Association of weekday-to-weekend sleep differences and stress response among a Japanese working population: a cross-sectional study.

OBJECTIVES: To investigate the relationship between differences in weekday-to-weekend sleep habits and stress responses in a working population. METHODS: This cross-sectional study used data from university workers on sleep habits, differences in sleep duration between weekdays and weekends, and each midpoint of the sleep phase on weekdays and weekends. Social jetlag was defined as the difference in the midpoint of the sleep phase between weekdays and weekends. In addition, the Brief Job Stress Questionnaire assessed stress responses and stress-related factors. To examine sleep-related factors affecting stress responses, regression analysis was performed with adjustments for age, sex, and stress-related factors. RESULTS: Analyzed were 2,739 participants. Sleep duration differences obtained by subtracting sleep duration on weekdays from that on weekends, social jetlag, and weekday sleep duration were significantly associated with an increased risk of stress responses in a univariate linear regression model. Adjusting for age, sex, job stressors, and stressor buffering factors did not change this trend. However, when additionally adjusting for all sleep parameters, only sleep duration differences and weekday sleep duration were significantly associated with stress responses (ß 0.67 [95% CI 0.24, 1.10], p = 0.002), (-0.66 [-1.20, -0.13], p = 0.015). CONCLUSIONS: This study provided further evidence that weekday sleep duration and weekday-to-weekend sleep duration differences were independently associated with stress responses even when considering stress-related factors. However, social jetlag was not clearly associated with stress responses. Our findings highlighted the necessity of securing sufficient sleep for stress management and mental health promotion in a working population.

Decline in the severity or the incidence of schizophrenia in Japan: A survey of university students.

Clinical manifestations of schizophrenia are believed to be becoming less severe in Japan, but little evidence supports this theory. We investigated the percentages of undergraduate students attending national universities in Japan who required temporary leave and who dropped out because of schizophrenia in the academic years 1986-1987, 1994-1995, and 2013-2014. The percentages of students who required temporary leave and those who dropped out because of schizophrenia significantly decreased over time. The severity of clinical manifestations of schizophrenia may have decreased, enabling more students with schizophrenia to continue their study, or the incidence of schizophrenia might have declined.

Sense of coherence, health problems, and presenteeism in Japanese university students.

AIM: Sense of coherence (SOC) is thought to be a major determinant in maintaining health. SOC gained attention recently in the fields of psychiatry after it was reported to be associated with a lowered risk of various health problems. However, the effect of SOC as a buffer against performance impairment caused by health problems is not well known. Thus, we aimed to examine the relationships among health problem, the degree of presenteeism (performance loss due to health problems), and SOC in adolescents. METHODS: Participants were 2824 university students (1855 males, mean age; 18.35±0.84 years). SOC and self-reported health problems were assessed using an SOC scale (29 items) and the presenteeism scale for students, respectively. RESULTS: SOC scores differed between students with and without health problems (t(2822)=5.75, P<0.001). The effect size (Cohen's d) was 0.22 for this difference. In a multiple logistic regression analysis, male gender (odds ratio [OR]=0.62; 95% confidence interval [CI]=0.53-0.73), moderate SOC (within ±1 SD; OR=0.59; 95% CI=0.47-0.72), and high SOC (>1 SD; OR=0.43; 95% CI=0.33-0.58) were independently associated with a lower frequently of health problems. In addition, SOC showed a significant inverse correlation with presenteeism (r=-0.27, P<0.001). CONCLUSION: These results suggest that application of the concept of SOC might aid in the prevention of health problems among university students. Students with a strong SOC might be less prone to a decline in performance when health problems arise.

Efficacy and tolerability of ramelteon in a double-blind, placebo-controlled, crossover study in Japanese patients with chronic primary insomnia.

