Mild-to-moderate obstructive sleep apnea and mortality risk in a general population sample: The modifying effect of age and cardiovascular/cerebrovascular comorbidity.

About 5.4%-45.7% of the general population has mild-to-moderate obstructive sleep apnea (mmOSA), which is highly comorbid with cardiovascular and/or cerebrovascular diseases (CBVD). We examined the association between mmOSA and all-cause mortality and the modifying effect of age and CBVD. A total of 1681 adults 20-88 years old from the Penn State Adult Cohort (PSAC) (41.9% male) were followed up for 20.1 ± 6.2 years for all-cause mortality. Mild and moderate OSA were defined as an apnea/hypopnea index (AHI) 5-14.9 and 15-29.9 events/hour, respectively. CBVD was defined as a report of a physician diagnosis or treatment for heart disease and/or stroke. Cox proportional hazards regression models were used to estimate all-cause mortality adjusted for confounders. All-cause mortality risk was significantly increased in the mmOSA group in young and middle-aged adults (<60 years) (HR = 1.59, 95%CI 1.08-2.04) but not in older adults (≥60 years) (HR = 1.05, 95%CI 0.80-1.39). A synergistic effect between mmOSA and CBVD was stronger in those <60 years (HR = 3.82, 95%CI 2.25-6.48 in <60 years vs 1.86 95%CI 1.14-3.04 in ≥60 years). There was an additive effect between moderate OSA and hypertension in <60 but not in those ≥60 years. Mild OSA was associated with all-cause mortality only in the presence of CBVD. Mortality risk is increased in young and middle-aged adults with moderate OSA, whereas the mortality risk associated with mild OSA is elevated only, regardless of age, in the presence of comorbid CBVD. AHI cut-offs warranting treatment of mmOSA may need to be adjusted based on age and comorbidities.

Insomnia with objective short sleep duration is associated with hypertension.

Insomnia with objective short sleep duration has been proposed as the most biologically severe phenotype of the disorder associated with cardiometabolic morbidity in population-based samples. In this study, we investigated the association between insomnia with objective short sleep duration and hypertension in a large clinical sample. We studied 348 patients diagnosed with chronic insomnia disorder based on International Classification of Sleep Disorders Third Edition criteria and 150 normal sleepers. Objective short sleep duration was defined by the median total sleep time of the sample (< 7 hr) measured with 1-night polysomnography. Hypertension was defined based on blood pressure levels, antihypertensive medication use and/or a physician diagnosis. After adjusting for potential confounders, patients with chronic insomnia disorder who slept < 7 hr were associated with 2.8-fold increased odds of hypertension compared with normal sleepers who slept ≥ 7 hr (odds ratio = 2.81, 95% confidence interval = 1.068-7.411) or < 7 hr (odds ratio = 2.75, 95% confidence interval = 1.005-7.542), whereas patients with chronic insomnia disorder who slept ≥ 7 hr (odds ratio = 1.52, 95% confidence interval = 0.537-4.285) or normal sleepers who slept < 7 hr (odds ratio = 1.07, 95% confidence interval = 0.294-3.904) were not significantly associated with increased odds of hypertension compared with normal sleepers who slept ≥ 7 hr. Linear regression analyses showed that, for every hour decrease in total sleep time, systolic and diastolic blood pressure increased by 1.014 mmHg (p = 0.045) and 0.923 mmHg (p = 0.015), respectively, in patients with chronic insomnia disorder but not in normal sleepers. Our findings further support that insomnia with objective short sleep duration is a risk factor for hypertension, and objective short sleep duration may be a useful marker of the biological severity of chronic insomnia disorder in clinical practice.

Short-term and intermediate-term fine particulate air pollution are synergistically associated with habitual sleep variability in adolescents - A cross-sectional study.

