10) were measured before and after 6 months at the end of the study. RESULTS: There was a significant increase in total sleep duration, sleep efficiency and sleep onset latency in group(A) after 6 months of aerobic exercise training, while, wake time after sleep onset and rapid eye movement (REM) latency significantly reduced after 6 months of aerobic training compared with values obtained prior to aerobic exercise training. Also, the mean values of TNF- α and IL-6 decreased significantly and the mean value of IL-10 significantly increased in group (A) after the aerobic exercise training, however the results of the control group were not significant. Moreover, there were significant differences between both groups at the end of the study. CONCLUSION: Exercise training can be considered as a non-pharmacological modality for modifying sleep quality and inflammation among elderly.

The effect of uric acid on sleep quality after acute ischemic stroke.

Sleep disturbance is a common psychiatric complication after stroke. Oxidative stress has been an important pathophysiological mechanism of sleep disturbance. However, no study has explored the relationship between uric acid (UA) and post-stroke sleep quality. This prospective study included 191 patients who were followed up for two months after acute ischemic stroke. Serum UA levels were measured at admission and divided into 3 tertiles (≤251 µmol/L, 252-326 µmol/L, ≥327 µmol/L). Patients in the 3rd tertile of UA levels had a lower incidence of poor sleep quality than those belonging to 2nd or 1st tertile, respectively (9.7% vs. 27.7% vs. 35.9%; P = 0.002). Furthermore, high UA levels (≥327 µmol/L) were independently associated with low risk of poor sleep quality (OR = 0.129, 95%CI = 0.031-0.528, P = 0.004) after adjusting for demographics, cardiovascular risk factors, stroke severity, functional outcome and depressive symptoms. High modified Rankin Scale score and depressive symptoms were associated with increased risk of poor sleep quality after stroke (OR = 1.836, 95%CI = 1.035-3.354, P = 0.038) and (OR = 5.082, 95%CI = 1.709-15.115, P = 0.003). In conclusion, high UA levels may reduce the risk of poor sleep quality after acute ischemic stroke. Further randomized controlled trials are necessary in examining whether appropriate UA supplement could provide a potential prevention or therapeutic target for sleep disturbance after stroke.

Low omega-3 index and polyunsaturated fatty acid status in patients with chronic fatigue syndrome/myalgic encephalomyelitis.

BACKGROUND: Several studies have suggested that low levels of omega-3 fatty acids (n-3 PUFAs) including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are associated with cardiovascular risk, major depression, sleep problems, inflammation and other health-related issues. So far, however, erythrocyte PUFA status in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) has not been established. This study aimed to determine whether n-3 PUFA content and omega-3 index are associated with measures in CFS/ME patients. PATIENTS AND METHODS: PUFA levels and omega-3 index were measured in 31 Spanish CFS/ME patients using the HS-Omega-3 Index method. Demographic and clinical characteristics and self-reported outcome measures were also recorded. RESULTS: A low mean omega-3 index (5.75%) was observed in 92.6% of the sample. Omega-3 index was inversely correlated with the AA/EPA ratio (p = 0.00002) and the BMI (p = 0.0106). In contrast, the AA/EPA ratio was positively associated with the BMI (p = 0.0038). No association for FIS-40 and PSQI measures was found (p > 0.05). CONCLUSION: The low omega-3 index found in our CFS/ME patients may indicate increased risks for cardiovascular health, which should be further investigated. A low omega-3 index also suggests a pro-inflammatory state in these patients. Attempts should be made to increase the omega-3 index in CFS/ME patients, based on intervention trials assessing a potential therapeutic value.

Habitual light exposure relative to circadian timing in delayed sleep-wake phase disorder.

Study Objectives: To compare melatonin timing, a well-validated marker for endogenous circadian phase, and habitual light-exposure patterns in adults with delayed sleep-wake phase disorder (DSWPD) and intermediate chronotype controls. Methods: Twelve individuals with DSWPD (five females, mean age: 31.1) and 12 age-matched controls (six females, mean age: 33.6) underwent a minimum of 7 days of light and activity monitoring followed by an inpatient hospital stay, where blood was taken to assess melatonin timing (calculated as dim light melatonin onset-DLMO). Habitual light-exposure patterns were then compared with a human phase-response curve (PRC) to light. Results: Relative to clock time, individuals with DSWPD had a later light-exposure pattern compared with controls, but their light-exposure pattern was earlier relative to DLMO. According to the human PRC to light, individuals with DSWPD had less daily advancing light exposure compared with controls. The primary difference was seen in the late portion of the advancing window, in which individuals with DSWPD were exposed to fewer pulses of light of equivalent duration and intensity compared with controls. Conclusions: Diminished advancing light exposure may play a role in the development and perpetuation of delayed sleep-wake timing in individuals with DSWPD. Enhancing light exposure during the later portion of the advancing window represents an innovative and complementary strategy that has the potential to improve the effectiveness of bright light therapy in DSWPD.

