The impact of Mendelian sleep and circadian genetic variants in a population setting.

Rare variants in ten genes have been reported to cause Mendelian sleep conditions characterised by extreme sleep duration or timing. These include familial natural short sleep (ADRB1, DEC2/BHLHE41, GRM1 and NPSR1), advanced sleep phase (PER2, PER3, CRY2, CSNK1D and TIMELESS) and delayed sleep phase (CRY1). The association of variants in these genes with extreme sleep conditions were usually based on clinically ascertained families, and their effects when identified in the population are unknown. We aimed to determine the effects of these variants on sleep traits in large population-based cohorts. We performed genetic association analysis of variants previously reported to be causal for Mendelian sleep and circadian conditions. Analyses were performed using 191,929 individuals with data on sleep and whole-exome or genome-sequence data from 4 population-based studies: UK Biobank, FINRISK, Health-2000-2001, and the Multi-Ethnic Study of Atherosclerosis (MESA). We identified sleep disorders from self-report, hospital and primary care data. We estimated sleep duration and timing measures from self-report and accelerometery data. We identified carriers for 10 out of 12 previously reported pathogenic variants for 8 of the 10 genes. They ranged in frequency from 1 individual with the variant in CSNK1D to 1,574 individuals with a reported variant in the PER3 gene in the UK Biobank. No carriers for variants reported in NPSR1 or PER2 were identified. We found no association between variants analyzed and extreme sleep or circadian phenotypes. Using sleep timing as a proxy measure for sleep phase, only PER3 and CRY1 variants demonstrated association with earlier and later sleep timing, respectively; however, the magnitude of effect was smaller than previously reported (sleep midpoint ~7 mins earlier and ~5 mins later, respectively). We also performed burden tests of protein truncating (PTVs) or rare missense variants for the 10 genes. Only PTVs in PER2 and PER3 were associated with a relevant trait (for example, 64 individuals with a PTV in PER2 had an odds ratio of 4.4 for being "definitely a morning person", P = 4x10-8; and had a 57-minute earlier midpoint sleep, P = 5x10-7). Our results indicate that previously reported variants for Mendelian sleep and circadian conditions are often not highly penetrant when ascertained incidentally from the general population.

Associations between obesity, a composite risk score for probable long COVID, and sleep problems in SARS-CoV-2 vaccinated individuals.

BACKGROUND: Preliminary data suggests that obesity might hasten the decline in mRNA vaccine-induced immunity against SARS-CoV-2. However, whether this renders individuals with obesity more susceptible to long COVID symptoms post-vaccination remains uncertain. Given sleep's critical role in immunity, exploring the associations between obesity, probable long COVID symptoms, and sleep disturbances is essential. METHODS: We analyzed data from a survey of 5919 adults aged 18 to 89, all of whom received two SARS-CoV-2 mRNA vaccinations. Participants were categorized into normal weight, overweight, and obesity groups based on ethnicity-specific BMI cutoffs. The probability of long COVID was evaluated using the Post-Acute Sequelae of SARS-CoV-2 (PASC) score, as our survey did not permit confirmation of acute SARS-CoV-2 infection through methods such as antibody testing. Additionally, sleep patterns were assessed through questionnaires. RESULTS: Participants with obesity exhibited a significantly higher adjusted odds ratio (OR) of having a PASC score of 12 or higher, indicative of probable long COVID in our study, compared to those with normal weight (OR: 1.55, 95% CI: 1.05, 2.28). No significant difference was observed for overweight individuals (OR: 0.92 [95% CI: 0.63, 1.33]). Both obesity and probable long COVID were associated with increased odds of experiencing a heightened sleep burden, such as the presence of obstructive sleep apnea or insomnia (P < 0.001). However, no significant interaction between BMI and probable long COVID status was found. CONCLUSIONS: Even post-vaccination, individuals with obesity may encounter a heightened risk of experiencing prolonged COVID-19 symptoms. However, confirming our observations necessitates comprehensive studies incorporating rigorous COVID infection testing, such as antibody assays - unavailable in our anonymous survey. Additionally, it is noteworthy that the correlation between probable long COVID and sleep disturbances appears to be independent of BMI.

