Naps not as effective as a night of sleep at dissipating sleep pressure.

The two-process model of sleep posits that two processes interact to regulate sleep and wake: a homeostatic (Process S) and a circadian process (Process C). Process S compensates for sleep loss by increasing sleep duration and intensity. Process C gates the timing of sleep/wake favouring sleep during the circadian night in humans. In this study, we examined whether taking six naps throughout a 24-hr period would result in the same amount of dissipation of homeostatic pressure at the end of the day as a night of sleep, when time in bed is equivalent. Data from 46 participants (10-23 years; mean = 14.5 [±â€…2.9]; 25 females) were analysed. Slow-wave energy, normalized to account for individual differences in slow-wave activity, was used as a measure of sleep homeostasis. In the nap condition, slow-wave energy of six naps distributed equally during a 24-hr period was calculated. In the baseline condition, slow-wave energy was measured after 9-hr time in bed. A paired t-test was used to compare nap and baseline conditions. A linear regression was used to examine whether slow-wave energy varied as a function of age. Slow-wave energy was greater during baseline than the nap condition (p < .001). No association between age and slow-wave energy was found for baseline or nap conditions. Our findings indicate that multiple naps throughout the day are not as effective at dissipating sleep pressure as a night of sleep. This is likely due to the influence of the circadian system, which staves off sleep during certain times of the day.

The Influence of Circadian Timing on Olfactory Sensitivity.

Olfactory sensitivity has traditionally been viewed as a trait that varies according to individual differences but is not expected to change with one's momentary state. Recent research has begun to challenge this position and time of day has been shown to alter detection levels. Links between obesity and the timing of food intake further raise the issue of whether odor detection may vary as a function of circadian processes. To investigate this question, 37 (21 male) adolescents (M age = 13.7 years) took part in a 28-h forced desynchrony (FD) protocol with 17.5 h awake and 10.5 h of sleep, for 7 FD cycles. Odor threshold was measured using Sniffin' Sticks 6 times for each FD cycle (total threshold tests = 42). Circadian phase was determined by intrinsic period derived from dim light melatonin onsets. Odor threshold showed a significant effect of circadian phase, with lowest threshold occurring on average slightly after the onset of melatonin production, or about 1.5○ (approximately 21:08 h). Considerable individual variability was observed, however, peak olfactory acuity never occurred between 80.5○ and 197.5○ (~02:22-10:10 h). These data are the first to show that odor threshold is differentially and consistently influenced by circadian timing, and is not a stable trait. Potential biological relevance for connections between circadian phase and olfactory sensitivity are discussed.

An approach to understanding sleep and depressed mood in adolescents: person-centred sleep classification.

Depressive mood in youth has been associated with distinct sleep dimensions, such as timing, duration and quality. To identify discrete sleep phenotypes, we applied person-centred analysis (latent class mixture models) based on self-reported sleep patterns and quality, and examined associations between phenotypes and mood in high-school seniors. Students (n = 1451; mean age = 18.4 ± 0.3 years; 648 M) completed a survey near the end of high-school. Indicators used for classification included school night bed- and rise-times, differences between non-school night and school night bed- and rise-times, sleep-onset latency, number of awakenings, naps, and sleep quality and disturbance. Mood was measured using the total score on the Center for Epidemiologic Studies-Depression Scale. One-way anova tested differences between phenotype for mood. Fit indexes were split between 3-, 4- and 5-phenotype solutions. For all solutions, between phenotype differences were shown for all indicators: bedtime showed the largest difference; thus, classes were labelled from earliest to latest bedtime as 'A' (n = 751), 'B' (n = 428) and 'C' (n = 272) in the 3-class solution. Class B showed the lowest sleep disturbances and remained stable, whereas classes C and A each split in the 4- and 5-class solutions, respectively. Associations with mood were consistent, albeit small, with class B showing the lowest scores. Person-centred analysis identified sleep phenotypes that differed in mood, such that those with the fewest depressive symptoms had moderate sleep timing, shorter sleep-onset latencies and fewer arousals. Sleep characteristics in these groups may add to our understanding of how sleep and depressed mood associate in teens.