Study protocol and rationale for a prospective, randomized, double-blind, placebo-controlled study to evaluate the effects of Ashwagandha (Withania somnifera) extract on nonrestorative sleep.

Nonrestorative sleep (NRS) is one of the cardinal symptoms of insomnia and can occur independent of other components of insomnia. Among the sleep disturbances, NRS has been little studied in the general population, even though this symptom plays an important role in several medical conditions associated with chronic inflammation such as heart disease, fibromyalgia, and chronic fatigue syndrome, as well as various sleep disorders. There is paucity in the literature about effective treatments for NRS. Ashwagandha (Withania somnifera) has been demonstrated to reduce anxiety and stress, allowing the body to settle down and prepare for sleep. This study will be a double-blind, randomized, placebo-controlled interventional study in NRS population.The NRS participants are identified using Restorative Sleep Questionnaire-weekly version (RSQ-W) questionnaire. Actigraphy and polysomnography are used for the objective assessment of sleep. The other assessments used are Hamilton Anxiety Depression Scale (HADS), World Health Organization Quality of Life (WHOQOL) scales, and C-reactive protein. Routine blood and urine analyses will be conducted to assess the safety of treatment. Duration of study for each participant will be 50 days with "day one" for screening followed by randomization for the treatment. The duration for medicine/placebo intake shall be 42 days.Primary outcome will be to evaluate effect of daily supplement of ashwagandha extract compared with placebo in subjects with NRS at 6 weeks from baseline, as assessed by the total score of RSQ-W. CTRI REGISTRATION NUMBER: CTRI/2017/02/007801.

The effect of vitamin D supplement on the score and quality of sleep in 20-50 year-old people with sleep disorders compared with control group.

OBJECTIVES: Sleep quality may be directly related with vitamin D serum level. Some studies found that people with lower vitamin D serum level experienced a lower sleep quality. Consequently, this study aimed at determining the effect of vitamin D supplements on sleep score and quality in 20-50 year-old people with sleep disorders. METHODS: This double blind, clinical trial was performed in November 2015-February 2016 on 89 people with sleep disorders based on Petersburg's Sleep Index. Patient samples were divided randomly into two groups: intervention and placebo. At the end of the study, the data on 89 subjects (44 in intervention group and 45 people in placebo group) were examined. Intervention group received a 50 000-unit vitamin D supplement, one in a fortnight for 8 weeks. Meanwhile, placebo group received placebo. Before and after intervention, Petersburg's Sleep Quality Questionnaire, International Physical Activity Questionnaire, general information questionnaire, sun exposure, vitamin D serum level and 3-day food record questionnaire were assessed and recorded for all participants. To analyze data, t-test, chi square, ANCOVA, U-Mann-Whitney and Wilcoxon statistical tests were used. FINDINGS: Based on the results of the present study, at the end of the study sleep score (PSQI) reduced significantly in vitamin recipients as compared with placebo recipients (P < 0.05). This difference was significant even after modifying confounding variables (P < 0.05). CONCLUSION: This study shows that the use of vitamin D supplement improves sleep quality, reduces sleep latency, raises sleep duration and improves subjective sleep quality in people of 20-50 year-old with sleep disorder.

Sleep disorders of acute thalamic stroke and its influence on plasma IL-17.

