The interaction between polygenic risk and environmental influences: A direct test of the 3P model of insomnia in adolescents.

BACKGROUND: Stress is a universal phenomenon and one of the most common precipitants of insomnia. However, not everyone develops insomnia after experiencing a stressful life event. This study aims to test aspects of Spielman's '3P model of insomnia' (during adolescence) by exploring the extent to which: (a) insomnia symptoms are predicted by polygenic scores (PGS); (b) life events predict insomnia symptoms; (c) the interaction between PGS and life events contribute to the prediction of insomnia symptoms; (d) gene-environment interaction effects remain after controlling for sex. METHODS: The sample comprised 4,629 twins aged 16 from the Twin Early Development Study who reported on their insomnia symptoms and life events. PGS for insomnia were calculated. In order to test the main hypothesis of this study (a significant interaction between PGS and negative life events), we fitted a series of mixed effect regressions. RESULTS: The best fit was provided by the model including sex, PGS for insomnia, negative life events, and their interactions (AIC = 26,158.7). Our results show that the association between insomnia symptoms and negative life events is stronger for those with a higher genetic risk for insomnia. CONCLUSIONS: This work sheds light on the complex relationship between genetic and environmental factors implicated for insomnia. This study has tested for the first time the interaction between genetic predisposition (PGS) for insomnia and environmental stressors (negative life events) in adolescents. This work represents a direct test of components of Spielman's 3P model for insomnia which is supported by our results.

Association between symptoms of sleep apnea and problem behaviors in young adult twins and siblings.

BACKGROUND: Sleep apnea is one of the most common sleep disorders and it is related to multiple negative health consequences. Previous studies have shown that sleep apnea is influenced by genetic factors. However, studies have not investigated the genetic and environmental influences of symptoms of sleep apnea in young adults. Furthermore, the underpinnings of the relationship between apnea symptoms and internalizing/externalizing problems are unknown. The objectives of this study were to estimate the magnitude of: (1) genetic and environmental influences on self-reported apnea symptoms; (2) the relationship between self-reported apnea symptoms and internalizing/externalizing traits; (3) genetic and environmental influences on the associations between self-reported apnea symptoms, internalizing behaviors and externalizing behaviors. METHODS: In a twin/sibling study, univariate and multivariate models were fitted to estimate both individual variance and sources of covariance between symptoms of sleep apnea and internalizing/externalizing behaviors. RESULTS: Our results show that genetic influences account for 40% of the variance in sleep apnea symptoms. Moreover, there are modest associations between depression, anxiety and externalizing behaviors with apnea symptoms (ranging from r = 0.22-0.29). However, the origins of these associations differ. For example, whereas most of the covariation between symptoms of depression and sleep apnea can be explained by genes (95%), there was a larger role for the environment (53%) in the association between symptoms of anxiety and sleep apnea. CONCLUSIONS: Genetic factors explain a significant proportion of variance in symptoms of apnea and most of the covariance with depression.

Anticipated next-day demand affects the magnitude of the cortisol awakening response, but not subjective or objective sleep.

Whilst the association between sleep and stress is well established, few studies have examined the effects of an anticipated stressor upon sleep and relevant physiological markers. The aim of the present study was to examine whether an anticipated stressor in the form of next-day demand affects subjective and objective sleep, and multiple indices of the cortisol awakening response. Subjective and objective sleep and the cortisol awakening response were measured over three consecutive nights in 40 healthy adults in a sleep laboratory. During their second night, participants were informed that they would either be required to complete a series of demanding cognitive tasks, in a competition format, during the next day (anticipation condition; n = 22), or were given no instruction (sedentary condition; n = 18). Sleep was measured subjectively using sleep diaries, objectively using polysomnography, and saliva was measured at awakening, +15, +30, +45 and +60 min each morning, from which cortisol awakening response measurement indices were derived: awakening cortisol levels, the mean increase in cortisol levels and total cortisol secretion. There were no between-group differences in subjective or objective sleep in the night preceding the anticipated demand; however, compared with the sedentary condition, those in the anticipation group displayed a larger mean increase in cortisol levels, representing the cortisol awakening response magnitude, on the morning of the anticipated demand. Overall, the results suggest that whilst anticipated stress affected the subsequent cortisol awakening response, subjective and objective sleep remained undisturbed. It is possible that the timing of an anticipated stressor, rather than its expected duration, may influence subsequent sleep disruption.

Preferential attention towards the eye-region amongst individuals with insomnia.

