A Functional Adenosine Deaminase Polymorphism Associates with Evening Melatonin Levels and Sleep Quality.

Increased adenosine levels throughout the day promote sleepiness. A single nucleotide polymorphism (SNP) in the adenosine deaminase ADA gene (rs73598374) has been shown to affect sleep regulation. The extent to which lower ADA enzymatic activity is associated with the homeostatic sleep factor, melatonin, is uncertain. To test this possibility, we assessed the relationship between the ADA polymorphism and evening melatonin levels, as well as self-reported sleep behavior. Given the close relationship between mood and sleep behavior, we further tested the impact of ADA genotype on self-reported mood. We show that relative to the GG homozygotes, the A allele carriers (higher adenosine levels) had significantly higher evening melatonin levels as well as significantly better sleep quality. We further show the correlations between sleep and mood measures were altered by ADA genotype, with a stronger relationship observed in the GG (lower adenosine) group. Combined, these findings advance our understanding of the biochemistry of melatonin production by showing that there is a relationship between ADA genotype and melatonin levels. The differential relationships between sleep and psychological health between the genotype groups may reveal novel insights about the development of genotype-specific progression of various psychological disorders such as chronic anxiety and stress.

A PER3 Polymorphism Interacts with Sleep Duration to Influence Transient Mood States in Women.

BACKGROUND: Expression of the clock family of genes in the suprachiasmatic nuclei (SCN) regulates the molecular control of circadian timing. Increasing evidence also implicates clock gene activity in the development of mood disorders. In particular, variation in the PER3 clock gene has been shown to influence diurnal preference and sleep homeostasis. However, there is not currently a clear association between PER3 polymorphisms and mood. This is possibly because the PER3 gene has been shown to influence homeostatic sleep drive, rather than circadian timing, and the PER3 gene may be behaviorally relevant only under chronic sleep loss conditions. METHODS: To test the association between PER3 allele status and impaired mood, a total of 205 healthy women were genotyped for PER3 allele status and responded to previously-validated psychological questionnaires surveying self-reported sleep habits (MEQ, PSQI) and mood. Our mood measures included two measures of short-term, transient mood (state anxiety and mood disturbance) and two measures of longer term, ongoing mood (trait anxiety and depressive symptomology). RESULTS: The PER3 genotype distribution was 88 (42.9%) for PER3(4/4), 98 (47.8%) for PER3(4/5), and 19 (9.3%) for PER3(5/5). Our sleep duration x genotype interaction analyses showed that, relative to longer allele carriers, PER3(4/4) genotypes were at greater risk for transient psychological effects (mood and state anxiety) when they reported reduced sleep durations. CONCLUSION: Sleep duration plays a critical role in understanding the extent to which PER3 allele status relates to mood states.

Poor sleep quality is associated with a negative cognitive bias and decreased sustained attention.

Poor sleep quality has been demonstrated to diminish cognitive performance, impair psychosocial functioning and alter the perception of stress. At present, however, there is little understanding of how sleep quality affects emotion processing. The aim of the present study was to determine the extent to which sleep quality, measured through the Pittsburg Sleep Quality Index, influences affective symptoms as well as the interaction between stress and performance on an emotional memory test and sustained attention task. To that end, 154 undergraduate students (mean age: 21.27 years, standard deviation = 4.03) completed a series of measures, including the Pittsburg Sleep Quality Index, the Sustained Attention to Response Task, an emotion picture recognition task and affective symptom questionnaires following either a control or physical stress manipulation, the cold pressor test. As sleep quality and psychosocial functioning differ among chronotypes, we also included chronotype and time of day as variables of interest to ensure that the effects of sleep quality on the emotional and non-emotional tasks were not attributed to these related factors. We found that poor sleep quality is related to greater depressive symptoms, anxiety and mood disturbances. While an overall relationship between global Pittsburg Sleep Quality Index score and emotion and attention measures was not supported, poor sleep quality, as an independent component, was associated with better memory for negative stimuli and a deficit in sustained attention to non-emotional stimuli. Importantly, these effects were not sensitive to stress, chronotype or time of day. Combined, these results suggest that individuals with poor sleep quality show an increase in affective symptomatology as well as a negative cognitive bias with a concomitant decrease in sustained attention to non-emotional stimuli.