The aim of this study was to investigate the relationship between sleep disorders in acute thalamus stroke patients and plasma IL-17 levels and the mechanism through which inflammatory reactions develop in stroke. The study included two groups of patients: an experimental group consisting of 30 patients with thalamus stroke who received treatment at the Affiliated Hong Qi Hospital of Mu Dan Jiang Medical University during October 2015 to October 2016 and a control group consisting of 15 healthy volunteers. All the subjects included in the study were biochemically monitored for blood glucose, blood fats and IL-17 plasma levels. The sleep quality of all the subjects included in the study was evaluated [Epwort, Pittsburgh Sleep Quality Index (PSQI)] with 8-hour Polysonmography (PSG) monitoring. The experimental group was divided into 3 subgroups according to the part of the brain affected by stroke: anterior thalamus nucleus group, lateral thalamus nucleus group and medial thalamus nucleus group. The differences were analyzed between the experimental group and the control group in sleep quality scores, sleep structural changes, and plasma IL-17 levels. The differences in sleep structural scores were also analyzed according to different parts of the brain affected by stroke. The experimental group had a higher PSQI score compared with the control group, but this difference had no statistical significance (p>0.05). Compared with the control group, the N1 phase of the experimental group was longer while the N2 and N3 phases were shorter (p<0.05). There were no differences in sleep structure between the three regions of the brain affected by stroke (anterior thalamus nucleus group, lateral thalamus nucleus group and medial thalamus nucleus group) (p > 0.05). The plasma levels of IL-17 in the experimental group was higher compared to the control group (p<0.05). In the experimental group, the patients with hypersomnia had higher IL-17 levels than patients without hypersomnia (p<0.01). We can conclude that PSG can be used as an electrophysiology index for early detection of sleep disorders in thalamus stroke patients. Sleep disorders in patients with thalamus stroke persist a long time after the incident, therefore monitoring their sleep structure may become an important index to predict the prognosis of the disease. The increased level of IL-17 level in the experimental group shows its implication in appearance of sleep disorders of acute thalamus stroke through inflammatory mechanism.

[Influence chronopharmacology therapy methionine (melaxen) on the dynamics of sleep disturbance, cognitive and emotional disorders, brain-derived neurotrophic factor (BDNF) in patients with cerebral stroke in the early and late recovery periods]. / Vliianie khronofarmakologicheskoi terapii melatoninom (melaksen) na dinamiku narushenii sna, kognitivnykh i émotsional'nykh rasstroistv, neirotroficheskogo faktora mozga u patsientov v vosstanovitel'nom periode insul'ta.

AIM: To study the efficacy of melaxen on the dynamics of sleep disturbance, cognitive and emotional disorders, BDNF and the level of secretion of melatonin (6-SOMT) in patients with stroke in the early and late recovery phase. MATERIAL AND METHODS: One hundred and ten patients in the rehabilitation period of stroke (mean age of 58.4±6.4 years), including 60 patients in the early recovery phase (group 1) and 50 patients in the late phase (group 2), were studied. Patients received melaxen in dose of 3 mg/day for 3 months along with standard treatment. The efficacy of therapy was assessed by the dynamics of sleep disorders, emotional status, dynamics of serum BDNF levels, 6-SOMT concentration in the urine. RESULTS AND CONCLUSION: The study has demonstrated the high efficacy of melaxen in the rehabilitation of patients in early and late recovery phase of stroke. The drug significantly increased the BDNF level that correlated with improved sleep, emotional status, quality of life of patients.

Physiological melatonin levels in healthy older people: A systematic review.

OBJECTIVE: Melatonin plays a major role in maintaining circadian rhythm. Previous studies showed that its secretion pattern and levels could be disturbed in persons with dementia, psychiatric disorders, sleep disorders or with cancer. Also ageing is a factor that could alter melatonin levels, although previous research provides contradicting results. As melatonin supplementation is increasingly applied in older persons as sleep medication, it is important to know if melatonin levels decrease in healthy ageing and/or secretion patterns change. The objective of this study is to determine physiological levels and secretion patterns of melatonin in healthy older people. METHODS: We performed a systematic review and searched PubMed and Embase for studies published between January 1st 1980 and October 5th 2015 that measured melatonin in healthy persons aged ≥65years. RESULTS: Nineteen studies were retrieved. The number of participants ranged from 5 to 60 per study. Melatonin was mostly measured by radioimmunoassay (RIA) and the number of measurements per 24hours varied from 1 to 96. Sixteen studies showed a secretion pattern with a clear peak concentration, mostly at 0200h or 0300h. Maximum concentrations varied greatly from 11.2 to 91.3pgml(-1). Maximum melatonin level in studies with participants mean aged 65-70years was 49.3pgml(-1) and in studies with participants mean aged ≥75years 27.8pgml(-1), p-value <0.001. CONCLUSION: Total melatonin production in 24hours seems not to change in healthy ageing, but the maximal nocturnal peak concentration of melatonin might decline. It is important to take this into account when prescribing melatonin supplementation to older people.