The aim of this study was to evaluate the efficacy and safety of ramelteon 4, 8, 16 or 32 mg and placebo in Japanese patients with chronic insomnia using a randomized, double-blind, five-period crossover design. A total of 65 Japanese patients with chronic primary insomnia received ramelteon or placebo for two nights each in sleep laboratories. Changes in sleep parameters were assessed objectively by polysomnography and subjectively by postsleep questionnaires. Safety and tolerability was evaluated by assessment of the occurrence of adverse events, next-day residual effects and laboratory and ECG investigations. Ramelteon 8 and 32 mg significantly shortened the mean latency to persistent sleep in comparison with placebo, and there was a statistically significant trend for linear dose-response for this sleep parameter. Overall changes in sleep architecture were modest (<3% changes vs placebo), with increases in stage 1 and decreases in stage 3/4. Ramelteon was well tolerated, the most common adverse effect being somnolence, which was similar to placebo at doses up to 8 mg, but increased with higher doses. Next-day residual effects occurred no more frequently with ramelteon at any dose than with placebo. When compared with sleep latency data from a similarly-designed US study, there was no evidence of any ethnic differences in the efficacy of ramelteon between Japanese and US patients. Overall, ramelteon 8 mg showed the most favorable balance between sleep-promoting effects and tolerability. The unique efficacy profile of ramelteon, promoting sleep initiation without affecting other sleep parameters, may be due to its circadian shifting effect.

Presenteeism in college students: reliability and validity of the Presenteeism Scale for Students.

OBJECTIVE: Presenteeism is the impaired work performance due to health problems. We aimed to develop a Presenteeism Scale for Students (PSS), and to reveal the existence of presenteeism among students. METHODS: Students (n = 5,701) in 4 national universities in Japan were recruited via the school-based health examination. Moreover, 122 students participated in a 2-week interval test-retest to examine the reliability and criterion-related validity of the PSS. RESULTS: Of the students, 59.2% indicated some health problems. Allergy was most prevalent health problems, affecting 35.7% of the whole students. Students with emotional problems had higher degree of presenteeism than those with the other problems. The Cronbach's α of the work impairment score of the PSS was 0.90. The Spearman's coefficient for the test-retest score was 0.80 (P < 0.001). Regarding criterion-related validity, Spearman's coefficient between the work impairment score of the PSS and summary score of the SF-36 was -0.60 (P < 0.001). CONCLUSIONS: These findings suggest that the PSS can be expected to be useful for assessment of students with presenteeism. Furthermore, we found that the majority of students have some health problems, and proposed that the issue of presenteeism on campus should be addressed.

Anxiety, neuroticism and oxidative stress: cross-sectional study in non-smoking college students.

AIMS: Oxidative stress has gained attention recently in psychiatric medicine and has been reported to be associated with various diseases. However, the psychosocial factors involved in oxidative stress are still not well understood. Thus, the aim of this study was to examine whether anxiety levels and neuroticism were associated with serum oxidative and anti-oxidative status in healthy college students. METHODS: Participants in this cross-sectional study were 54 non-smoking college students. Their serum oxidative status was determined by reactive oxygen metabolites (ROM) and the biological anti-oxidant potential. Anxiety levels and neuroticism were assessed using the State-Trait Anxiety Inventory and the NEO Five-Factor Inventory, respectively. RESULTS: Correlation analysis showed an association of increased ROM concentration with elevated anxiety levels (State, rho = 0.39, P = 0.046; Trait, rho = 0.44, P = 0.024) and the personality trait of neuroticism (rho = 0.47, P = 0.016) in female students. However, the ROM concentration in male students was not associated with the anxiety level or any personality trait. CONCLUSION: Although these findings suggest that neurotic and anxious female students tend to be exposed to oxidative stress, these linkages should be confirmed by multivariate analysis in future research.

Urgency is an independent factor for sleep disturbance in men with obstructive sleep apnea.