Comparison of actigraphy-measured and parent-reported sleep in association with weight status among preschool children.

This study compared weekday and weekend actigraphy-measured and parent-reported sleep in relation to weight status among preschool-aged children. Participants were 3-6 years old preschoolers from the cross-sectional DAGIS-study with sleep data for ≥2 weekday and ≥2 weekend nights. Parents-reported sleep onset and wake-up times were gathered alongside 24 h hip-worn actigraphy. An unsupervised Hidden-Markov Model algorithm provided actigraphy-measured night time sleep without the guidance of reported sleep times. Waist-to-height ratio and age-and-sex-specific body mass index characterised weight status. Comparison of methods were assessed with consistency in quintile divisions and Spearman correlations. Associations between sleep and weight status were assessed with adjusted regression models. Participants included 638 children (49% girls) with a mean ± SD age of 4.76 ± 0.89. On weekdays, 98%-99% of actigraphy-measured and parent-reported sleep estimates were classified in the same or adjacent quintile and were strongly correlated (rs = 0.79-0.85, p < 0.001). On weekends, 84%-98% of actigraphy-measured and parent-reported sleep estimates were respectively classified and correlations were moderate to strong (rs = 0.62-0.86, p < 0.001). Compared with actigraphy-measured sleep, parent-reported sleep had consistently earlier onset, later wake-up, and greater duration. Earlier actigraphy-measured weekday sleep onset and midpoint were associated with a higher body mass index (respective ß-estimates: -0.63, p < 0.01 and -0.75, p < 0.01) and waist-to-height ratio (-0.004, p = 0.03 and -0.01, p = 0.02). Though the sleep estimation methods were consistent and correlated, actigraphy measures should be favoured as they are more objective and sensitive to identifying associations between sleep timing and weight status compared with parent reports.

Nightmare frequency is a risk factor for suicidal ideation during the COVID-19 pandemic.

The association between nightmare frequency (NMF) and suicidal ideation (SI) is well known, yet the impact of the COVID-19 pandemic on this relation is inconsistent. This study aimed to investigate changes in NMF, SI, and their association during the COVID-19 pandemic. Data were collected in 16 countries using a harmonised questionnaire. The sample included 9328 individuals (4848 women; age M[SD] = 46.85 [17.75] years), and 17.60% reported previous COVID-19. Overall, SI was significantly 2% lower during the pandemic vs. before, and this was consistent across genders and ages. Most countries/regions demonstrated decreases in SI during this pandemic, with Austria (-9.57%), Sweden (-6.18%), and Bulgaria (-5.14%) exhibiting significant declines in SI, but Italy (1.45%) and Portugal (2.45%) demonstrated non-significant increases. Suicidal ideation was more common in participants with long-COVID (21.10%) vs. short-COVID (12.40%), though SI did not vary by COVID-19 history. Nightmare frequency increased by 4.50% during the pandemic and was significantly higher in those with previous COVID-19 (14.50% vs. 10.70%), during infection (23.00% vs. 8.10%), and in those with long-COVID (18.00% vs. 8.50%). The relation between NMF and SI was not significantly stronger during the pandemic than prior (rs = 0.18 vs. 0.14; z = 2.80). Frequent nightmares during the pandemic increased the likelihood of reporting SI (OR = 1.57, 95% CI 1.20-2.05), while frequent dream recall during the pandemic served a protective effect (OR = 0.74, 95% CI 0.59-0.94). These findings have important implications for identifying those at risk of suicide and may offer a potential pathway for suicide prevention.

Association of the timing of evening eating with BMI Z-score and waist-to-height ratio among preschool-aged children in Finland.