BACKGROUND: Both air pollution and poor sleep have been associated with increased risk of cardiovascular diseases. However, the association between air pollution and sleep health, especially among adolescents, is rarely investigated. METHODS: To investigate the association between fine particulate (PM2.5) air pollution and habitual sleep patterns, we analyzed data obtained from 246 adolescents who participated in the Penn State Child Cohort follow-up examination. We collected their individual-level 24-h (short-term) PM2.5 concentration by using a portable monitor. We estimated their residential-level PM2.5 concentration during the 60-day period prior to the examination (intermediate-term) using a kriging approach. Actigraphy was used to measure participants' sleep durations for seven consecutive nights. Habitual sleep duration (HSD) and sleep variability (HSV) were calculated as the mean and SD of the seven-night sleep duration. Multivariable-adjusted linear regression models were used to assess the association between PM2.5 exposures and HSD/HSV. An interaction between short-term and intermediate-term PM2.5 was created to explore their synergistic associations with HSD/HSV. RESULTS: Elevated short-term and intermediate-term PM2.5 exposure were significantly (p < 0.05) associated with higher HSV, but not HSD. Specifically, the mean (95% CI) increase in HSV associated with 1 SD higher 24-h (26.3 µg/m3) and 60-day average (2.2 µg/m3) PM2.5 were 14.6 (9.4, 14.8) and 4.9 (0.5, 9.2) minutes, respectively. In addition, there was a synergistic interaction (p = 0.08) between short-term and intermediate-term PM2.5 exposure on HSV, indicative that the association between intermediate-term PM2.5 and HSV became stronger as short-term PM2.5 increases, and vice versa. CONCLUSION: Short-term individual-level and intermediate-term residential-level PM2.5 exposures are adversely and synergistically associated with increased sleep variability, an indicator of instability of sleep quantity, in adolescents. Through such an association with sleep pattern, PM2.5 air pollution may increase long-term cardiometabolic risks.

Behavioral, neurocognitive, polysomnographic and cardiometabolic profiles associated with obstructive sleep apnea in adolescents with ADHD.

BACKGROUND: A high comorbidity between attention-deficit/hyperactivity disorder (ADHD) and obstructive sleep apnea (OSA) as well as similar impairments across neurobehavioral outcomes has been described in children. However, there is a paucity of research examining the comorbidity of these two disorders in adolescents. This study examined the association of OSA with sleep, neurobehavioral, and cardiometabolic outcomes in adolescents with ADHD from the general population. METHODS: 421 adolescents (16.9 ± 2.3 years, 53.9% male) underwent 9-hr polysomnography, neurobehavioral, and physical evaluation. ADHD was ascertained by a parent-or-self-report of a lifetime diagnosis/treatment of ADHD. OSA was defined as an apnea hypopnea index of ≥2 events/hour. Groups of controls (n = 208), OSA-alone (n = 115), ADHD-alone (n = 54), and ADHD+OSA (n = 44) were studied. Multivariable-adjusted general linear models tested group differences in PSG parameters, neurobehavioral, and cardiometabolic outcomes after controlling for sex, race/ethnicity, age, and/or body mass index percentile. RESULTS: The ADHD+OSA group had significantly longer sleep onset latency, shorter total sleep time, lower sleep efficiency, and higher percent of stage 1 sleep, as compared with all other groups, however, these differences were diminished by excluding adolescents on psychoactive medication. The ADHD-alone group showed significantly higher periodic limb movements than controls. The ADHD+OSA and ADHD-alone groups did not significantly differ on any measure of neurocognitive or behavioral functioning. The ADHD+OSA and OSA-alone groups showed significantly worse cardiometabolic and inflammatory biomarkers when compared to controls or the ADHD-alone, but did not significantly differ between each other. CONCLUSIONS: Adolescents with a diagnosis ADHD+OSA showed phenotypic risk factors for OSA (i.e., overweight/obesity, visceral adiposity, metabolic syndrome, and inflammation) but not worse neurobehavioral outcomes when compared with ADHD-alone. While comorbidity is possible, these data support that adolescents with a suspicion of ADHD should be screened for OSA, before a diagnosis is reached and psychoactive medication initiated.

Hypothalamic-pituitary-adrenal (HPA) axis response to exogenous corticotropin-releasing hormone (CRH) is attenuated in men with chronic insomnia.