People with insomnia often perceive their own facial appearance as more tired compared with the appearance of others. Evidence also highlights the eye-region in projecting tiredness cues to perceivers, and tiredness judgements often rely on preferential attention towards this region. Using a novel eye-tracking paradigm, this study examined: (i) whether individuals with insomnia display preferential attention towards the eye-region, relative to nose and mouth regions, whilst observing faces compared with normal-sleepers; and (ii) whether an attentional bias towards the eye-region amongst individuals with insomnia is self-specific or general in nature. Twenty individuals with DSM-5 Insomnia Disorder and 20 normal-sleepers viewed 48 neutral facial photographs (24 of themselves, 24 of other people) for periods of 4000 ms. Eye movements were recorded using eye-tracking, and first fixation onset, first fixation duration and total gaze duration were examined for three interest-regions (eyes, nose, mouth). Significant group × interest-region interactions indicated that, regardless of the face presented, participants with insomnia were quicker to attend to, and spent more time observing, the eye-region relative to the nose and mouth regions compared with normal-sleepers. However, no group × face × interest-region interactions were established. Thus, whilst individuals with insomnia displayed preferential attention towards the eye-region in general, this effect was not accentuated during self-perception. Insomnia appears to be characterized by a general, rather than self-specific, attentional bias towards the eye-region. These findings contribute to our understanding of face perception in insomnia, and provide tentative support for cognitive models of insomnia demonstrating that individuals with insomnia monitor faces in general, with a specific focus around the eye-region, for cues associated with tiredness.

Sustained wakefulness and visual attention: moderation by chronotype.

INTRODUCTION: Attentional networks are sensitive to sleep deprivation and increased time awake. However, existing evidence is inconsistent and may be accounted for by differences in chronotype or time-of-day. We examined the effects of sustained wakefulness over a normal "socially constrained" day (following 18 h of sustained wakefulness), following a night of normal sleep, on visual attention as a function of chronotype. METHODS: Twenty-six good sleepers (mean age 25.58; SD 4.26; 54 % male) completed the Attention Network Test (ANT) at two time points (baseline at 8 am; following 18-h sustained wakefulness at 2 am). The ANT provided mean reaction times (RTs), error rates, and the efficiency of three attentional networks-alerting, orienting, and executive control/conflict. The Morningness-Eveningness Questionnaire measured chronotype. RESULTS: Mean RTs were longer at time 2 compared to time 1 for those with increasing eveningness; the opposite was true for morningness. However, those with increasing morningness exhibited longer RT and made more errors, on incongruent trials at time 2 relative to those with increasing eveningness. There were no significant main effects of time or chronotype (or interactions) on attentional network scores. CONCLUSION: Sustained wakefulness produced differential effects on visual attention as a function of chronotype. Whilst overall our results point to an asynchrony effect, this effect was moderated by flanker type. Participants with increasing eveningness outperformed those with increasing morningness on incongruent trials at time 2. The preservation of executive control in evening-types following sustained wakefulness is likely driven by differences in circadian phase between chronotypes across the day.

Misperception of tiredness in young adults with insomnia.

People with insomnia often exhibit interpretive biases to cues associated with their condition. This study examined whether individuals with insomnia display an interpretive bias, such that they misperceive facial attributes of tiredness in a disorder-consistent manner. The efficacy of providing feedback related to the accuracy of participants' perception on later judgements of tiredness was further examined. Forty participants, 20 with DSM-5-defined insomnia disorder and 20 normal-sleepers, participated. The perception of one's own facial appearance of tiredness was assessed twice over two consecutive days using a visual task whereby participants indicated when a morphing image of their face represented their current level of tiredness. Visual and verbal feedback, related to participants' degree of misperception, was provided on completion of Day 1 testing. Overall, individuals with insomnia perceived their own face as significantly more tired than a baseline neutral photograph was, whereas normal-sleepers perceived themselves as appearing more alert. This pattern of results was only apparent on Day 1. Although no group × day interaction was established, mean scores suggest an improvement in perception on Day 2 amongst individuals with insomnia only. These findings suggest that individuals with insomnia exhibit a misperception of their facial attributes of tiredness, interpreting them in a disorder-consistent manner. This finding adds to the body of literature on cognitive models of insomnia, demonstrating more general cognitive biases in the disorder. Further, the results provide suggestive evidence that this misperception may be reformed.