Later timing of eating has been associated with higher adiposity among adults and children in several studies, but not all. Moreover, studies in younger children are scarce. Hence, this study investigated the associations of the timing of evening eating with BMI Z-score and waist-to-height ratio (WHtR), and whether these associations were moderated by chronotype among 627 preschoolers (3-6-year-olds) from the cross-sectional DAGIS survey in Finland. Food intake was measured with 3-d food records, and sleep was measured with hip-worn actigraphy. Three variables were formed to describe the timing of evening eating: (1) clock time of the last eating occasion (EO); (2) time between the last EO and sleep onset; and (3) percentage of total daily energy intake (%TDEI) consumed 2 h before sleep onset or later. Chronotype was assessed as a sleep debt-corrected midpoint of sleep on the weekend (actigraphy data). The data were analysed with adjusted linear mixed effects models. After adjusting for several confounders, the last EO occurring closer to sleep onset (estimate = -0·006, 95 % CI (-0·010, -0·001)) and higher %TDEI consumed before sleep onset (estimate = 0·0004, 95 % CI (0·00003, 0·0007)) were associated with higher WHtR. No associations with BMI Z-score were found after adjustments. Clock time of the last EO was not significantly associated with the outcomes, and no interactions with chronotype emerged. The results highlight the importance of studying the timing of eating relative to sleep timing instead of only as clock time.

The role of sleep and dreams in long-COVID.

Recent investigations show that many people affected by SARS-CoV2 (COVID-19) report persistent symptoms 2-3 months from the onset of the infection. Here, we report the Italian findings from the second International COVID-19 Sleep Study survey, aiming to investigate sleep and dream alterations in participants with post-acute symptoms, and identify the best determinants of these alterations among patients with long-COVID. Data from 383 participants who have had COVID-19 were collected through a web-survey (May-November 2021). Descriptive analyses were performed to outline the sociodemographic characteristics of long-COVID (N = 270, with at least two long-lasting symptoms) and short-COVID (N = 113, with none or one long-lasting symptom) participants. They were then compared concerning sleep and dream measures. We performed multiple linear regressions considering as dependent variables sleep and dream parameters discriminating the long-COVID group. Age, gender, work status, financial burden, COVID-19 severity and the level of care were significantly different between long-COVID and short-COVID subjects. The long-COVID group showed greater sleep alterations (sleep quality, daytime sleepiness, sleep inertia, naps, insomnia, sleep apnea, nightmares) compared with the short-COVID group. We also found that the number of long-COVID symptoms, psychological factors and age were the best explanatory variables of sleep and oneiric alterations. Our findings highlight that sleep alterations are part of the clinical presentation of the long-COVID syndrome. Moreover, psychological status and the number of post-acute symptoms should be considered as state-like variables modulating the sleep problems in long-COVID individuals. Finally, according to previous investigations, oneiric alterations are confirmed as a reliable mental health index.

Dream-enactment behaviours during the COVID-19 pandemic: an international COVID-19 sleep study.

There has been increasing concern about the long-term impact of coronavirus disease 2019 (COVID-19) as evidenced by anecdotal case reports of acute-onset parkinsonism and the polysomnographic feature of increased rapid eye movement sleep electromyographic activity. This study aimed to determine the prevalence and correlates of dream-enactment behaviours, a hallmark of rapid eye movement sleep behaviour disorder, which is a prodrome of α-synucleinopathy. This online survey was conducted between May and August 2020 in 15 countries/regions targeting adult participants (aged ≥18 years) from the general population with a harmonised structured questionnaire on sleep patterns and disorders, COVID-19 diagnosis and symptoms. We assessed dream-enactment behaviours using the Rapid Eye Movement Sleep Behaviour Disorder Single-Question Screen with an additional question on their frequency. Among 26,539 respondents, 21,870 (82.2%) answered all items that were analysed in this study (mean [SD] age 41.6 [15.8] years; female sex 65.5%). The weighted prevalence of lifetime and weekly dream-enactment behaviours was 19.4% and 3.1% and were found to be 1.8- and 2.9-times higher in COVID-19-positive cases, respectively. Both lifetime and weekly dream-enactment behaviours were associated with young age, male sex, smoking, alcohol consumption, higher physical activity level, nightmares, COVID-19 diagnosis, olfactory impairment, obstructive sleep apnea symptoms, mood, and post-traumatic stress disorder features. Among COVID-19-positive cases, weekly dream-enactment behaviours were positively associated with the severity of COVID-19. Dream-enactment behaviours are common among the general population during the COVID-19 pandemic and further increase among patients with COVID-19. Further studies are needed to investigate the potential neurodegenerative effect of COVID-19.