Although insomnia is by far the most common sleep disorder, our understanding of its neurobiology is limited. Insomnia, particularly when associated with objective sleep disturbance, has been associated with activation of the hypothalamic-pituitary-adrenal axis. The objective of this experimental study was to compare the response of the hypothalamic-pituitary-adrenal axis to ovine corticotropin-releasing hormone, a stress test, in men with insomnia versus controls. Circulating adrenocorticotropic hormone and cortisol levels were assayed before (-30 min, -15 min), at (0 min) and after (+5 min, +15 min, +30 min, +60 min, +90 min, +120 min) exogenous ovine corticotropin-releasing hormone administration in 23 men (11 insomnia, 12 controls), who underwent four consecutive nights of in-lab polysomnography. Men with insomnia compared with controls demonstrated markedly and significantly shorter total sleep time (368.4 ± 8.99 min versus 411.61 ± 8.61 min; p < 0.01) and lower sleep efficiency (76.77 ± 1.80% versus 86.04 ± 1.72%; p < 0.01) on polysomnography, and showed decreased adrenocorticotropic hormone and cortisol levels after ovine corticotropin-releasing hormone administration. Adrenocorticotropic hormone levels at 15 min and 30 min were significantly lower in men with insomnia than in controls (p < 0.05). Similarly, the peak levels of cortisol at +60 min, and the total and net area under the curve levels of this hormone were significantly lower in men with insomnia than controls (all p < 0.01). Adrenocorticotropic hormone and cortisol response to ovine corticotropin-releasing hormone administration was attenuated in men with insomnia associated with objective sleep disturbance, suggesting that objectively defined insomnia subtypes have a disrupted hypothalamic-pituitary-adrenal axis function and highlight the need to develop treatments targeting the underlying hypothalamic-pituitary-adrenal axis dysregulation.

Effect of trazodone versus cognitive-behavioural treatment on high- and slow-frequency activity during non-rapid eye movement sleep in chronic insomnia: A pilot, randomized clinical trial.

Trazodone and cognitive-behavioural treatment for insomnia (CBT-I) are widely used to treat patients with chronic insomnia. Although both treatments improve sleep continuity, no study has compared their comparative effectiveness in modifying spectral electroencephalographic (EEG) activity during sleep in humans. In this study, participants included 19 men and women with chronic insomnia who were randomized to either trazodone (n = 8) or CBT-I (n = 11) treatment for 3 months. We examined delta (0.39-3.91 Hz), theta (4.30-7.81 Hz), alpha (8.20-11.72 Hz), sigma (12.11-14.84 Hz), beta (15.23-35.16 Hz) and gamma (35.55-49.61 Hz) relative power during non-rapid eye movement (NREM) sleep at pre-treatment, 3- month post-treatment and 6-month follow-up. This study was registered in Clinical Trials (NCT01348542). We found trazodone but not CBT-I significantly decreased sigma (p = .041, d = 0.88; time × group p = .009) and beta (p = .005, d = 1.41; time × group p = .016) power during NREM sleep at post-treatment. Compared to CBT-I, trazodone increased delta (p = .018) and decreased sigma (p = .013) and beta (p = .023) power during NREM sleep at post-treatment. At follow-up, we did not observe significant changes in relative EEG power during NREM sleep in either the CBT-I or trazodone group compared to pre-treatment. Compared to CBT-I, trazodone decreased alpha (p = .039) and sigma (p = .009) power during NREM sleep at follow-up. In conclusion, trazodone, but not CBT-I, decreased fast-frequency EEG activity during NREM sleep. Compared to CBT-I, trazodone appears to have a stronger impact on cortical and physiological hyperarousal in patients with chronic insomnia.

Clinical Significance and Cut-Off Scores for the Pre-Sleep Arousal Scale in Chronic Insomnia Disorder: A Replication in a Clinical Sample.