OBJECTIVES: The relationship between overactive bladder (OAB) symptoms, other than nocturia, and sleep, has not been fully evaluated, although a close relationship between nocturia and sleep disturbance has been reported. In the present study, we evaluated the relationship between OAB symptoms and several polysomnography (PSG) parameters in middle-age men with sleep disturbance, especially to clarify whether urgency as the hallmark symptom of an OAB is independently associated with sleep quality. METHODS: A total of 32 men >40 years of age (mean age 58.0 ± 12.6), who had been diagnosed with obstructive sleep apnea syndrome by PSG, were included in the present study. Their OAB symptoms were evaluated using the OAB symptom score (OABSS) before PSG. The relationship between the OABSS and several parameters, such as sleeping time, sleeping efficiency, sleep latency, percentage of rapid eye movement during sleeping time, and apnea/hypopnea index obtained from PSG, was evaluated. RESULTS: Multivariate analysis showed that only sleeping efficiency was an influencing factor on the total OABSS. Of the 4 subscores of OABSS, including frequency, nocturia, urgency, and urgency incontinence, multivariate analysis showed that the subscores of nocturia and urgency were independent influencing factors on sleeping efficiency. Nocturia correlated negatively with sleeping efficiency (Pearson's correlation 0.533, P <.01), and urgency also correlated negatively with sleeping efficiency (Pearson's correlation 0.492, P <.01). CONCLUSIONS: We found that urgency and nocturia were factors that independently affected sleep or were affected by sleep quality, although only the association of nocturia with sleep disturbance has been the focus of previous studies.

Do depressive symptoms correlate with oxidative stress in a sample of healthy college students?

Background and Objectives: Major depression and sub-threshold depressive symptoms are associated with health crisis. Oxidative stress may be a mechanism for major depression. In the present study, we examined the relationship between the degree of depressive symptoms and oxidative status using a reliable and inexpensive method that evaluates endogenous hydroperoxides. Methods: We conducted a cross-sectional study in 54 non-smoking college students and measured serum reactive oxygen metabolites (ROMs) and the biological antioxidant potential (BAP) as an index of oxidative status. Depressive symptoms were assessed by the Beck Depression Inventory (BDI). Results: The concentrations of ROMs did not differ between the lower BDI group (BDI < 14) and the higher BDI group (BDI > 14) (282.7 - 59.84 U.CARR vs 307.7 - 67.51 U.CARR, z = -1.19, P = 0.239). We did find a significant relationship between ROM concentration values and higher BDI scores (rho = 0.30, P = 0.042). BAP levels in the higher BDI group were not significantly greater than those in the lower BDI group (z = -0.108, P = 0.287). There was no significant correlation between BAP and depressive symptoms (rho = 0.22, P = 0.140). Moreover, we conducted a multiple regression analysis to control for gender difference and difference in sleep perception of the previous night between the two BDI groups. However, depressive symptoms were not significantly predicted by ROM concentrations (b = 0.28, P = 0.076). Conclusions: While results of the present study demonstrated a slight correlation between depressive symptoms and oxidative stress, this linkage could not be confirmed after controlling for significant confounding factors. This result should be verified in a larger sample (AU)

Abdominal obesity exhibits distinct effect on inflammatory and anti-inflammatory proteins in apparently healthy Japanese men.