Melatonin Supplementation for Children With Atopic Dermatitis and Sleep Disturbance: A Randomized Clinical Trial.

IMPORTANCE: Sleep disturbance is common in children with atopic dermatitis (AD), but effective clinical management for this problem is lacking. Reduced levels of nocturnal melatonin were found to be associated with sleep disturbance and increased disease severity in children with AD. Melatonin also has sleep-inducing and anti-inflammatory properties and therefore might be useful for the management of AD. OBJECTIVE: To evaluate the effectiveness of melatonin supplementation for improving the sleep disturbance and severity of disease in children with AD. DESIGN, SETTING, AND PARTICIPANTS: This randomized clinical trial used a double-blind, placebo-controlled crossover design to study 73 children and adolescents aged 1 to 18 years with physician-diagnosed AD involving at least 5% of the total body surface area. The study was conducted at the pediatric department of a large tertiary care hospital in Taiwan from August 1, 2012, through January 31, 2013. Forty-eight children were randomized 1:1 to melatonin or placebo treatment, and 38 of these (79%) completed the cross-over period of the trial. Final follow-up occurred on April 13, 2013, and data were analyzed from January 27 to April 25, 2014. Analyses were based on intention to treat. INTERVENTIONS: Melatonin, 3 mg/d, or placebo for 4 weeks followed by a 2-week washout period and then crossover to the alternate treatment for 4 weeks. MAIN OUTCOMES AND MEASURES: The primary outcome was AD severity evaluated using the Scoring Atopic Dermatitis (SCORAD) index, with scores ranging from 0 to 103 and greater scores indicating worse symptoms. Secondary outcomes included sleep variables measured by actigraphy, subjective change in sleep and dermatitis, sleep variables measured by polysomnography, nocturnal urinary levels of 6-sulfatoxymelatonin, and serum IgE levels. RESULTS: After melatonin treatment among the 48 children included in the study, the SCORAD index decreased by 9.1 compared with after placebo (95% CI, -13.7 to -4.6; P < .001), from a mean (SD) of 49.1 (24.3) to 40.2 (20.9). Moreover, the sleep-onset latency shortened by 21.4 minutes after melatonin treatment compared with after placebo (95% CI, -38.6 to -4.2; P = .02). The improvement in the SCORAD index did not correlate significantly with the change in sleep-onset latency (r = -0.04; P = .85). No patient withdrew owing to adverse events, and no adverse event was reported throughout the study. CONCLUSIONS AND RELEVANCE: Melatonin supplementation is a safe and effective way to improve the sleep-onset latency and disease severity in children with AD. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01638234.

Chronic treatment with a tryptophan-rich protein hydrolysate improves emotional processing, mental energy levels and reaction time in middle-aged women.

Common pharmacological treatments of mood disorders aim to modulate serotonergic neurotransmission and enhance serotonin levels in the brain. Brain serotonin levels are dependent on the availability of its food-derived precursor essential amino acid tryptophan (Trp). We tested the hypothesis that delivery of Trp via food may serve as an alternative treatment, and examined the effects of a Trp-rich, bioavailable dietary supplement from egg protein hydrolysate on cognitive and emotional functions, mood state, and sleep quality. In a randomised, placebo-controlled, parallel trial, fifty-nine mentally and physically healthy women aged 45-65 years received placebo (n 30) or the supplement (n 29) (both as 0.5 g twice per d) for 19 d. Emotional processing was significantly changed by supplementation, exhibiting a shift in bias away from negative stimuli. The results for the Affective Go/No-Go Task exhibited a slowing of responses to negative words, suggesting reduced attention to negative emotional stimuli. The results for the Facial Emotional Expression Rating Task also supported a shift away from attention to negative emotions and a bias towards happiness. An increase in arousal-like symptoms, labelled 'high energy', shorter reaction times and a slight benefit to sustained attention were observed in the treated subjects. Finally, when the supplement was taken 60-90 min before bedtime, a feeling of happiness before going to bed was consistently reported. In summary, daily consumption of a low-dose supplement containing bioavailable Trp may have beneficial effects on emotional and cognitive functions.

Sleep disruption in tetraplegia: a randomised, double-blind, placebo-controlled crossover trial of 3 mg melatonin.