Background: In contrast to pre-sleep cognitive arousal, self-reported pre-sleep somatic arousal is a rather elusive construct for which little validity has been provided. Thus, the clinical significance of somatic symptoms during the pre-sleep period remains unknown. Participants: 248 patients (45.0 ± 16.7 years old, 65.3% female) with a diagnosis of chronic insomnia disorder, out of 388 consecutive patients evaluated at the Behavioral Sleep Medicine (BSM) program of Penn State Hershey Sleep Research & Treatment Center. Methods: Participants completed the Pre-sleep Arousal Scale assessing cognitive (PSAS-C) and somatic (PSAS-S) arousal as well as the Insomnia Severity Index (ISI), Ford Insomnia Response to Stress Test (FIRST), Arousal Predisposition Scale (APS), and Depression Anxiety Stress Scale (DASS). Multivariable stepwise regression assessed which clinical factors were independently associated with greater PSAS-C and PSAS-S scores. Receiver operating characteristic analysis determined the predictive value for identifying sleep reactivity (FIRST≥18) and clinical anxiety (DASS-A ≥ 10) and clinically useful cutoff scores. Results: The strongest correlates of PSAS-S were DASS-A (ß = 0.64) and chronic pain (ß = 0.11), while those of PSAS-C were FIRST (ß = 0.29) and a history of stroke (ß = 0.10). A PSAS-S score of 14.8 (AUC = 0.87, 95%CI = 0.83-0.91) and a PSAS-C score of 24.5 (AUC = 0.82, 95%CI = 0.76-0.88) showed the best balance in specificity and sensitivity to identify clinical anxiety and sleep reactivity, respectively. Conclusions: Self-reported pre-sleep somatic symptoms are a marker of comorbid anxiety and, potentially chronic pain, impacting nighttime sleep. The optimal cutoff scores of 14 and 20 proposed herein can help clinicians with case formulation, with tailoring BSM treatments and their targets.

Childhood high-frequency EEG activity during sleep is associated with incident insomnia symptoms in adolescence.

BACKGROUND: Insomnia has been associated in cross-sectional studies with increased beta (15-35 Hz) electroencephalogram (EEG) power during nonrapid eye movement (NREM) sleep, an index of cortical hyperarousal. However, it is unknown whether this cortical hyperarousal is present before individuals with insomnia develop the disorder. To fill this gap, we examined the association of childhood sleep high-frequency EEG activity with incident insomnia symptoms (i.e., absence of insomnia symptoms in childhood but presence in adolescence). METHODS: We studied a case-control subsample of 45 children (6-11 years) from the Penn State Child Cohort, a population-based random sample of 421 children, who were followed up after 8 years as adolescents (13-20 years). We examined low-beta (15-25 Hz) and high-beta (25-35 Hz) relative power at central EEG derivations during NREM sleep and, in secondary analyses, during sleep onset latency, sleep onset, and REM sleep. Incident insomnia symptoms were defined as the absence of parent-reported difficulty falling and/or staying asleep during childhood and a self-report of these insomnia symptoms during adolescence. RESULTS: Childhood high-beta power during NREM sleep was significantly increased in children who developed insomnia symptoms in adolescence (n = 25) as compared to normal sleeping controls (n = 20; p = .03). Multivariable-adjusted logistic regression models showed that increased childhood high-beta EEG power during NREM sleep was associated with a threefold increased odds (95% CI = 1.12-7.98) of incident insomnia symptoms in adolescence. No other significant relationships were observed for other sleep/wake states or EEG frequency bands. CONCLUSIONS: Increased childhood high-frequency EEG power during NREM sleep is associated with incident insomnia symptoms in adolescence. This study indicates that cortical hyperarousal during sleep may be a premorbid neurophysiological sign of insomnia, which may mediate the increased risk of psychiatric disorders associated with insomnia.

Am I (hyper)aroused or anxious? Clinical significance of pre-sleep somatic arousal in young adults.

Self-reported somatic arousal remains a challenging clinical construct, particularly because only a subset of patients report symptoms such as racing heart, palpitations or increased body temperature interfering with their sleep. It is unclear whether self-reported somatic arousal is a marker of hyperarousal or co-morbid clinical anxiety in individuals with insomnia. Participants included 196 young adults aged 20.2 ±â€…1.0 years old who were predominantly females (75%). About 39% of the sample reported subthreshold insomnia, and about 8% reported clinically significant insomnia, based on their Insomnia Severity Index. Participants completed the Pre-Sleep Arousal Scale, Beck Anxiety Inventory, Beck Depression Inventory, Arousal Predisposition Scale, and Ford Insomnia Response to Stress Test. Multivariable stepwise regression assessed which factors were independently associated with pre-sleep cognitive (Pre-Sleep Arousal Scale-Cognitive) and somatic (Pre-Sleep Arousal Scale-Somatic) arousal. Receiver-operating characteristic analysis assessed the predictive value to identify clinically significant anxiety (Beck Anxiety Inventory ≥ 20), insomnia (Insomnia Severity Index ≥ 15) and arousability (Arousal Predisposition Scale ≥ 32). Beck Anxiety Inventory (ß = 0.42) was the best single correlate of Pre-Sleep Arousal Scale-Somatic, while Insomnia Severity Index (ß = 0.33) was of Pre-Sleep Arousal Scale-Cognitive. A Pre-Sleep Arousal Scale-Somatic score of 12 or more identified those with clinically significant anxiety with 65% specificity and 65% sensitivity, while a cut-off score of 14 increased its sensitivity (86%). Self-reported pre-sleep somatic arousal may be an index of co-morbid clinical anxiety in individuals with insomnia. These findings aid clinicians with assessment and treatment, particularly in the absence of clinical guidelines indicating when somatically focused relaxation techniques should be included as part of multicomponent cognitive behavioural treatment of insomnia.