Individual differences in self-reported difficulty sleeping across the menstrual cycle.

The effect of menstrual cycle phase on sleep has been studied for decades; however, individual differences in the associations between sleep and menstrual phase have not been well studied. In addition, the associations between changes in sleep and other physiological and psychological factors that vary as a function of menstrual phase have not been thoroughly assessed. This study explored individual differences in daily self-reports of difficulty sleeping across the menstrual cycle, as well as associations between daily changes in difficulty sleeping and psychological/vegetative and somatic symptoms. Participants (n = 213 females, mean age = 21.29 ± 4.01 years) completed daily online questionnaires assessing` sleep, psychological and physical symptoms for two menstrual cycles. Two patterns of menstrual cycle-related self-reported difficulty sleeping emerged in addition to women who showed no cyclical change in self-reported difficulty sleeping: a perimenstrual increase and a mid-cycle increase. All psychological/vegetative symptoms and some of the somatic symptoms showed significant associations with self-reported difficulty sleeping. These findings highlight the importance of examining individual differences in sleep across the menstrual cycle and the significant contribution of a wide range of menstrual cycle-related psychological/vegetative and somatic symptoms.

Estimating sleep from multisensory armband measurements: validity and reliability in teens.

Given the recognition that sleep may influence obesity risk, there is increasing interest in measuring sleep parameters within obesity studies. The goal of the current analyses was to determine whether the SenseWear(®) Pro3 Armband (armband), typically used to assess physical activity, is reliable at assessing sleep parameters. The armband was compared with the AMI Motionlogger(®) (actigraph), a validated activity monitor for sleep assessment, and with polysomnography, the gold standard for assessing sleep. Participants were 20 adolescents (mean age = 15.5 years) with a mean body mass index percentile of 63.7. All participants wore the armband and actigraph on their non-dominant arm while in-lab during a nocturnal polysomnographic recording (600 min). Epoch-by-epoch sleep/wake data and concordance of sleep parameters were examined. No significant sleep parameter differences were found between the armband and polysomnography; the actigraph tended to overestimate sleep and underestimate wake compared with polysomnography. Both devices showed high sleep sensitivity, but lower wake detection rates. Bland-Altman plots showed large individual differences in armband sleep parameter concordance rates. The armband did well estimating sleep overall, with group results more similar to polysomnography than the actigraph; however, the armband was less accurate at an individual level than the actigraph.

What Role Does Sleep Play in Weight Gain in the First Semester of University?

We hypothesized that shorter sleep durations and greater variability in sleep patterns are associated with weight gain in the first semester of university. Students (N = 132) completed daily sleep diaries for 9 weeks, completed the MEQ (chronotype) and CES-D (depressed mood) at week 9, and self-reported weight/height (weeks 1 & 9). Mean and variability scores were calculated for sleep duration (TST, TSTv), bedtime (BT, BTv), and wake time (WT, WTv). An initial hierarchical regression evaluated (block 1) sex, ethnicity; (block 2) depressed mood, chronotype; (block 3) TST; (block 4) BT, WT; and (block 5; R(2) change = 0.09, p = 0.005) TSTv, BTv, WTv with weight change. A sex-by-TSTv interaction was found. A final model showed that ethnicity, TST, TSTv, and BTv accounted for 31% of the variance in weight change for males; TSTv was the most significant contributor (R(2) change = 0.21, p < 0.001). Daily variability in sleep duration contributes to males' weight gain. Further investigation needs to examine sex-specific outcomes for sleep and weight.

Acute Changes in Sleep Duration on Eating Behaviors and Appetite-Regulating Hormones in Overweight/Obese Adults.

There is considerable interest in the role of sleep in weight regulation, yet few studies have examined this relationship in overweight/obese (OW/OB) adults. Using a within-subject, counterbalanced design, 12 OW/OB women were studied in lab with two nights of short (5 hr time in bed [TIB]) and two nights of long (9 hr TIB) sleep. Hunger, consumption at a buffet, and fasting hormone levels were obtained. Significant polysomnographic differences occurred between conditions in total sleep time and sleep architecture (ps < .001). Percent energy from protein at the buffet increased following short sleep. No differences were observed for total energy intake or measured hormones. Further research is needed to determine how lengthening sleep impacts weight regulation in OW/OB adults.