BACKGROUND: Since visceral fat tissue is known to release various inflammatory and anti-inflammatory cytokines, abdominal obesity may play a key role in the inflammation associated with metabolic syndrome (MetS). However, few studies have determined precise relationships of abdominal obesity with inflammatory markers in MetS. To clarify the importance of abdominal obesity in sub-clinical inflammation, we examined the changes of inflammatory markers in clustering of MetS components with or without abdominal obesity. METHODS: Subjects consisted of 326 apparently healthy Japanese men (age: 30 to 59 years) who underwent health examination in the Osaka University Health Care Center. MetS components were assessed and serum levels of high sensitive C-reactive protein (hs-CRP), interleukin (IL)-6 and adiponectin were examined in all subjects. RESULTS: Subjects with abdominal obesity (waist circumference > or = 85 cm) showed higher serum hs-CRP and IL-6 levels and a lower adiponectin level than those without abdominal obesity. Serum levels of hs-CRP and IL-6 significantly increased in association with clustering of MetS components in the subjects with abdominal obesity, but not in those without abdominal obesity. On the other hand, serum adiponectin level exhibited a little change with clustering of MetS components in the subjects with abdominal obesity. Significant negative correlation between adiponectin and hs-CRP was observed in the subjects with abdominal obesity, however this correlation was not detected in obese subjects defined by body mass index > or = 25. CONCLUSION: Inflammatory status is not exaggerated by clustering of MetS components in the subjects without abdominal obesity. Abdominal obesity may exhibit distinct effect on inflammatory and anti-inflammatory proteins and modulate inflammatory network in MetS.

Effects of IL-6, adiponectin, CRP and metabolic syndrome on subclinical atherosclerosis.

BACKGROUND: Inflammation has been implicated in the pathogenesis of cardiovascular disease. Since there have been few studies elucidating gender-specific effect of inflammation and metabolic syndrome (MetS) on subclinical atherosclerosis, we evaluated the relative contribution of these factors in healthy subjects. METHODS: MetS components, carotid intima-media thickness (IMT) and pulse wave velocity (PWV) were evaluated in apparently healthy 714 men and 364 women (40-59 y). Serum levels of high sensitive C-reactive protein (hs-CRP), interleukin-6 (IL-6) and adiponectin were also examined. RESULTS: Increase in number of clustering MetS components was more clearly associated with worsening of IMT and PWV in women than in men. Serum IL-6 level was positively correlated with IMT and PWV, and adiponectin level was negatively correlated with IMT in men but not in women. The subjects either with a "high" IL-6 or hs-CRP, or a "low" adiponectin were associated with increase in IMT in the presence of MetS, though there was no significant effect of MetS in those with low inflammation. CONCLUSIONS: While IL-6 and adiponectin are the important risk factors for early arterial alterations in men, components of MetS present profound effects on subclinical atherosclerosis in women rather than in men.

Interleukin-10 associates with adiponectin predominantly in subjects with metabolic syndrome.

BACKGROUND: Inflammation and the metabolic syndrome (MetS) are important risk factors in cardiovascular disease. There is accumulating evidence that decreased adiponectin levels are associated with MetS. Recently, it was shown that adiponectin induces the expression of a potent anti-inflammatory cytokine, interleukin (IL)-10, in vitro. The aim of this study is to investigate the association of IL-10 levels with other pro-inflammatory and anti-inflammatory factors including adiponectin levels in vivo. METHODS AND RESULTS: MetS components were assessed in 117 drug-naïve middle-aged men. Serum levels of high-sensitive C-reactive protein (hs-CRP), IL-6, adiponectin, IL-10 and tumor necrosis factor-alpha (TNF-alpha) were measured in these subjects. A significant decrease in adiponectin (5.15+/-1.79 microg/ml vs 6.87+/-3.55 microg/ml, p<0.02) and an increase in IL-6 (1.50+/-1.50 pg/ml vs 1.06+/-0.78 pg/ml, p<0.05) levels were associated with MetS. The serum IL-10 level exhibited a significant positive correlation with IL-6, hs-CRP, and TNF-alpha levels, but not with adiponectin in healthy individuals. However, IL-10 exhibited a significant correlation with adiponectin, especially in the subjects with MetS. CONCLUSIONS: Serum IL-10 levels correlated with inflammatory proteins, but not with adiponectin. However, IL-10 positively associated with adiponectin especially in the subjects with MetS. IL-10 might be involved in the inflammatory network of MetS in relation to adiponectin.

[Sleep disturbance in chronic fatigue syndrome].