STUDY DESIGN: Randomised, double-blind, placebo-controlled crossover trial of melatonin supplementation to people with complete tetraplegia. OBJECTIVES: To investigate the effect that 3 mg melatonin supplementation has on objective and subjective sleep, quality of life and mood of people living with complete tetraplegia. SETTING: Austin Hospital Sleep Laboratory and participants' homes, Melbourne, Victoria, Australia. METHODS: Two week run-in followed by 3 week nightly administration of 3 mg melatonin or placebo, 2-week washout and further 3 week administration of the opposite treatment. Four testing sessions were conducted; the last nights of the run-in, treatment and washout periods. Testing sessions involved recording full polysomnography, completing a questionnaire battery and collecting urine and blood samples. The questionnaires assessed mood, sleep symptoms and health-related quality of life, and the urine and plasma samples assayed 6-sulphatoxymelatonin (aMT6s) and melatonin levels, respectively. A sleep diary was completed throughout the study. RESULTS: Eight participants (mean (s.d.): age 49.5 years (16), postinjury 16.9 years (7.1)) were recruited in which seven concluded the protocol. Endogenous-circulating melatonin was significantly higher (P < or = 0.01) following melatonin (urine: 152.94 µg h(-1) (74.51), plasma: 43,554.57 pM (33,527.11)) than placebo (urine: 0.86 µg h(-1) (0.40), plasma: 152.06 pM (190.55)). Subjective sleep improved significantly following melatonin specifically for duration of sleep per night and psychological wellbeing. Objective sleep showed a significant increase in light sleep with melatonin, with all other sleep parameters being unchanged. CONCLUSION: These results suggest that increasing melatonin in people with complete tetraplegia is beneficial, especially for subjective sleep. Investigation of the pharmacokinetics of melatonin metabolism in this population is warranted. SPONSORSHIP: This project is proudly supported by the Transport Accident Commission.

Vitamin D levels and menopause-related symptoms.

OBJECTIVE: This study aims to determine whether vitamin D levels are associated with menopause-related symptoms in older women. METHODS: A randomly selected subset of 1,407 women, among 26,104 potentially eligible participants of the Women's Health Initiative Calcium and Vitamin D trial of postmenopausal women aged 51 to 80 years, had 25-hydroxyvitamin D [25(OH)D] levels measured at the Women's Health Initiative Calcium and Vitamin D trial baseline visit. Information about menopause-related symptoms at baseline was obtained by questionnaire and included overall number of symptoms and composite measures of sleep disturbance, emotional well-being, and energy/fatigue, as well as individual symptoms. After exclusions for missing data, 530 women (mean [SD] age, 66.2 [6.8] y) were included in these analyses. RESULTS: Borderline significant associations between 25(OH)D levels and total number of menopausal symptoms were observed (with P values ranging from 0.05 to 0.06 for fully adjusted models); however, the effect was clinically insignificant and disappeared with correction for multiple testing. No associations between 25(OH)D levels and composite measures of sleep disturbance, emotional well-being, or energy/fatigue were observed (P's > 0.10 for fully adjusted models). CONCLUSIONS: There is no evidence for a clinically important association between serum 25(OH)D levels and menopause-related symptoms in postmenopausal women.

Fatty acids and sleep in UK children: subjective and pilot objective sleep results from the DOLAB study--a randomized controlled trial.

Sleep problems in children are associated with poor health, behavioural and cognitive problems, as are deficiencies of long-chain omega-3 fatty acids such as docosahexaenoic acid. Theory and some evidence support a role for these fatty acids in sleep regulation, but this issue has received little formal investigation. We examined associations between blood fatty acid concentrations (from fingerstick blood samples) and subjective sleep (using an age-standardized parent questionnaire) in a large epidemiological sample of healthy children aged 7-9 years (n = 395) from mainstream UK schools. In a randomized controlled trial, we then explored whether 16-week supplementation (600 mg day(-1) ) with algal docosahexaenoic acid versus placebo might improve sleep in a subset of those children (n = 362) who were underperforming in reading. In a randomly selected subsample (n = 43), sleep was also assessed objectively via actigraphy. In 40% of the epidemiological sample, Child Sleep Habits Questionnaire scores indicated clinical-level sleep problems. Furthermore, poorer total sleep disturbance scores were associated weakly but significantly with lower blood docosahexaenoic acid (std coeff. -0.105*) and a lower docosahexaenoic acid : arachidonic acid ratio (std coeff. -0.119**). The treatment trial showed no significant effects on subjective sleep measures. However, in the small actigraphy subsample, docosahexaenoic acid supplementation led on average to seven fewer wake episodes and 58 min more sleep per night. Cautiously, we conclude that higher blood levels of docosahexaenoic acid may relate to better child sleep, as rated by parents. Exploratory pilot objective evidence from actigraphy suggests that docosahexaenoic acid supplementation may improve children's sleep, but further investigations are needed.