Does sleep link child maltreatment to depressive symptoms among incoming first-year college students?

Study Objectives: We examined whether sleep (i.e. quality, regularity, and duration) mediated associations between child maltreatment (CM) and depressive symptoms among emerging adults undergoing the major life transition of starting college. Methods: Students (N = 1400; 44% male; 48% non-Hispanic white, 20% non-Hispanic Asian, 15% Hispanic all races, 7% non-Hispanic black, and 10% non-Hispanic other races) completed daily sleep diaries for 9 weeks, followed by the Childhood Trauma Questionnaire-Short Form, Pittsburgh Sleep Quality Index, and the Center for Epidemiologic Studies Depression Scale (CES-D). DSD data were used to compute participants' Sleep Regularity Index and average 24-hour total sleep time. We used a nonparametric structural equation modeling bootstrap approach and full information maximum likelihood to account for missing data. In model 1, we controlled for sex and race and ethnicity. In model 2, we further adjusted for baseline CES-D scores. Results: The prevalence of self-reported moderate-to-severe CM was 22%. Small but significant indirect effects of CM on greater depressive symptoms through worse sleep quality (ß = 0.06, 95% CI = 0.04, 0.09) and lower sleep regularity (ß = 0.02, 95% CI = 0.005, 0.03) were observed in model 1. In model 2, only the indirect effect of sleep quality remained significant (ß = 0.03, 95% CI = 0.01, 0.06). Conclusions: Poorer sleep quality may partially account for associations between CM and depressive symptoms during the first semester of college. Including sleep as a target in student health interventions on college campuses may not only help buffer against poor mental health outcomes for students with CM, but also poor academic and socioeconomic outcomes long-term.

A pilot study of light exposure as a countermeasure for menstrual phase-dependent neurobehavioral performance impairment in women.

OBJECTIVE: To examine effects of menstrual phase and nighttime light exposure on subjective sleepiness and auditory Psychomotor Vigilance Task performance. METHODS: Twenty-nine premenopausal women (12 =Follicular; 17 =Luteal) completed a 6.5-hour nighttime monochromatic light exposure with varying wavelengths (420-620 nm) and irradiances (1.03-14.12 µW/cm2). Subjective sleepiness, reaction time, and attentional lapses were compared between menstrual phases in women with minimal (<33%) or substantial (≥33%) light-induced melatonin suppression. RESULTS: When melatonin was not suppressed, women in the follicular phase had significantly worse reaction time (mean difference=145.1 ms, 95% CI 51.8-238.3, p < .001, Cohen's D=1.9) and lapses (mean difference=12.9 lapses, 95% CI 4.37-21.41, p < .001, Cohen's D=1.7) compared to women in the luteal phase. When melatonin was suppressed, women in the follicular phase had significantly better reaction time (mean difference=152.1 ms, 95% CI 43.88-260.3, p < .001, Cohen's D=1.7) and lapses (mean difference=12.3 lapses, 95% CI 1.14-25.6, p < .01, Cohen's D=1.6) compared to when melatonin was not suppressed, such that their performance was not different (p > .9) from women in the luteal phase. Subjective sleepiness did not differ by menstrual phase (mean difference=0.6, p > .08) or melatonin suppression (mean difference=0.2, p > .4). CONCLUSIONS: Nighttime light exposure sufficient to suppress melatonin can also mitigate neurobehavioral performance deficits associated with the follicular phase. Despite the relatively small sample size, these data suggest that nighttime light may be a valuable strategy to help reduce errors and accidents in female shift workers.

Melanopsin and rod-cone photoreceptors play different roles in mediating pupillary light responses during exposure to continuous light in humans.

