Spindles are highly heritable as identified by different spindle detectors.

STUDY OBJECTIVES: Sleep spindles, a defining feature of stage N2 sleep, are maximal at central electrodes and are found in the frequency range of the electroencephalogram (EEG) (sigma 11-16 Hz) that is known to be heritable. However, relatively little is known about the heritability of spindles. Two recent studies investigating the heritability of spindles reported moderate heritability, but with conflicting results depending on scalp location and spindle type. The present study aimed to definitively assess the heritability of sleep spindle characteristics. METHODS: We utilized the polysomnography data of 58 monozygotic and 40 dizygotic same-sex twin pairs to identify heritable characteristics of spindles at C3/C4 in stage N2 sleep including density, duration, peak-to-peak amplitude, and oscillation frequency. We implemented and tested a variety of spindle detection algorithms and used two complementary methods of estimating trait heritability. RESULTS: We found robust evidence to support strong heritability of spindles regardless of detector method (h2 > 0.8). However not all spindle characteristics were equally heritable, and each spindle detection method produced a different pattern of results. CONCLUSIONS: The sleep spindle in stage N2 sleep is highly heritable, but the heritability differs for individual spindle characteristics and depends on the spindle detector used for analysis.

Candidate gene analysis in the São Paulo Epidemiologic Sleep Study (EPISONO) shows an association of variant in PDE4D and sleepiness.

INTRODUCTION: Sleepiness and cardiovascular disease share common molecular pathways; thus, genetic risk factors for sleepiness may also predict cardiovascular disease risk. This study explored the associations between subjective sleepiness and single-nucleotide polymorphisms (SNPs) in candidate genes within oxidative stress, inflammatory, and neuronal pathways, which may contribute to sleepiness and downstream cardiovascular disease risk: Cytochrome B-245, Alpha Polypeptide (CYBA), Cytochrome B-245, Beta Polypeptide (CYBB), Neutrophil Cytosolic Factor (NCF2), Tumor Necrosis Factor-Alpha (TNFA), and Phosphodiesterase 4D (PDE4D). METHODS: Adults (N = 918) from the general population who were a part of the São Paulo Epidemiologic Sleep Study (EPISONO) in São Paulo, Brazil, were genotyped using Human Omni Express BeadChip array. The average age was 42 ± 14.5 years, subjects had a mean body mass index (BMI) of 26.9 ± 5.4 kg/m2, and 44% were male. Based on the Epworth Sleepiness Scale (ESS), subjects were classified as having sleepiness (ESS ≥ 10) or no sleepiness (ESS < 10). Logistic regression models were used to examine the associations with SNPs within candidate genes and sleepiness, adjusting for age, gender, BMI, Apnea-Hypopnea Index (AHI), total sleep time, and ancestry informative principal components (PCs). Complementary analyses using linear regression to assess the relationship between SNPs and continuous ESS were performed. RESULTS: We observed a novel association between the C allele of the rs12522161 SNP on PDE4D and a decreased likelihood of sleepiness, controlling for covariates and ancestry [OR (95% CI) = 0.64 (0.50, 0.81); p = 0.0002]. CONCLUSION: We present data for a novel genetic association with sleepiness for an SNP on the PDE4D gene, rs12522161.

Altered diurnal states in insomnia reflect peripheral hyperarousal and metabolic desynchrony: a preliminary study.

Study Objectives: Insomnia is a common sleep disorder that is associated with a range of adverse outcomes. Patients with insomnia exhibit hyperarousal in multiple domains, including an elevated metabolic rate, but specific metabolic molecular perturbations are unknown. Furthermore, objective clinical markers of insomnia are not available and current assessment of pathological extent relies on self-report. Here, we provide preliminary evidence that chronic insomnia is remarkably reflected in the periphery through detailed metabolic assessments. Methods: Serum from confirmed patients with insomnia and matched good sleepers (n = 15 per group) was sampled at high temporal resolution (every 2 hr over 48 hr). Food intake was controlled by providing hourly isocaloric snacks, and sleep architecture was assessed by overnight polysomnography. Quantitative metabolic assessments were conducted using nuclear magnetic resonance spectroscopy. Results: Global metabolic profiles differentiated patients with insomnia from healthy controls, with elevated amino acid and energy metabolites and reduced branched-chain amino acid catabolic products. Strikingly, branched-chain amino acid catabolism was found to be specifically altered during the night with ~10 per cent increased accumulation of glucose in insomnia patients. Rhythmicity analysis revealed 11 metabolites that cycled diurnally across both groups, with phase advances noted for acetone and delays for lactate and branched-chain amino acids and their products. Conclusions: These preliminary observations suggest that insomnia is associated with quantitative metabolic dysregulation and supports the hyperarousal hypothesis. Furthermore, we posit that these changes lead to a state of metabolic desynchrony in insomnia that is involved in the pathophysiology of the disorder and/or mediates its impact on health outcomes. Clinical Trials Registration: NCT01957111.