[Depression as chronobiological illness]. / A depresszió mint kronobiológiai betegség.

Chronobiological problems are always present as aetiological or pathoplastic conditions almost in all psychiatric disorders and considered as the greatest contributors to the mood and sleep disorders associated problems. The present review summarise the recent advances in the chronobiology research from the point of the clinician with particular emphasis on the psychobiology and pharmacotherapy of the depression. Human behaviour builds up from different length of circadian, ultradian and seasonal rhytms, strictly controlled by a hierarchical organisation of sub-cellullar, cellular, neuro-humoral and neuro-immunological clock systems. These internal clock systems are orchestrated at molecular level by certain clock genes and on the other hand--at neuro-humoral level--by the effect of the sleep hormone, melatonine, produced by the neurons of the suprachiasmatic nucleus (SCN). Beside the biological factors, social interactions are also considered as important regulators of the biological clock systems. The pacemaker centers of the SCN receive efferents from the serotoninergic raphe nuclei in order to regulate stress responses and neuroimmunological functions. The direction and the level of the chronobiological desynchronisation could be totally divergent in the case of the different affective disorders. Different chronobiological interventions are required therefore in the case of the advanced and delayed sleep disorders. Sleeping disorders are considered as the most recognised signs of the chronobiological desynchronisation in depression, but these symptoms are only the tip of the iceberg, since other chronobiological symptoms could be present due to the hidden physiological abnormalities. The serum melatonine profile is considered to be characteristic to age, gender and certain neuropsychiatric disorders. The natural and synthetic agonist of the melatonine receptors could be used as chronobiotics. The recently marketed agomelatine with a highly selective receptor binding profile (MT1 and MT2 agonism and 5HT2C antagonism) targets the desynchronised circadian rhytm in affective disorders and it has mainly antidepressive effect. Among the non-pharmacological chronobiological interventions, the different forms of the sleep deprivation, light and social rhytm therapies could offer alternative treatment options for the clinician.

Sleep disturbances and serum ferritin levels in children with attention-deficit/hyperactivity disorder.

BACKGROUND: A subset of children with attention-deficit/hyperactivity disorder (ADHD) may present with impairing sleep disturbances. While preliminary evidence suggests that iron deficiency might be involved into the pathophysiology of daytime ADHD symptoms, no research has been conducted to explore the relationship between iron deficiency and sleep disturbances in patients with ADHD. The aim of this study was to assess the association between serum ferritin levels and parent reports of sleep disturbances in a sample of children with ADHD. SUBJECTS: Sixty-eight consecutively referred children (6-14 years) with ADHD diagnosed according to DSM-IV criteria using the semi-structured interview Kiddie-SADS-PL. MEASURES: parents filled out the Sleep Disturbance Scale for Children (SDSC) and the Conners Parent Rating Scale (CPRS). Serum ferritin levels were determined using the Tinaquant method. RESULTS: Compared to children with serum ferritin levels >or=45 microg/l, those with serum ferritin levels <45 microg/l had significantly higher scores on the SDSC subscale "Sleep wake transition disorders" (SWTD) (P = 0.042), which includes items on abnormal movements in sleep, as well as significantly higher scores on the CPRS-ADHD index (P = 0.034). The mean scores on the other SDSC subscales did not significantly differ between children with serum ferritin >or=45 and <45 microg/l. Serum ferritin levels were inversely correlated to SWTD scores (P = 0.043). CONCLUSION: Serum ferritin levels <45 microg/l might indicate a risk for sleep wake transition disorders, including abnormal sleep movements, in children with ADHD. Our results based on questionnaires set the basis for further actigraphic and polysomnographic studies on nighttime activity and iron deficiency in ADHD. Research in this field may suggest future trials of iron supplementation (possibly in association with ADHD medications) for abnormal sleep motor activity in children with ADHD.