In mammals, the pupillary light reflex is mediated by intrinsically photosensitive melanopsin-containing retinal ganglion cells that also receive input from rod-cone photoreceptors. To assess the relative contribution of melanopsin and rod-cone photoreceptors to the pupillary light reflex in humans, we compared pupillary light responses in normally sighted individuals (n = 24) with a blind individual lacking rod-cone function. Here, we show that visual photoreceptors are required for normal pupillary responses to continuous light exposure at low irradiance levels, and for sustained pupillary constriction during exposure to light in the long-wavelength portion of the visual spectrum. In the absence of rod-cone function, pupillomotor responses are slow and sustained, and cannot track intermittent light stimuli, suggesting that rods/cones are required for encoding fast modulations in light intensity. In sighted individuals, pupillary constriction decreased monotonically for at least 30 min during exposure to continuous low-irradiance light, indicating that steady-state pupillary responses are an order of magnitude slower than previously reported. Exposure to low-irradiance intermittent green light (543 nm; 0.1-4 Hz) for 30 min, which was given to activate cone photoreceptors repeatedly, elicited sustained pupillary constriction responses that were more than twice as great compared with exposure to continuous green light. Our findings demonstrate nonredundant roles for rod-cone photoreceptors and melanopsin in mediating pupillary responses to continuous light. Moreover, our results suggest that it might be possible to enhance nonvisual light responses to low-irradiance exposures by using intermittent light to activate cone photoreceptors repeatedly in humans.

Adolescence and parental history of alcoholism: insights from the sleep EEG.

BACKGROUND: Disrupted sleep is a common complaint of individuals with alcohol use disorder and in abstinent alcoholics. Furthermore, among recovering alcoholics, poor sleep predicts relapse to drinking. Whether disrupted sleep in these populations results from prolonged alcohol use or precedes the onset of drinking is not known. The aim of this study was to examine the sleep electroencephalogram (EEG) in alcohol-naïve, parental history positive (PH+), and negative (PH-) boys and girls. METHODS: All-night sleep EEG recordings in 2 longitudinal cohorts (child and teen) followed at 1.5 to 3 year intervals were analyzed. The child and teen participants were 9/10 and 15/16 years old at the initial assessment, respectively. Parental history status was classified by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria applied to structured interviews (DIS-IV) resulting in 14 PH- and 10 PH+ children and 14 PH- and 10 PH+ teens. Sleep data were visually scored in 30-second epochs using standard criteria. Power spectra were calculated for EEG derivations C3/A2, C4/A1, O2/A1, O1/A2 for nonrapid eye movement (NREM) and rapid eye movement (REM) sleep. RESULTS: We found no difference between PH+ and PH- individuals in either cohort for any visually scored sleep stage variable. Spectral power declined in both cohorts across assessments for NREM and REM sleep in all derivations and across frequencies independent of parental history status. With regard to parental history, NREM sleep EEG power was lower for the delta band in PH+ teens at both assessments for the central derivations. Furthermore, power in the sigma band for the right occipital derivation in both NREM and REM sleep was lower in PH+ children only at the initial assessment. CONCLUSIONS: We found no gross signs of sleep disruption as a function of parental history. Modest differences in spectral EEG power between PH+ and PH- children and teens indicate that a marker of parental alcohol history may be detectable in teens at risk for problem drinking.

Sleep regularity and body mass index: findings from a prospective study of first-year college students.