Sleep symptoms are essential features of long-COVID - Comparing healthy controls with COVID-19 cases of different severity in the international COVID sleep study (ICOSS-II).

Many people report suffering from post-acute sequelae of COVID-19 or "long-COVID", but there are still open questions on what actually constitutes long-COVID and how prevalent it is. The current definition of post-acute sequelae of COVID-19 is based on voting using the Delphi-method by the WHO post-COVID-19 working group. It emphasizes long-lasting fatigue, shortness of breath and cognitive dysfunction as the core symptoms of post-acute sequelae of COVID-19. In this international survey study consisting of 13,628 subjects aged 18-99 years from 16 countries of Asia, Europe, North America and South America (May-Dec 2021), we show that post-acute sequelae of COVID-19 symptoms were more prevalent amongst the more severe COVID-19 cases, i.e. those requiring hospitalisation for COVID-19. We also found that long-lasting sleep symptoms are at the core of post-acute sequelae of COVID-19 and associate with the COVID-19 severity when COVID-19 cases are compared with COVID-negative cases. Specifically, fatigue (61.3%), insomnia symptoms (49.6%) and excessive daytime sleepiness (35.8%) were highly prevalent amongst respondents reporting long-lasting symptoms after hospitalisation for COVID-19. Understanding the importance of sleep-related symptoms in post-acute sequelae of COVID-19 has a clinical relevance when diagnosing and treating long-COVID.

Associations between changes in habitual sleep duration and lower self-rated health among COVID-19 survivors: findings from a survey across 16 countries/regions.

BACKGROUND: Self-rated health (SRH) is widely recognized as a clinically significant predictor of subsequent mortality risk. Although COVID-19 may impair SRH, this relationship has not been extensively examined. The present study aimed to examine the correlation between habitual sleep duration, changes in sleep duration after infection, and SRH in subjects who have experienced SARS-CoV-2 infection. METHODS: Participants from 16 countries participated in the International COVID Sleep Study-II (ICOSS-II) online survey in 2021. A total of 10,794 of these participants were included in the analysis, including 1,509 COVID-19 individuals (who reported that they had tested positive for COVID-19). SRH was evaluated using a 0-100 linear visual analog scale. Habitual sleep durations of < 6 h and > 9 h were defined as short and long habitual sleep duration, respectively. Changes in habitual sleep duration after infection of ≤ -2 h and ≥ 1 h were defined as decreased or increased, respectively. RESULTS: Participants with COVID-19 had lower SRH scores than non-infected participants, and those with more severe COVID-19 had a tendency towards even lower SRH scores. In a multivariate regression analysis of participants who had experienced COVID-19, both decreased and increased habitual sleep duration after infection were significantly associated with lower SRH after controlling for sleep quality (ß = -0.056 and -0.058, respectively, both p < 0.05); however, associations between current short or long habitual sleep duration and SRH were negligible. Multinomial logistic regression analysis showed that decreased habitual sleep duration was significantly related to increased fatigue (odds ratio [OR] = 1.824, p < 0.01), shortness of breath (OR = 1.725, p < 0.05), diarrhea/nausea/vomiting (OR = 2.636, p < 0.01), and hallucinations (OR = 5.091, p < 0.05), while increased habitual sleep duration was significantly related to increased fatigue (OR = 1.900, p < 0.01). CONCLUSIONS: Changes in habitual sleep duration following SARS-CoV-2 infection were associated with lower SRH. Decreased or increased habitual sleep duration might have a bidirectional relation with post-COVID-19 symptoms. Further research is needed to better understand the mechanisms underlying these relationships for in order to improve SRH in individuals with COVID-19.

Late-Night Digital Media Use in Relation to Chronotype, Sleep and Tiredness on School Days in Adolescence.