Attempts to elucidate the complex pathophysiology of chronic fatigue syndrome (CFS) must consider subjective and objective sleep. Several reports of CFS showed the high rate of sleep disturbance such as insomnia, hypersomnia, circadian rhythm sleep disorder, sleep apnea/hypopnea syndrome and so on. To analyze pulse wave continuously in sleep of CFS patients by laser blood flowmeter, we set base line component (0.01-0.08 Hz) and pulse wave component(0.70-1.50 Hz). Results of FFT analysis indicate that the CFS can have at least three subtypes of pulse dynamics in sleep. There probably are different types of illnesses now contained within the CFS construct, in which identifying subtypes of sleep disturbance can be one important key.

Electrogastrography abnormality in eating disorders.

Eating disorders are common psychiatric disorders in young women. The aim of the present study was to evaluate the gastric electrical activity of patients with eating disorders and its relation to their symptoms. The electrogastrography (EGG) was performed before and after a water load test for outpatients with eating disorders (n = 36; 14 anorexia nervosa, 14 bulimia nervosa, eight eating disorder not otherwise specified) and healthy women (n = 19). A structured interview (Eating Disorder Examination) was used to assess clinical symptoms. The percentage of normal gastric myoelectrical power was significantly smaller in the eating disorder patients (44.5% vs 74.2%; P < 0.05), while the percentage of bradygastric power was significantly greater, both before and after the water load test compared with the control subjects (30.4% vs 10.4%; P < 0.05). In addition, moderate correlation was found between the duration of illness and the percentage of bradygastria (P < 0.05). In conclusion, it is suggested that longstanding abnormal eating in patients with eating disorders may induce disturbances to gastric motor function, resulting in their abnormal, eating-related behavior, and form a symptomatic vicious circle. The EGG may be a promising method for determining the pathophysiology of eating disorders and for developing effective therapeutic approaches.

Sleep characteristics of menopausal insomnia: a polysomnographic study.

Although menopausal insomnia is of clinical significance, the essential features of this form of disrupted sleep are poorly understood. The aim of the present study was to identify the sleep characteristics of menopausal insomnia by using overnight polysomnography (PSG). Twenty-one subjects with menopausal insomnia (MI) and 13 sex- and age-matched normal control (NC) subjects without sleep complaints took part in the present study. All MI and NC subjects underwent PSG on two consecutive nights. In comparison with NC, MI subjects had non-specific findings such as significantly shorter total sleep time, longer sleep latency, higher wake time after sleep onset, and lower sleep efficiency. As for rapid eye movement (REM) sleep variables, MI subjects had significantly shorter total REM sleep time, fewer numbers of REM sleep periods, longer REM latency, and higher REM density than did the NC subjects. As for the time course of REM density, REM density during the first 3 h period of nocturnal sleep was significantly higher for MI than for NC subjects. Unlike NC subjects, REM density for MI subjects did not tend to rise progressively during nocturnal sleep. The MI subjects had objective evidence of disrupted sleep and the most striking characteristics of this dysfunction were observed in REM sleep variables. The sleep characteristics of MI subjects were found to differ in REM sleep variables from those of patients with major depression (except for REM density). Menopausal insomnia patients appear to be similar to patients with generalized anxiety disorder accompanied by severe sleep disruption. These data lend support to the clinical distinction between menopausal insomnia and insomnia associated with major psychiatric disorders.

Dominant localization of adenosine deaminase in leptomeninges and involvement of the enzyme in sleep.