STUDY OBJECTIVES: Using data from a large, prospective study of sleep in first-year college students, we examined whether students' sleep regularity is associated with body mass index (BMI) and BMI change (∆BMI) during their first college semester. In a subset of participants, we also tested whether dim light melatonin onset (DLMO) phase and DLMO-bedtime phase angle are associated with BMI and ∆BMI. METHODS: Analyses included data from 581 students (mean age = 18.7 ± 0.5 years; 58% female; 48% non-white) who had their height and weight assessed at the start of classes (T1) and end of 9 weeks. Participants completed online daily sleep diaries from which total sleep time (TST) and the sleep regularity index (SRI) were calculated. Among participants who completed a DLMO protocol (n = 161), circadian phase was quantified by DLMO and circadian alignment by DLMO-bedtime phase angle. Data were analyzed with linear regressions that controlled for sex and average TST. RESULTS: Average SRI was 74.1 ± 8.7 (range: 25.7; 91.6). Average BMI at T1 was 22.0 ± 3.5 and participants gained 1.8 ± 2.4 kg (range: -7.2; 11.4); 39% gained 2-5 kg, 8% gained >5 kg. Lower SRI was associated with greater BMI at T1 (B = -0.06 [95% CI: -0.09; -0.02], p = 0.001) but not with ∆BMI (p = 0.062). Average TST was not significantly associated with BMI or ∆BMI, nor were circadian phase and alignment in the subsample (p's > 0.05). CONCLUSIONS: Sleep regularity is an understudied but relevant sleep dimension associated with BMI during young adulthood. Our findings warrant future work to examine longer-term associations between sleep regularity and weight gain.

Insights into smell and taste sensitivity in normal weight and overweight-obese adolescents.

Research examining connections between BMI and smell and taste sensitivity in adolescents has been minimal, methodologically inconsistent, and inconclusive. We sought to address this issue with an exploratory study of smell and taste sensitivity in overweight-obese (high BMI) and normal BMI male and female adolescents (ages 12-16 years), using previously validated chemosensory testing measures (Sniffin' Sticks, Taste Strips, 6-n-propylthiouracil: PROP), and taking pubertal stage into account. Puberty was evaluated with the validated Pubertal Development Scale and participants were then classified as either "early" or "late" pubertal stage. We used the phenylethyl alcohol (PEA) version of the Sniffin' Sticks olfactory threshold test and found that high BMI adolescents had significantly greater olfactory sensitivity than normal BMI adolescents. This observation contradicts previous results in overweight adults tested with the n-butanol version of Sniffin' Sticks. We also found that participants in early puberty had significantly higher olfactory sensitivity than participants in late puberty. No significant findings for taste sensitivity were obtained, though there is a suggestion that puberty may affect salty taste thresholds. Our results illuminate a potentially important difference in sensitivity to pure olfactory versus olfactory-trigeminal stimuli as a function of BMI, which the PEA and n-butanol versions of the Sniffin' Sticks respectively assess; and for the first time demonstrate variation in chemosensory acuity in relation to pubertal stage. These findings have implications for eating behavior during adolescence.

Chronotype Genetic Variant in PER2 is Associated with Intrinsic Circadian Period in Humans.

The PERIOD2 (PER2) gene is a core molecular component of the circadian clock and plays an important role in the generation and maintenance of daily rhythms. Rs35333999, a missense variant of PER2 common in European populations, has been shown to associate with later chronotype. Chronotype relates to the timing of biological and behavioral activities, including when we sleep, eat, and exercise, and later chronotype is associated with longer intrinsic circadian period (cycle length), a fundamental property of the circadian system. Thus, we tested whether this PER2 variant was associated with circadian period and found significant associations with longer intrinsic circadian period as measured under forced desynchrony protocols, the 'gold standard' for intrinsic circadian period assessment. Minor allele (T) carriers exhibited significantly longer circadian periods when determinations were based on either core body temperature or plasma melatonin measurements, as compared to non-carriers (by 12 and 11 min, respectively; accounting for ~7% of inter-individual variance). These findings provide a possible underlying biological mechanism for inter-individual differences in chronotype, and support the central role of PER2 in the human circadian timing system.

Reciprocal variations in sleep and drinking over time among heavy-drinking young adults.