Previous studies on late-night digital media use and adolescent sleep have not considered how chronotype, a natural tendency to be awake or asleep at certain time, is associated with this relationship. Therefore, the nature of the relationship between late-night digital media use and sleep in different chronotypes remains still unknown. The sample consisted of 15-20-year-old Finnish adolescents (n = 1084, mean age = 16.9 years, SD = 0.93, 45.7% female). This study examined whether chronotype, measured as diurnal type and midpoint of sleep, was associated with the time of evening/night when digital media was used. Associations between the use of different forms of digital media and sleep quality, sleep duration and tiredness on school days were also investigated. Finally, the mediation effect of late-night digital media use to the relationship between chronotype and sleep was examined. Generalized linear models showed that evening chronotype, weekend midpoint of sleep, and the time of evening or night at which digital media was used were associated with more insufficient sleep and tiredness, lower sleep quality and shorter sleep duration on school days. The total use of all media forms, i.e., late-night digital media for music, movies/series, social media, and studying, were associated with shorter sleep duration and more insufficient sleep and daytime tiredness. Late-night social media use also mediated the association between diurnal type and sleep quality. Watching movies or listening to music late at night was the strongest mediator of the association between diurnal type and sleep and tiredness. The most prominent finding shows that of the all different media forms, watching movies or listening to music late at night were associated with increased daytime tiredness, whereas late social media use was associated with poor sleep quality. These interactions were pronounced especially for evening-types. The findings of the current study suggest that the negative effects of late-night media use are reflected especially in sleep quality and daytime tiredness among evening-types during adolescence.

Disturbances in sleep, circadian rhythms and daytime functioning in relation to coronavirus infection and Long-COVID - A multinational ICOSS study.

This protocol paper describes the second survey produced by the International Covid Sleep Study (ICOSS) group with the aim to examine the associations between SARS-CoV-2 infection and sleep, sleepiness, and circadian problems as potential predisposing factors for more severe COVID-19 disease profile and for development of Long-COVID in the general population. The survey consists of 47 questions on sleep, daytime sleepiness, circadian rhythm, health, mental wellbeing, life habits, and socioeconomic situation before and during the pandemic, and conditional questions to those reporting having had coronavirus infection, being vaccinated, or suffering from particular sleep symptoms or sleep disorders. Surveys will be administered online between May and November 2021 in Austria, Brazil, Bulgaria, Canada, China, Croatia, Finland, France, Germany, Israel, Italy, Japan, Norway, Portugal, Sweden and USA. Data collected by the survey will give valuable information on the open questions regarding COVID-19 disease risk factors, symptomatology and evolution of Long-COVID, and on other long-term consequences related to the pandemic.

Eveningness increases risks for depressive and anxiety symptoms and hospital treatments mediated by insufficient sleep in a population-based study of 18,039 adults.

BACKGROUND: Epidemiological data show that having the eveningness associates with poor mental health. For preventive measures it is important to know which underlying factors mediate these associations and the burden posed to public health. This study examines at a population-based level, whether (1) circadian type and the sleep-wake behavior-based phase entrainment similarly associate with mental health problems, (2) there are differences in hospital treatments due to mental disorders between chronotypes, and (3) the association of chronotype with mental health is mediated by insufficient sleep. METHODS: The study sample (N = 18,039) consisted of population-based sample of Finnish adults, aged 25-74 years, with information on their circadian type and sleep patterns, mental health symptoms, and diagnosis as reported in a health examination survey, as well as hospital treatments as recorded on the national Hospital Discharge Register. RESULTS: All the mental health symptoms, diagnoses and hospital treatments were more pronounced among Evening-types, especially when assessed by circadian type. Insufficient sleep mediated most but not all of the associations between eveningness and mental health. CONCLUSIONS: Eveningness does not increase mental health risks only on symptom or diagnosis level, but also on hospital admission level. A higher prevalence of insufficient sleep among the Evening-types elevates the risk and severity for many of the mental health outcomes. Improving the sleep among Evening-types could help to improve their mental health prospective and ease the health care burden.

The association between high risk of sleep apnea, comorbidities, and risk of COVID-19: a population-based international harmonized study.