Increased inflammation from childhood to adolescence predicts sleep apnea in boys: A preliminary study.

While chronic systemic inflammation in obstructive sleep apnea (OSA) has been traditionally considered a consequence of intermittent hypoxia, several treatment studies targeting inflammation suggest that this process may precede the development of the disorder. A recent cross-sectional study in the Penn State Child Cohort (PSCC) revealed that inflammation largely mediates the association between visceral adiposity and OSA in adolescence. The purpose of this study was to examine for the first time whether, longitudinally, inflammation precedes OSA during this developmental period. A subsample of the PSCC with longitudinal sleep and inflammation data (n=51) was included in this study. Participants underwent 9-h polysomnography (22:00-7:00), physical exam, and fasting morning blood draw at both time points. Plasma C-reactive protein (CRP) was measured via ELISA. At follow-up, visceral, subcutaneous, and total fat area were assessed via dual X-ray absorptiometry. Sex differences in body composition emerged in adolescence, with boys having more visceral adiposity than girls. Longitudinal increases in waist circumference from childhood to adolescence were associated with increases in CRP (ΔCRP) and follow-up CRP in boys, but not girls. Furthermore, in boys, ΔCRP was associated with higher follow-up apnea/hypopnea index (AHI). When ΔCRP was entered into a model predicting follow-up AHI, Δwaist circumference was no longer significant, indicating that inflammation largely explains the association between increasing central obesity and OSA severity. These preliminary findings, in a longitudinal, non-clinical sample of children developing OSA, suggest that inflammation derived from visceral adipose tissue precedes the development of the disorder, suggesting a potential causal mechanism.

Insomnia symptoms with objective short sleep duration are associated with systemic inflammation in adolescents.

Inflammation has been suggested as a potential pathway by which insomnia and short sleep can affect risk of morbidity in adults. However, few studies have examined the association of insomnia with inflammation in adolescents, despite accumulating evidence that pathophysiologic changes may already occur during this critical developmental period. The present study sought to examine the association of insomnia symptoms with systemic inflammation and the role of objective sleep duration in this association. Participants were 378 adolescents (16.9±2.3y, 45.8% female) from the Penn State Child Cohort, a population-based sample who underwent 9-h polysomnography (PSG) followed by a single fasting blood draw to assess plasma levels of C-reactive protein (CRP) and other inflammatory markers. Insomnia symptoms were defined by a self-report of difficulties falling and/or staying asleep, while objective sleep duration groups were defined as a PSG total sleep time ⩾8, 8-7, and ⩽7h. We assessed the association of insomnia symptoms, objective sleep duration, and their interaction with inflammatory markers, while adjusting for multiple potential confounders. Adolescents reporting insomnia symptoms had significantly higher levels of CRP compared to controls and a significant interaction (p<0.01) showed that objective sleep duration modified this association. Elevated CRP was present in adolescents with insomnia symptoms and ⩽7h of sleep (1.79mg/L) as compared to controls or adolescents with insomnia symptoms and ⩾8h of sleep (0.90mg/L and 0.98mg/L, respectively) or controls with ⩽7h of sleep (0.74mg/L; all p-values <0.01). In sum, insomnia symptoms with objective short sleep duration are associated with systemic inflammation as early as adolescence. This study suggests that chronic low-grade inflammation may be a common final pathway towards morbidity in adulthood in this insomnia phenotype.