Prior studies have established an association between sleep problems during early adolescence and heavy alcohol use/alcohol use disorder (AUD) risk in late adolescence. Less research has explored the association between sleep problems and heavy alcohol use during young adulthood, the period when AUD onset peaks. Moreover, research to date has primarily utilized cross-sectional, between-subjects' methods to examine this relationship, with limited focus on the potential intraindividual variation in these behaviors. Multilevel modeling techniques are well-suited to examine the variability in sleep problems and risky alcohol use over time and the dynamic bidirectional relations among these behaviors. This article reports on 42 heavy-drinking college students at-risk for an AUD based on their responses to a validated alcohol screener who completed daily diaries of sleep and alcohol use and wore a sleep-wake activity monitor (i.e., Philips Respironics Actiwatch 2™) daily for 7 days yielding a total of 294 reports. Hierarchical linear models demonstrated that days of heavy drinking predicted delayed bed and wake times within individuals and those individuals who tended to drink more heavily on average had shorter sleep durations. Conversely, days of shorter sleep duration, earlier wake times, and greater perceived sleep quality upon waking predicted greater alcohol use within individuals, and those who tended to feel more alert upon waking drank more on average. These results highlight important within- and between-person variability in the associations among objective and subjective sleep-related problems and at-risk drinking among young adults. Further, the results have implications for alcohol prevention/intervention strategies for young adults at risk for AUDs. (PsycINFO Database Record

Increased vulnerability to attentional failure during acute sleep deprivation in women depends on menstrual phase.

Study Objectives: To investigate sex differences in the effect of sleep deprivation on performance, accounting for menstrual phase in women. Methods: We examined alertness data from 124 healthy women and men (40 women, 84 men; aged 18-30 years) who maintained wakefulness for at least 30 hr in a laboratory setting using a constant routine protocol. Objective alertness was assessed every 2 hr using a 10 min psychomotor vigilance task. Subjective alertness was assessed every hour via the Karolinska Sleepiness Scale. Results: Women in the follicular phase of the menstrual cycle demonstrated the poorest level of performance. This poor performance was most pronounced at times corresponding to the typical sleep episode, demonstrating a window of vulnerability at night during this menstrual phase. At 24 hr awake, over 60 per cent of their responses were lapses of >500 ms and over one-third of their responses were longer lapses of at least 3 s in duration. Women in the luteal phase, however, were relatively protected from alertness failure, performing similar or better than both follicular-phase women and men. Conclusions: These results have important implications for education and intervention programs for shift workers, specifically during times of vulnerability to attentional failure that increase risk of injury.

The impact of sleep and psychiatric symptoms on alcohol consequences among young adults.

OBJECTIVE: Independent lines of research have documented links between psychiatric symptoms and poor sleep quality, psychiatric symptoms and alcohol use, and alcohol use and poor sleep quality. The current study examined the synergistic effect of poor sleep quality and psychiatric symptoms on alcohol-related consequences in heavy-drinking young adults. METHOD: Matriculating college students reporting at least one heavy drinking episode over the first nine weeks of the semester (N=385, 52% female) were categorized as experiencing 'good' (n=280) versus 'poor' sleep quality (n=105) and screening 'positive' (n=203) or 'negative' (n=182) for a psychiatric disorder. Sleep quality was assessed using the Pittsburgh Sleep Quality Index; psychiatric diagnosis was assessed using the Psychiatric Diagnostic Screening Questionnaire; and alcohol-related consequences were assessed using the Brief Young Adult Alcohol Consequences Questionnaire. General linear models were used to examine the main effects and interaction between sleep quality and psychiatric symptoms on alcohol-related consequences. RESULTS: Sleep quality moderated the association between psychiatric screen and alcohol-related consequences among heavy-drinking college students, such that psychiatric symptoms were associated with more alcohol-related consequences in the context of poor sleep quality. CONCLUSIONS: The combination of poor sleep quality and psychiatric symptoms is associated with increased alcohol-related consequences among heavy-drinking college students. Given the significant interaction between these symptoms, healthcare providers are encouraged to screen for the presence of sleep and psychiatric disorders among heavy-drinking young adults and to provide empirically-supported treatments as appropriate.

Current Alcohol Use is Associated with Sleep Patterns in First-Year College Students.