Targets for the Treatment of Insomnia in Veterans With Serious Mental Illness.

STUDY OBJECTIVES: Insomnia is pervasive among people with serious mental illnesses (SMI) and has a profound negative impact on their psychiatric symptom management and recovery. However, little is known about the factors that affect severity of insomnia in those with SMI. In addition, very few studies have explored whether evidence-based interventions developed for those without SMI are appropriate for or applicable to individuals with SMI. The purpose of this study was to test the role of arousal, dysfunctional cognitions about sleep, and sleep-related behaviors in predicting severity of insomnia in a sample of 60 Veterans who were receiving care in Veterans Health Administration mental health and psychosocial rehabilitation programs and who reported subjective insomnia. In addition, information was collected regarding the types of insomnia treatments provided to these Veterans. METHODS: Participants completed assessments of insomnia severity and sleep-related arousal, behaviors, and cognitions. Medical records were reviewed to determine whether participants had been screened/assessed for insomnia and whether treatments for insomnia were provided before the date of referral to the study. Multiple regression was used to predict insomnia severity on the basis of these factors. RESULTS: Most participants (81.7%) reported moderate to severe insomnia, although only 3.3% had a diagnosis of insomnia in their medical records. Worry and helplessness about sleep were predictive of insomnia severity; better self-reported sleep hygiene and higher levels of arousal were also associated with greater severity of insomnia. Education about sleep hygiene and medication were the only types of insomnia treatment received. CONCLUSIONS: Similar to insomnia among individuals without SMI, insomnia in Veterans with SMI is associated with dysfunctional sleep-related behaviors and cognitions. Many of the Veterans also lacked access to settings and resources conducive to healthy sleep. Veterans with SMI should be regularly assessed for insomnia. Research is needed concerning optimal evidence-based insomnia interventions for addressing behaviors and cognitions in this population in the context of these challenges.

Predeployment Sleep Duration and Insomnia Symptoms as Risk Factors for New-Onset Mental Health Disorders Following Military Deployment.

STUDY OBJECTIVES: To evaluate predeployment sleep duration and insomnia symptoms in relation to the development of mental health symptoms. DESIGN: Longitudinal cohort study. SETTING: The Millennium Cohort Study survey is administered via a secure website or US mail. PARTICIPANTS: Data were from 15,204 participants who completed their first deployment between the submissions of 2 consecutive Millennium Cohort questionnaires (2001-2008). INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Using self-reported data from the Millennium Cohort Study we evaluated the association of predeployment sleep duration and insomnia symptoms on the development of new-onset mental disorders among deployers. Multivariable logistic regression was used to estimate the odds of developing posttraumatic stress disorder (PTSD), depression, and anxiety, while adjusting for relevant covariates including combat-related trauma. The study outcomes were assessed using validated instruments, including the PTSD checklist-civilian version, and the PRIME-MD Patient Health Questionnaire. We identified 522 people with new-onset PTSD, 151 with anxiety, and 303 with depression following deployment. In adjusted models, combat-related trauma and predeployment insomnia symptoms were significantly associated with higher odds of developing posttraumatic stress disorder, depression, and anxiety postdeployment. CONCLUSIONS: Sleep characteristics, especially insomnia symptoms, are related to the development of mental disorders following military deployments. Assessment of insomnia symptoms predeployment may help to better identify those at highest risk for subsequent adverse mental health outcomes. CITATION: Gehrman P; Seelig AD; Jacobson IG; Boyko EJ; Hooper TI; Gackstetter GD; Ulmer CS; Smith TC; for the Millennium Cohort Study Team. Predeployment sleep duration and insomnia symptoms as risk factors for new-onset mental health disorders following military deployment. SLEEP 2013;36(7):1009-1018.