Internet use, eHealth literacy and attitudes toward computer/internet among people with schizophrenia spectrum disorders: a cross-sectional study in two distant European regions.

BACKGROUND: Individuals with schizophrenia spectrum disorders use the Internet for general and health-related purposes. Their ability to find, understand, and apply the health information they acquire online in order to make appropriate health decisions - known as eHealth literacy - has never been investigated. The European agenda strives to limit health inequalities and enhance mental health literacy. Nevertheless, each European member state varies in levels of Internet use and online health information-seeking. This study aimed to examine computer/Internet use for general and health-related purposes, eHealth literacy, and attitudes toward computer/Internet among adults with schizophrenia spectrum disorders from two distant European regions. METHODS: Data were collected from mental health services of psychiatric clinics in Finland (FI) and Greece (GR). A total of 229 patients (FI = 128, GR = 101) participated in the questionnaire survey. The data analysis included evaluation of frequencies and group comparisons with multiple linear and logistic regression models. RESULTS: The majority of Finnish participants were current Internet users (FI = 111, 87%, vs. GR = 33, 33%, P < .0001), while the majority of Greek participants had never used computers/Internet, mostly due to their perception that they do not need it. In both countries, more than half of Internet users used the Internet for health-related purposes (FI = 61, 55%, vs. GR = 20, 61%). The eHealth literacy of Internet users (previous and current Internet users) was found significantly higher in the Finnish group (FI: Mean = 27.05, SD 5.36; GR: Mean = 23.15, SD = 7.23, P < .0001) upon comparison with their Greek counterparts. For current Internet users, Internet use patterns were significantly different between country groups. When adjusting for gender, age, education and disease duration, country was a significant predictor of frequency of Internet use, eHealth literacy and Interest. The Finnish group of Internet users scored higher in eHealth literacy, while the Greek group of never Internet users had a higher Interest in computer/Internet. CONCLUSIONS: eHealth literacy is either moderate (Finnish group) or low (Greek group). Thus, exposure to ICT and eHealth skills training are needed for this population. Recommendations to improve the eHealth literacy and access to health information among these individuals are provided.

Inflammation mediates the association between visceral adiposity and obstructive sleep apnea in adolescents.

Only a handful of studies, primarily in clinical samples, have reported an association between obesity, inflammation, and obstructive sleep apnea (OSA) in children and adolescents. No studies, however, have examined the pathogenetic link between visceral adiposity, systemic inflammation, and incident OSA in a large general population sample using objective measures of sleep and body fat. Adolescents (n = 392; mean age 17.0 ± 2.2 yr, 54.0% male) from the Penn State Child Cohort (PSCC) underwent 9-h overnight polysomnography; a DXA scan to assess body fat distribution; and a single fasting blood draw for the assessment of plasma interleukin-6 (IL-6), IL-6 soluble receptor (IL-6 sR), tumor necrosis factor alpha (TNFα), tumor necrosis factor receptor 1A (TNFR1), C-reactive protein (CRP), leptin, and adiponectin levels via ELISA. Visceral fat area was significantly elevated in moderate OSA (AHI ≥ 5), especially in boys. IL-6, CRP, and leptin were highest in adolescents with moderate OSA, even after adjusting for BMI percentile. Mediation analysis revealed that 42% of the association between visceral fat and OSA in adolescents was mediated by IL-6 (p = 0.03), while 82% of the association was mediated by CRP (p = 0.01). These data are consistent with the model of a feed-forward, vicious cycle, in which the release of proinflammatory cytokines by visceral adipocytes largely explains the association between central obesity and OSA; in turn, inflammation is also elevated in OSA independent of BMI. These findings, in a large, representative, non-clinical sample of young people, add to our understanding of the developmental pathogenesis of sleep apnea.

Sleep apnoea and the hypothalamic-pituitary-adrenal axis in men and women: effects of continuous positive airway pressure.

