Genome-wide DNA methylation patterns associated with sleep and mental health in children: a population-based study

Background: DNA methylation (DNAm) has been implicated in the biology of sleep. Yet, how DNAm patterns across the genome relate to different sleep outcomes, and whether these associations overlap with mental health is currently unknown. Here, we investigated associations of DNAm with sleep and mental health in a pediatric population. Methods: This cross-sectional study included 465 10-year-old children (51.3% female) from the Generation R Study. Genome-wide DNAm levels were measured using the Illumina 450K array (peripheral blood). Sleep problems were assessed from self-report and mental health outcomes from maternal questionnaires. Wrist actigraphy was used in 188 11-year-old children to calculate sleep duration and midpoint sleep. Weighted gene co-expression network analysis was used to identify highly comethylated DNAm ‘modules’, which were tested for associations with sleep and mental health outcomes. Results: We identified 64 DNAm modules, one of which associated with sleep duration after covariate and multiple testing adjustment. This module included CpG sites spanning 9 genes on chromosome 17, including MAPT – a key regulator of Tau proteins in the brain involved in neuronal function – as well as genes previously implicated in sleep duration. Follow-up analyses suggested that DNAm variation in this region is under considerable genetic control and shows strong blood–brain concordance. DNAm modules associated with sleep did not overlap with those associated with mental health. Conclusions: We identified one DNAm region associated with sleep duration, including genes previously reported by recent GWAS studies. Further research is warranted to examine the functional role of this region and its longitudinal association with sleep

Adolescent Changes in the Homeostatic and Circadian Regulation of Sleep

Sleep deprivation among adolescents is epidemic. We argue that this sleep deprivation is due in part to pubertal changes in the homeostatic and circadian regulation of sleep. These changes promote a delayed sleep phase that is exacerbated by evening light exposure and incompatible with aspects of modern society, notably early school start times. In this review of human and animal literature, we demonstrate that delayed sleep phase during puberty is likely a common phenomenon in mammals, not specific to human adolescents, and we provide insight into the mechanisms underlying this phenomenon

Sex of College Students Moderates Associations among Bedtime, Time in Bed, and Circadian Phase Angle.

Sex differences in circadian rhythms have been reported with some conflicting results. The timing of sleep and length of time in bed have not been considered, however, in previous such studies. The current study has 3 major aims: (1) replicate previous studies in a large sample of young adults for sex differences in sleep patterns and dim light melatonin onset (DLMO) phase; (2) in a subsample constrained by matching across sex for bedtime and time in bed, confirm sex differences in DLMO and phase angle of DLMO to bedtime; (3) explore sex differences in the influence of sleep timing and length of time in bed on phase angle. A total of 356 first-year Brown University students (207 women) aged 17.7 to 21.4 years (mean = 18.8 years, SD = 0.4 years) were included in these analyses. Wake time was the only sleep variable that showed a sex difference. DLMO phase was earlier in women than men and phase angle wider in women than men. Shorter time in bed was associated with wider phase angle in women and men. In men, however, a 3-way interaction indicated that phase angles were influenced by both bedtime and time in bed; a complex interaction was not found for women. These analyses in a large sample of young adults on self-selected schedules confirm a sex difference in wake time, circadian phase, and the association between circadian phase and reported bedtime. A complex interaction with length of time in bed occurred for men but not women. We propose that these sex differences likely indicate fundamental differences in the biology of the sleep and circadian timing systems as well as in behavioral choices

A cross-cultural comparison of sleep duration between U.S. and Australian adolescents: the effect of school start time, parent-set bedtimes and extracurricular load

STUDY OBJECTIVE: To test whether sleep duration on school nights differs between adolescents in Australia and the U.S. and, if so, whether this difference is explained by cultural differences in school start time, parental involvement in setting bedtimes and extra-curricular commitments. PARTICIPANTS: 385 adolescents aged 13-18 years (M=15.57,SD=0.95; 60% male) from Australia and 302 adolescents aged 13-19 years (M=16.03, SD=1.19; 35% male) from the United States. METHODS: Adolescents completed the School Sleep Habits Survey during class time, followed by an 8-day Sleep Diary. RESULTS: After controlling for age and sex, Australian adolescents obtained an average of 47 minutes more sleep per school night than those in the U.S. Australian adolescents were more likely to have a parent-set bedtime (17.5% vs 6.8%), have a later school start time (8:32am vs 7:45am) and spend less time per day on extra-curricular commitments (1h37m vs 2h41m) than their U.S. peers. The mediating factors of parent-set bedtimes, later school start times, and less time spent on extra-curricular activities were significantly associated with more total sleep. CONCUSIONS: In addition to biological factors, extrinsic cultural factors significantly impact upon adolescent sleep. The present study highlights the importance of a cross-cultural, ecological approach and the impact of early school start times, lack of parental limit setting around bedtimes and extracurricular load in limiting adolescent sleep

Association between depressive symptoms and sleep neurophysiology in early adolescence

BACKGROUND: Depression is highly prevalent among adolescents, and depressive symptoms rise rapidly during early adolescence. Depression is often accompanied by subjective sleep complaints and alterations in sleep neurophysiology. In this study, we examine whether depressive symptoms, measured on a continuum, are associated with subjective and objective (sleep architecture and neurophysiology) measures of sleep in early adolescence. METHODS: High-density sleep EEG, actigraphy, and self-reported sleep were measured in 52 early adolescents (12.31 years; SD: 1.121; 25 female). Depressive symptoms were measured on a continuum using the Center for Epidemiological Studies Depression Scale (CES-D). The association between depressive symptoms and 2 weeks of actigraphy, self-reported sleep, sleep architecture, and sleep neurophysiology (slow wave activity and sigma power) was determined via multiple linear regression with factors age, sex, and pubertal status. RESULTS: Despite no association between polysomnography measures of sleep quality and depressive symptoms, individuals with more depressive symptoms manifested worse actigraphically measured sleep. Less sleep spindle activity, as reflected in nonrapid eye movement sleep sigma power, was associated with more depressive symptoms over a large cluster encompassing temporal, parietal, and occipital regions. Furthermore, worse subjectively reported sleep quality was also associated with less sigma power over these same areas. Puberty, age, and sex did not impact this association. CONCLUSIONS: Sleep spindles have been hypothesized to protect sleep against environmental disturbances. Thus, diminished spindle power may be a subtle sign of disrupted sleep and its association with depressive symptoms in early adolescence may signal vulnerability for depression