PURPOSE: Obstructive sleep apnea (OSA) may increase the risk of severe COVID-19; however, the level of potential modulation has not yet been established. The objective of the study was to determine the association between high risk of OSA, comorbidities, and increased risk for COVID-19, hospitalization, and intensive care unit (ICU) treatment. METHODS: We conducted a cross-sectional population-based web survey in adults in 14 countries/regions. The survey included sociodemographic variables and comorbidities. Participants were asked questions about COVID-19, hospitalization, and ICU treatment. Standardized questionnaire (STOP questionnaire for high risk of OSA) was included. Multivariable logistic regression was conducted adjusting for various factors. RESULTS: Out of 26,539 respondents, 20,598 (35.4% male) completed the survey. Mean age and BMI of participants were 41.5 ± 16.0 years and 24.0 ± 5.0 kg/m2, respectively. The prevalence of physician-diagnosed OSA was 4.1% and high risk of OSA was 9.5%. We found that high risk of OSA (adjusted odds ratio (aOR) 1.72, 95% confidence interval (CI): 1.20, 2.47) and diabetes (aOR 2.07, 95% CI: 1.23, 3.48) were associated with reporting of a COVID-19 diagnosis. High risk for OSA (aOR 2.11, 95% CI: 1.10-4.01), being male (aOR: 2.82, 95% CI: 1.55-5.12), having diabetes (aOR: 3.93, 95% CI: 1.70-9.12), and having depression (aOR: 2.33, 95% CI: 1.15-4.77) were associated with increased risk of hospitalization or ICU treatment. CONCLUSIONS: Participants at high risk of OSA had increased odds of having COVID-19 and were two times more likely to be hospitalized or treated in ICU.

Bidirectional Relationship of Sleep with Emotional and Behavioral Difficulties: A Five-year Follow-up of Finnish Adolescents.

The long-term effects of sleep on adolescent psychosocial well-being are mostly unknown, although insufficient sleep has been associated with emotional and behavioral difficulties in cross-sectional studies. With a five-year follow-up of Finnish adolescents (Time 1: n = 8834; Mean age = 13 years, 51.1% female, Time 2: n = 5315, Mean age = 15 years, 51.6% female, Time 3: n = 3712; Mean age = 17 years; 50.2% female), the purpose of this longitudinal study was to investigate the relations between self-reported sleep duration, sleep problems, and emotional and behavioral difficulties during adolescence. Emotional and behavioral difficulties were assessed using The Strengths and Difficulties Questionnaire (SDQ) measuring emotional symptoms, conduct problems, hyperactivity, peer problems and total difficulties. Sleep duration was calculated by counting the hours between self-reported bedtime and wake-up time. Sleep problems were assessed with a single question about the general sleep problems. According to the cross-lagged models for sleep and emotional and behavioral difficulties, the findings of this study indicate a developmental process during adolescence where, firstly, short sleep duration is a stronger predictor for current and prospective emotional and behavioral difficulties than vice versa. Secondly, increased emotional and behavioral difficulties expose adolescents to current and later sleep problems more strongly than reverse. Thus, the results show that short sleep duration predisposed to emotional and behavioral difficulties across adolescence, which then led to more prospective sleep problems. These findings suggest a developmental process where sleep and emotional and behavioral difficulties are intertwined in shaping adolescents' health.

Higher sleep spindle activity is associated with fewer false memories in adolescent girls.

BACKGROUND: Sleep facilitates the extraction of semantic regularities amongst newly encoded memories, which may also lead to increased false memories. We investigated sleep stage proportions and sleep spindles in the recollection of adolescents' false memories, and their potential sex-specific differences. METHODS: 196 adolescents (mean age 16.9 y; SD = 0.1, 61% girls) underwent the Deese, Roediger & McDermott (DRM) false memory procedure and overnight polysomnography, with free recall the following morning. Sleep was scored manually into stages 1, 2, 3 and REM. Stage 2 sleep spindle frequency, density, and peak amplitude were used as measures of spindle activity for slow (10-13 Hz) and fast (13-16 Hz) ranges. RESULTS: In girls, a lower number of critical lures was associated with higher spindle frequency (p ≤ 0.01), density (p ≤ 0.01), and amplitude (p = 0.03). Additionally, girls' longer sleep duration was associated with more intrusion words (p = 0.03), but not with critical lures. These associations survived adjustment for age, pubertal status, and intelligence. No significant results emerged in boys. CONCLUSIONS: In adolescent girls, higher spindle activity was associated with fewer critical lures being falsely recalled in the DRM paradigm. Unlike studies using adult participants, we did not observe any association between slow-wave sleep and false memory recollection.