Acute sleep deprivation disrupts emotion, cognition, inflammation, and cortisol in young healthy adults.

Chronic sleep deprivation has been demonstrated to diminish cognitive performance, alter mood states, and concomitantly dysregulate inflammation and stress hormones. At present, however, there is little understanding of how an acute sleep deprivation may collectively affect these factors and alter functioning. The present study aimed to determine the extent to which 24-h of sleep deprivation influences inflammatory cytokines, stress hormones, cognitive processing across domains, and emotion states. To that end, 23 participants (mean age = 20.78 years, SD = 2.87) filled out clinical health questionnaires measured by the Pittsburgh Sleep Quality Index, Morningness Eveningness Questionnaire, and Center for Epidemiological Studies Depression Scale. Actigraph was worn for seven days across testing to record sleep duration. At each session participants underwent a series of measures, including saliva and blood samples for quantification of leptin, ghrelin, IL-1ß, IL-6, CRP, and cortisol levels, they completed a cognitive battery using an iPad, and an emotion battery. We found that an acute sleep deprivation, limited to a 24 h period, increases negative emotion states such as anxiety, fatigue, confusion, and depression. In conjunction, sleep deprivation results in increased inflammation and decreased cortisol levels in the morning, that are accompanied by deficits in vigilance and impulsivity. Combined, these results suggest that individuals who undergo 24 h sleep deprivation will induce systemic alterations to inflammation and endocrine functioning, while concomitantly increasing negative emotions.

Catechol-O-methyltransferase Val158Met polymorphism associates with affect and cortisol levels in women.

Introduction: We tested the extent to which the catechol-O-methyltransferase (COMT) Val158Met polymorphism is associated with affective state and evening cortisol levels. We limited our study to women as previous research suggests that the link between COMT genotype and psychological health is entangled by sex differences. Materials and Methods: The participants were assessed on measures of anxiety, mood disturbance, depressive symptomatology, and perceived stress. We also evaluated participants on a quality of life measures that included two emotion domains and two physical domains (physical health and environment). Results: We found that under normal (nonstress) conditions, the COMT A allele (Met carriers, higher dopamine) associates with healthier affect and lower afternoon cortisol levels in women. These effects were limited to affective measures and not to physical or environmental quality of life. Conclusions: These findings help to shed light on the complex nature of COMT and emotion, and suggest that both sex and task condition (stress vs. nonstress) should be considered when examining the relationship between COMT genotype and emotion.

Changes in attention to an emotional task after sleep deprivation: neurophysiological and behavioral findings.

While sleep loss is shown to have widespread effects on cognitive processes, little is known about the impact of sleep loss on emotion processes. In order to expand on previous behavioral and physiological findings on how sleep loss influences emotion processing, we administered positive, negative, and neutral affective visual stimuli to individuals after one night of sleep deprivation while simultaneously acquiring EEG event related potential (ERP) data and recording affective behavioral responses. We compared these responses to a baseline testing session. We specifically looked at the late positive potential (LPP) component of the visual ERP as an established sensitive measure of attention to emotionally-charged visual stimuli. Our results show that after sleep deprivation, the LPP no longer discriminates between emotional and non-emotional pictures; after sleep deprivation the LPP amplitude was of similar amplitude for neutral, positive, and negative pictures. This effect was driven by an increase in the LPP to neutral pictures. Our behavioral measures show that, relative to baseline testing, emotional pictures are rated as less emotional following sleep deprivation with a concomitant reduction in emotional picture-induced anxiety. We did not observe any change in cortisol concentrations after sleep deprivation before or after emotional picture exposure, suggesting that the observed changes in emotion processing are independent of potential stress effects of sleep deprivation. Combined, our findings suggest that sleep loss interferes with proper allocation of attention resources during an emotional task.

Sleep restriction and delayed sleep associate with psychological health and biomarkers of stress and inflammation in women.