Adenosine is an endogenous hypnotic molecule. However, the mechanism by which the level of extracellular adenosine is regulated remains to be elucidated. We found by Northern hybridization and enzyme assay that ecto-5(')-nucleotidase and adenosine deaminase (ADA), major enzymes responsible for the production and degradation of adenosine, respectively, were localized most abundantly in the leptomeninges within the rat brain. Immunohistochemical study showed that ADA was dominantly localized in arachnoid barrier and trabecular cells of the leptomeninges. In vivo microdialysis demonstrated that externally applied adenosine was rapidly metabolized by ADA to inosine in the subarachnoid space. Perfusion of an ADA inhibitor, coformycin, increased the extracellular adenosine level in the subarachnoid space under the rostral basal forebrain. When coformycin was continuously infused into the subarachnoid space, non-rapid eye movement sleep was increased with prolonged duration of the sleep episode. These results demonstrate that the leptomeninges control the extracellular level of adenosine in the subarachnoid space by their high 5(')-nucleotidase and ADA activities and regulate non-rapid eye movement sleep.

Clinical significance of pulse rate rise during sleep as a screening marker for the assessment of sleep fragmentation in sleep-disordered breathing.

OBJECTIVE: To assess the clinical utility of the frequencies of transient increases of pulse rate, non-invasively measured with a pulseoximeter, as an indirect indication of the degree of cortical arousal, measured conventionally on an electroencephalogram (EEG), in obstructive sleep apnea-hypopnea syndrome (OSAHS) patients. PATIENTS AND METHODS: Thirty-three consecutive patients referred with suspected OSAHS were studied. Polysomnography (PSG) with determination of esophageal pressure (Pes) and pulseoximetry was monitored to identify breathing-related EEG arousal (B-Ar) associated with apnea, hypopnea or respiratory effort and the frequencies of pulse rate increases. We also assessed the association of B-ArI (defined as the number of B-Ar per hour) with the pulse rate rise index (PRRI)-X(X=4-10) (defined as the number of pulse rate increases per hour). In addition, the sensitivity and specificity of PRRI for the assessment of a B-ArI cutoff point of 30 were calculated. RESULTS: The sensitivity and specificity of pulseoximetry for different thresholds of PRRI-X(X=4-10) demonstrated that the greatest diagnostic accuracy for detecting frequent arousal (B-ArI > or =30) occurs at a cutoff point of 40 PRRI-6 with a sensitivity of 0.88 and specificity of 0.86. This point shows a significant area under the curve of 0.84. In addition, a statistically significant correlation between PRRI-6 and B-ArI (r=0.68, P<0.0001) was observed. CONCLUSIONS: The transient increases in pulse rate measured by pulseoximetry during sleep may be a useful clinical marker for predicting the degree of arousal in OSAHS patients, and may, in addition, prevent cases with frequent respiratory effort related arousals from being overlooked. However, further studies are required to improve the confidence level of the PRRI and to investigate the causes of overestimation of EEG arousals.

Three components of obstructive sleep apnea/hypopnea syndrome.

The aims of this study were to calculate the apnea-hypopnea index (AHI), which represented as the number of apnea-hypopnea occurrences per hour, the 4% oxygen desaturation index (ODI4) and the breathing-related arousal index (B-ArI) in polysomnographic studies of obstructive sleep apnea/hypopnea syndrome (OSAHS) patients and to investigate whether there was any relationship between each pair of scoring schemes. Thirty-four cases of OSAHS were studied. Total OSAHS patients were subdivided into those with a high AHI (> 25), and those with a low AHI (< 25). The correlation between each pair of scoring schemes for OSAHS with a high AHI showed high value. The correlation between AHI and ODI4 for OSAHS with a low AHI was 0.18 and that between AHI and B-ArI showed a weak correlation of 0.59, while that between ODI4 and B-ArI was only -0.078. Our results mean that oxygen desaturation and arousal occur separately in mild or moderate OSAHS patients, even though they are diagnosed with the same level of OSAHS by means of AHI. Breathing-related arousal without oxygen desaturation often occurs in mild or moderate OSAHS patients. We previously reported that AHI does not accurately reflect the severity of the increase in negativity of esophageal pressure manifested as respiratory efforts. We consider that the comprehension and assessment of OSAHS can be improved by the systematic differentiations among the three components: oxygen desaturation, arousals and respiratory efforts.