ADHD symptoms are associated with decreased activity of fast sleep spindles and poorer procedural overnight learning during adolescence.

ADHD and its subclinical symptoms have been associated with both disturbed sleep and weakened overnight memory consolidation. As sleep spindle activity during NREM sleep plays a key role in both sleep maintenance and memory consolidation, we examined the association between subclinical ADHD symptoms and sleep spindle activity. Furthermore, we hypothesized that sleep spindle activity mediates the effect of ADHD symptoms on overnight learning outcome in a procedural memory task. We studied these questions in a community-based cohort of 170 adolescents (58% girls, mean age = 16.9, SD = 0.1 years), who filled in the Adult ADHD Self-Report Scale (ASRS-v1.1), and underwent an overnight sleep EEG coupled with a mirror tracing task before and after sleep. Elevated ADHD symptoms were associated with weaker fast sleep spindle activity, and poorer overnight learning in the procedural memory test. However, sleep spindles, contrary to the hypothesis, did not mediate the association between ADHD symptoms and overnight learning. Our results showed that a higher level of ADHD symptoms in adolescence is associated with similar alterations in sleep spindle activity as observed in many neuropsychiatric conditions and might contribute to altered synaptic connectivity and sleep fragmentation observed in ADHD.

Schizotypal traits are associated with sleep spindles and rapid eye movement in adolescence.

Research suggests an association between schizophrenia and a decrease in sleep spindle activity, as well as a change in sleep architecture. It is unknown how the continuum of psychotic symptoms relates to different features in the sleep electroencephalogram. We set out to examine how sleep architecture and stage 2 spindle activity are associated with schizotypy in a healthy adolescent population. The participants in our study (n = 176, 61% girls) came from a community-based cohort. Schizotypal traits were evaluated using the Schizotypal Personality Scale (STA) in early adolescence (mean age 12.3 years, SD = 0.5) and the participants underwent ambulatory overnight polysomnography at mean age 16.9 years (SD = 0.1). Sleep was scored in 30-s epochs into stages 1, 2, 3 and rapid eye movement (REM) sleep. Stage 2 spindles were detected using an automated algorithm. Spindle analyses from central and frontal derivations included spindle duration and density for slow (10-13 Hz) and fast (13-16 Hz) ranges. Covariates included sex and age. Those with the highest STA scores had a higher percentage of REM (B = 2.07 [95% CI, 0.17, 4.0]; p = .03) than those with the lowest scores. Those with the highest scores had shorter spindle duration, as derived from the frontal regions, and a slower oscillation range (B = -0.04 [95% CI, -0.07, -0.01]; p = .023) than those with the lowest scores. We conclude that high levels of schizotypy characteristics measured in early adolescence may be associated with distinguished features of sleep architecture, namely with spindle morphology and a higher proportion of REM sleep.

Genetic risk factors for schizophrenia associate with sleep spindle activity in healthy adolescents.