STUDY OBJECTIVES: To examine whether differences exist in self-reported sleep patterns and self-reported alcohol use for first-semester college students who do or do not report drinking during the last 6 months (mo) of high school. METHODS: Participants were 878 first-year college students. Students completed a survey in late May/early June about alcohol use and consequences, during the last 6 mo of high school; they later completed a daily record of sleep behavior and alcohol use across the first 9 weeks of the first semester of college. High school drinking status (past 6 mo) was classified as positive (HS-6 mo+) or negative (HS-6mo-) based on any indication of drinking on the May/June survey. Collegiate drinking was determined from first-semester daily diary alcohol reports as non-drinkers (0 reported drinks), drinkers (one or fewer heavy episodic drinking episodes (HED)), and drinkers reporting more than one HED episode. Sleep patterns were compared for non-drinkers, drinkers, and HED with no high school drinking history (HS-6mo-/HED). In addition, a separate analysis compared sleep patterns for college HED with (HS-6mo+/HED) and without (HS-6mo-/HED) high school self-reported alcohol use. RESULTS: Increased alcohol consumption in the first semester of college was associated with later bedtimes and rise times. We found no association of high school alcohol use and sleep in those with collegiate HED. CONCLUSIONS: Later sleep timing in those with greater alcohol use, supports a connection between sleep patterns and alcohol use. Such an early appearance of this connection may herald the development of alcohol use disorder in some individuals.

Circadian gene variants influence sleep and the sleep electroencephalogram in humans.

The sleep electroencephalogram (EEG) is highly heritable in humans and yet little is known about the genetic basis of inter-individual differences in sleep architecture. The aim of this study was to identify associations between candidate circadian gene variants and the polysomnogram, recorded under highly controlled laboratory conditions during a baseline, overnight, 8 h sleep opportunity. A candidate gene approach was employed to analyze single-nucleotide polymorphisms from five circadian-related genes in a two-phase analysis of 84 healthy young adults (28 F; 23.21 ± 2.97 years) of European ancestry. A common variant in Period2 (PER2) was associated with 20 min less slow-wave sleep (SWS) in carriers of the minor allele than in noncarriers, representing a 22% reduction in SWS duration. Moreover, spectral analysis in a subset of participants (n = 37) showed the same PER2 polymorphism was associated with reduced EEG power density in the low delta range (0.25-1.0 Hz) during non-REM sleep and lower slow-wave activity (0.75-4.5 Hz) in the early part of the sleep episode. These results indicate the involvement of PER2 in the homeostatic process of sleep. Additionally, a rare variant in Melatonin Receptor 1B was associated with longer REM sleep latency, with minor allele carriers exhibiting an average of 65 min (87%) longer latency from sleep onset to REM sleep, compared to noncarriers. These findings suggest that circadian-related genes can modulate sleep architecture and the sleep EEG, including specific parameters previously implicated in the homeostatic regulation of sleep.

Impact of Common Diabetes Risk Variant in MTNR1B on Sleep, Circadian, and Melatonin Physiology.

The risk of type 2 diabetes (T2D) is increased by abnormalities in sleep quantity and quality, circadian alignment, and melatonin regulation. A common genetic variant in a receptor for the circadian-regulated hormone melatonin (MTNR1B) is associated with increased fasting blood glucose and risk of T2D, but whether sleep or circadian disruption mediates this risk is unknown. We aimed to test if MTNR1B diabetes risk variant rs10830963 associates with measures of sleep or circadian physiology in intensive in-laboratory protocols (n = 58-96) or cross-sectional studies with sleep quantity and quality and timing measures from self-report (n = 4,307-10,332), actigraphy (n = 1,513), or polysomnography (n = 3,021). In the in-laboratory studies, we found a significant association with a substantially longer duration of elevated melatonin levels (41 min) and delayed circadian phase of dim-light melatonin offset (1.37 h), partially mediated through delayed offset of melatonin synthesis. Furthermore, increased T2D risk in MTNR1B risk allele carriers was more pronounced in early risers versus late risers as determined by 7 days of actigraphy. Our results provide the surprising insight that the MTNR1B risk allele influences dynamics of melatonin secretion, generating a novel hypothesis that the MTNR1B risk allele may extend the duration of endogenous melatonin production later into the morning and that early waking may magnify the diabetes risk conferred by the risk allele.