Previous findings on the association of obstructive sleep apnoea (OSA) and the hypothalamic-pituitary-adrenal (HPA) axis are inconsistent, partly due to the confounding effect of obesity and infrequent sampling. Our goal was to examine whether in a relatively nonobese population, OSA is associated with elevated cortisol levels and to assess the effects of a 2-month placebo-controlled continuous positive airway pressure (sham-CPAP) use.72 subjects (35 middle-aged males and post-menopausal females with OSA, and 37 male and female controls) were studied in the sleep laboratory for four nights. 24-h blood sampling was performed every hour on the fourth day and night in the sleep laboratory at baseline, after sham-CPAP and after CPAP treatment.In both apnoeic men and women, OSA was associated with significantly higher 24-h cortisol levels compared with controls, whereas CPAP lowered cortisol levels significantly, close to those of controls.These results suggest that OSA in nonobese men and slightly obese women is associated with HPA axis activation, similar albeit stronger compared with obese individuals with sleep apnoea. Short-term CPAP use decreased cortisol levels significantly compared with baseline, indicating that CPAP may have a protective effect against comorbidities frequently associated with chronic activation of the HPA axis, e.g. hypertension.

Natural history of sleep disordered breathing in prepubertal children transitioning to adolescence.

Because there is a lack of agreed upon diagnostic criteria, it is critical to understand the natural history of obstructive sleep apnoea (OSA) in children in order to establish treatment strategies based on objective data.The Penn State Child Cohort is a representative, general-population sample of 700 elementary school children at baseline, of whom 421 were reassessed 8 years later, during adolescence.The remission of childhood apnoea-hypopnoea index (AHI) ≥2 events per h in adolescence was 52.9%. Using the higher threshold of AHI ≥5 events per h, remission was 100.0%, with 50.0% partially remitting to AHI 2- <5 events per h and the other half remitting to AHI <2 events per h. The incidence of adolescent AHI ≥2 events per h in those with childhood AHI <2 events per h was 36.5%, while the incidence of AHI ≥5 events per h in those with childhood AHI <5 events per h was 10.6%. This longitudinal study confirms that prepubertal OSA tends to resolve naturally during the transition to adolescence, and that primary snoring and mild sleep disordered breathing (SDB) do not appear to be strongly associated with progression to more severe SDB.The key risk factors for SDB in adolescence are similar to those found in middle-aged adults (i.e. male sex, older age and obesity). Moreover, consistent with recent studies in adults, this study includes the novel cross-sectional finding that visceral fat is associated with SDB as early as adolescence.

Family Functioning in First-Episode and Chronic Psychosis: The Role of Patient's Symptom Severity and Psychosocial Functioning.

The aim of the present study was to assess the relationship between illness-related characteristics, such as symptom severity and psychosocial functioning, and specific aspects of family functioning both in patients experiencing their first episode of psychosis (FEP) and chronically ill patients. A total of 50 FEP and 50 chronic patients diagnosed with schizophrenia or bipolar disorder (most recent episode manic severe with psychotic features) and their family caregivers participated in the study. Family functioning was evaluated in terms of cohesion and flexibility (FACES IV Package), expressed emotion (FQ), family burden (FBS) and caregivers' psychological distress (GHQ-28). Patients' symptom severity (BPRS) and psychosocial functioning (GAS) were assessed by their treating psychiatrist within 2 weeks from the caregivers' assessment. Increased symptom severity was associated with greater dysfunction in terms of family cohesion and flexibility (ß coefficient -0.13; 95 % CI -0.23, -0.03), increased caregivers' EE levels on the form of emotional overinvolvement (ß coefficient 1.03; 95 % CI 0.02, 2.03), and psychological distress (ß coefficient 3.37; 95 % CI 1.29, 5.45). Family burden was found to be significantly related to both symptom severity (ß coefficient 3.01; 95 % CI 1.50, 4.51) and patient's functioning (ß coefficient -2.04; 95 % CI -3.55, -0.53). No significant interaction effect of chronicity was observed in the afore-mentioned associations. These findings indicate that severe psychopathology and patient's low psychosocial functioning are associated with poor family functioning. It appears that the effect for family function is significant from the early stages of the illness. Thus, early psychoeducational interventions should focus on patients with severe symptomatology and impaired functioning and their families.

Gender differences in the association of sleep apnea and inflammation.