STUDY OBJECTIVES: Despite strong associations between sleep duration and health, there is no clear understanding of how volitional chronic sleep restriction (CSR) alters the physiological processes that lead to poor health in women. We focused on biochemical and psychological factors that previous research suggests are essential to uncovering the role of sleep in health. DESIGN: Cross-sectional study. SETTING: University-based. PARTICIPANTS: Sixty female participants (mean age, 19.3; SD, 2.1 years). MEASUREMENTS: We analyzed the association between self-reported volitional CSR and time to go to sleep on a series of sleep and psychological health measures as well as biomarkers of immune functioning/inflammation (interleukin [IL]-1ß), stress (cortisol), and sleep regulation (melatonin). RESULTS: Across multiple measures, poor sleep was associated with decreased psychological health and a reduced perception of self-reported physical health. Volitional CSR was related to increased cortisol and increased IL-1ß levels. We separately looked at individuals who experienced CSR with and without delayed sleep time and found that IL-1ß levels were significantly elevated in CSR alone and in CSR combined with a late sleep time. Cortisol, however, was only elevated in those women who experienced CSR combined with a late sleep time. We did not observe any changes in melatonin across groups, and melatonin levels were not related to any sleep measures. CONCLUSIONS: New to our study is the demonstration of how an increase in a proinflammatory process and an increase in hypothalamic-pituitary-adrenal axis activity both relate to volitional CSR, with and without a delayed sleep time. We further show how these mechanisms relate back to psychological and self-reported health in young adult women.

REM sleep and the early development of posttraumatic stress disorder.

OBJECTIVE: The potential for chronicity and treatment resistance once posttraumatic stress disorder (PTSD) has become established has stimulated interest in understanding the early pathogenesis of the disorder. Arousal regulation and memory consolidation appear to be important in determining the development of PTSD; both are functions of sleep. Sleep findings from patients with chronic PTSD are complex and somewhat contradictory, and data from the acute phase are quite limited. The aim of the present study was to obtain polysomnographic recordings during an acute period after life-threatening experiences and injury and to relate measures of sleep duration and maintenance and the timing, intensity, and continuity of REM sleep to the early development of PTSD. METHOD: Twenty-one injured subjects meeting study criteria received at least one polysomnographic recording close to the time of medical/surgical stabilization and within a month of injury. PTSD symptoms were assessed concurrently and 6 weeks later. Sleep measures were compared among injured subjects with and without significant PTSD symptoms at follow-up and 10 noninjured comparison subjects and were also correlated with PTSD severity. RESULTS: There was more wake time after the onset of sleep in injured, trauma-exposed patients than in noninjured comparison subjects. Development of PTSD symptoms was associated with shorter average duration of REM sleep before a stage change and more periods of REM sleep. CONCLUSIONS: The development of PTSD symptoms after traumatic injury is associated with a more fragmented pattern of REM sleep.

Accuracy of sleep perceptions among insomnia sufferers and normal sleepers.

OBJECTIVE: To examine the distribution, consistency, and correlates of sleep time perceptions in primary insomnia sufferers and normal sleepers across settings (laboratory and home). METHODS: Fifty-two middle-aged and older insomnia sufferers and 49 matched normal sleepers underwent multiple nights of laboratory and home polysomnography (PSG) and provided concurrent subjective estimates of their sleep. Descriptive statistics, cluster analyses, and inferential tests were used to examine the nature of sleep time perceptions, identify subgroups with distinctive patterns such as perceptions, and explore factors that may contribute to these subgroups' distinctive sleep perceptions. RESULTS: Consistent with previous studies, the insomnia sufferers, as a group, showed a greater tendency to underestimate the time they slept than did the normal sleepers, but the accuracy of sleep time perceptions varied widely within each sample. Correlational analyses showed that study participants in each sample showed a moderate level of consistency in how accurately they estimated sleep time across nights. Subsequent cluster analyses conducted to identify subgroups with distinctive patterns of sleep time perceptions yielded four subgroups within the insomnia sample and three subgroups within the normal sleeper sample. Although the sleep setting significantly affected sleep perceptions for one insomnia subgroup, both laboratory and home objective-subjective sleep comparisons provided similar impressions regarding the relative accuracy of each subgroup's nocturnal sleep/wake perceptions. Finally, varying patterns of subgroup differences were noted across several common psychometric measures. CONCLUSIONS: The underestimation of sleep time is not a generic characteristic that separates all insomnia sufferers from normal sleepers. Sleep setting, personality traits, and perhaps constitutional factors appear to influence perceptions of sleep and wake time duration.