Schizophrenia has been associated with disturbed sleep, even before the onset of the disorder, and also in non-schizophrenic first-order relatives. This may point to an underlying genetic influence. Here we examine whether weighted polygenic risk scores (PRS) for schizophrenia are associated with sleep spindle activity in healthy adolescents. Our sample comes from a community-based cohort of 157 non-schizophrenic adolescents (57% girls) having both genetic data and an overnight sleep EEG measurement available. Based on a recent genome-wide association study, we calculated PRS for schizophrenia across the whole genome. We also calculated PRS for the CACNA1l gene region, which has been associated with both schizophrenia and sleep spindle formation. We performed an overnight sleep EEG at the homes of the participants. Stage two sleep spindles were detected using an automated algorithm. Sleep spindle amplitude, duration, intensity and density were measured separately for central and frontal derivations and for fast (13-16 Hz) and slow (10-13 Hz) spindles. PRS for schizophrenia was associated with higher fast spindle amplitude (p = 0.04), density (p = 0.006) and intensity (p = 0.04) at the central derivation, and PRS in the CACNA1l region associated with higher slow spindle amplitude (p = 0.01), duration (p = 0.03) and intensity (p = 0.002) at the central derivation. A positive association between genetic variants for schizophrenia and sleep spindle activity among healthy adolescents supports a view that sleep spindles and schizophrenia share similar genetic pathways. This study suggests that altered sleep spindle activity might serve as an endophenotype of schizophrenia.

Development of Late Circadian Preference: Sleep Timing From Childhood to Late Adolescence.

OBJECTIVES: To assess differences relating to circadian preference in objectively measured sleep patterns from childhood to adolescence over a 9-year period. We hypothesized there is developmental continuity in sleep timing and duration according to circadian preference. STUDY DESIGN: Young participants (N = 111, 65% girls) from a community-based birth cohort underwent sleep actigraphy at mean ages 8.1 (SD = 0.3), 12.3 (SD = 0.5), and 16.9 (SD = 0.1) years. A short version of Morningness-Eveningness Questionnaire was administered in late adolescence. At each follow-up, sleep midpoint, duration, wake after sleep onset, sleep efficiency, and weekend catch-up sleep were compared between those reporting morning, intermediate, and evening preferences in late adolescence. RESULTS: Mixed model analyses indicated that sleep timing was significantly earlier among morning types compared with evening types at all ages (P values < .04). The mean differences in sleep midpoint between morning and evening types increased from a mean of 19 minutes (age 8), 36 minutes (age 12), to 89 minutes (age 17). The largest change occurred from age 12 to 17 years. Sleep duration, wake after sleep onset, sleep efficiency, and catch-up sleep did not differ according to circadian preference. CONCLUSIONS: This study found significant continuity in sleep timing from childhood to adolescence over 9 years, indicating that late circadian preference reported in late adolescence begins to manifest in middle childhood. Further studies are needed to establish whether sleep timing has its origins at an even earlier age.

Outside-host phage therapy as a biological control against environmental infectious diseases.

BACKGROUND: Environmentally growing pathogens present an increasing threat for human health, wildlife and food production. Treating the hosts with antibiotics or parasitic bacteriophages fail to eliminate diseases that grow also in the outside-host environment. However, bacteriophages could be utilized to suppress the pathogen population sizes in the outside-host environment in order to prevent disease outbreaks. Here, we introduce a novel epidemiological model to assess how the phage infections of the bacterial pathogens affect epidemiological dynamics of the environmentally growing pathogens. We assess whether the phage therapy in the outside-host environment could be utilized as a biological control method against these diseases. We also consider how phage-resistant competitors affect the outcome, a common problem in phage therapy. The models give predictions for the scenarios where the outside-host phage therapy will work and where it will fail to control the disease. Parameterization of the model is based on the fish columnaris disease that causes significant economic losses to aquaculture worldwide. However, the model is also suitable for other environmentally growing bacterial diseases. RESULTS: Transmission rates of the phage determine the success of infectious disease control, with high-transmission phage enabling the recovery of the host population that would in the absence of the phage go asymptotically extinct due to the disease. In the presence of outside-host bacterial competition between the pathogen and phage-resistant strain, the trade-off between the pathogen infectivity and the phage resistance determines phage therapy outcome from stable coexistence to local host extinction. CONCLUSIONS: We propose that the success of phage therapy strongly depends on the underlying biology, such as the strength of trade-off between the pathogen infectivity and the phage-resistance, as well as on the rate that the phages infect the bacteria. Our results indicate that phage therapy can fail if there are phage-resistant bacteria and the trade-off between pathogen infectivity and phage resistance does not completely inhibit the pathogen infectivity. Also, the rate that the phages infect the bacteria should be sufficiently high for phage-therapy to succeed.