Over the last 15years, many studies have established an association of sleep apnea with inflammation and metabolic aberrations. However, no controlled studies have examined potential gender effects in this association. We recruited 120 middle-aged, predominantly non-obese mild-to-moderate sleep apneics and controls (62 males, 58 females). All participants underwent a clinical history, physical examination, and 1-night 8-h polysomnography recording and provided a single fasting blood sample for assessment of interleukin-6 (IL-6), tumor necrosis factor receptor 1 (TNFR1), C-reactive protein (CRP), leptin, and adiponectin levels. Among non-sleep apneics, females had higher levels of TNFR1 (p=0.01), CRP (p=0.005), leptin (p<0.001), and adiponectin (p<0.001) compared to males, independent of age and body mass index. When analyzed separately by gender, sleep apneic men had elevated TNFR1 (p=0.04), CRP (p=0.06) and IL-6 (p=0.11) relative to control men; in sleep apneic females, only CRP was elevated (p=0.04). Furthermore, CRP was associated with apnea severity in a dose-response manner (p-linear=0.04 in both genders) and was independently associated with comorbid hypertension in apnea (p-linear=0.005 for women; p-linear=0.09 for men). In conclusion, although women have naturally higher levels of inflammatory and metabolic markers than men, sleep apneic men appear to have a more severe inflammatory profile compared to women. Our findings suggest that these markers should be analyzed and interpreted separately in men and women, and that a single measure of plasma CRP appears to be a clinically-useful marker of apnea severity and comorbid cardiovascular morbidity.

Insomnia and incident depression: role of objective sleep duration and natural history.

Longitudinal studies that have examined the association of insomnia with incident depression using objective sleep measures are very limited. The aim of this study was to examine the predictive role of the severity of insomnia for incident depression in a general population sample using psychometric and polysomnographic data. From a random, general population sample of 1741 individuals of the Penn State Adult Cohort, 1137 adults without depression were followed up with a structured telephone interview after 7.5 years. All subjects completed a full medical evaluation, 1-night polysomnogram and Multiphasic Minnesota Personality Inventory at baseline. The incidence of depression was 15%. Poor sleep (odds ratio = 1.5, P = 0.001) and insomnia (odds ratio = 1.9, P = 0.031) were significantly associated with incident depression. The odds of incident depression were highest (odds ratio = 2.2, P = 0.019) in insomnia with objective short sleep duration and independent of Multiphasic Minnesota Personality Inventory Ego Strength scores, an index of poor coping resources. The persistence of insomnia and worsening of poor sleep into insomnia significantly increased the odds of incident depression (odds ratios ranged from 1.8 to 6.3), whereas their full remission did not (odds ratio ranged from 1.2 to 1.8). Insomnia with short sleep duration is associated with incident depression independent of poor coping resources, whereas the association of insomnia with normal sleep duration with incident depression was mediated by poor coping resources. Persistence and worsening of poor sleep or insomnia, but not their full remission, are significant predictors of incident depression. These data suggest that there is a significant relationship between the severity of insomnia and incident depression.

Chronic fatigue syndrome and fibromyalgia in diagnosed sleep disorders: a further test of the 'unitary' hypothesis.

BACKGROUND: Since chronic fatigue syndrome (CFS) and fibromyalgia (FM) often co-exist, some believe they reflect the same process, somatization. Against that hypothesis are data suggesting FM but not CFS was common in patients with sleep-disordered breathing (SDB). The presence of discrete case definitions for CFS and FM allowed us to explore rates of CFS alone, CFS with FM, and FM alone in SDB patients compared to those with sleep complaints that fulfilled criteria for insomnia. METHODS: Participants were 175 sequential patients with sleep-related symptoms (122 had SDB and 21 had insomnia) and 39 healthy controls. Diagnoses were made by questionnaires, tender point count, and rule out labs; sleepiness was assessed with Epworth Sleepiness Scale and mood with Beck Depression Inventory. RESULTS: Rates of CFS, FM or CFS + FM were high: 13% in SDB and 48% in insomnia. CFS occurred frequently in SDB and insomnia, but FM occurred frequently only in insomnia. SDB patients with CFS and/or FM had higher daytime sleepiness than those without these disorders. CONCLUSION: CFS patients should complete Epworth scales, and sleep evaluation should be considered for those with scores ≥ 16 before receiving the diagnosis of CFS; the coexistence of depressed mood in these patients suggests some may be helped by treatment of their depression. That FM was underrepresented in SDB suggests FM and CFS may have different underlying pathophysiological causes.