Polymorphisms in the circadian expressed genes PER3 and ARNTL2 are associated with diurnal preference and GNß3 with sleep measures.

Sleep and circadian rhythms are intrinsically linked, with several sleep traits, including sleep timing and duration, influenced by both sleep homeostasis and the circadian phase. Genetic variation in several circadian genes has been associated with diurnal preference (preference in timing of sleep), although there has been limited research on whether they are associated with other sleep measurements. We investigated whether these genetic variations were associated with diurnal preference (Morningness-Eveningness Questionnaire) and various sleep measures, including: the global Pittsburgh Sleep Quality index score; sleep duration; and sleep latency and sleep quality. We genotyped 10 polymorphisms in genes with circadian expression in participants from the G1219 sample (n = 966), a British longitudinal population sample of young adults. We conducted linear regressions using dominant, additive and recessive models of inheritance to test for associations between these polymorphisms and the sleep measures. We found a significant association between diurnal preference and a polymorphism in period homologue 3 (PER3) (P < 0.005, recessive model) and a novel nominally significant association between diurnal preference and a polymorphism in aryl hydrocarbon receptor nuclear translocator-like 2 (ARNTL2) (P < 0.05, additive model). We found that a polymorphism in guanine nucleotide binding protein beta 3 (GNß3) was associated significantly with global sleep quality (P < 0.005, recessive model), and that a rare polymorphism in period homologue 2 (PER2) was associated significantly with both sleep duration and quality (P < 0.0005, recessive model). These findings suggest that genes with circadian expression may play a role in regulating both the circadian clock and sleep homeostasis, and highlight the importance of further studies aimed at dissecting the specific roles that circadian genes play in these two interrelated but unique behaviours.

Collateral effects of the COVID-19 pandemic on endocrine treatments for breast and prostate cancer in the UK: a cohort study.

Background: The COVID-19 pandemic affected cancer screening, diagnosis and treatments. Many surgeries were substituted with bridging therapies during the initial lockdown, yet consideration of treatment side effects and their management was not a priority. Objectives: To examine how the changing social restrictions imposed by the pandemic affected incidence and trends of endocrine treatment prescriptions in newly diagnosed (incident) breast and prostate cancer patients and, secondarily, endocrine treatment-related outcomes (including bisphosphonate prescriptions, osteopenia and osteoporosis), in UK clinical practice from March 2020 to June 2022. Design: Population-based cohort study using UK primary care Clinical Practice Research Datalink GOLD database. Methods: There were 13,701 newly diagnosed breast cancer patients and 12,221 prostate cancer patients with ⩾1-year data availability since diagnosis between January 2017 and June 2022. Incidence rates (IR) and incidence rate ratios (IRR) were calculated across multiple time periods before and after lockdown to examine the impact of changing social restrictions on endocrine treatments and treatment-related outcomes, including osteopenia, osteoporosis and bisphosphonate prescriptions. Results: In breast cancer patients, aromatase inhibitor (AI) prescriptions increased during lockdown versus pre-pandemic [IRR: 1.22 (95% confidence interval (CI): 1.11-1.34)], followed by a decrease post-first lockdown [IRR: 0.79 (95% CI: 0.69-0.89)]. In prostate cancer patients, first-generation antiandrogen prescriptions increased versus pre-pandemic [IRR: 1.23 (95% CI: 1.08-1.4)]. For breast cancer patients on AIs, diagnoses of osteopenia, osteoporosis and bisphosphonate prescriptions were reduced across all lockdown periods versus pre-pandemic (IRR range: 0.31-0.62). Conclusion: During the first 2 years of the pandemic, newly diagnosed breast and prostate cancer patients were prescribed more endocrine treatments compared to pre-pandemic due to restrictions on hospital procedures replacing surgeries with bridging therapies. But breast cancer patients had fewer diagnoses of osteopenia and osteoporosis and bisphosphonate prescriptions. These patients should be followed up in the coming years for signs of bone thinning. Evidence of poorer management of treatment-related side effects will help assess resource allocation for patients at high risk for bone-related complications.

Effects of the COVID-19 pandemic on hormone treatments for breast and prostate cancer in the UK: implications for bone health The COVID-19 pandemic has had a big impact on health, going beyond just causing illness. One area it has influenced is how patients with breast cancer or prostate cancer are treated. Surgeries and radiotherapies were delayed from the first lockdown as hospitals reduced non-covid related procedures. Some patients with breast or prostate cancer were instead given some medications to help stop their cancers from growing until they were able to have surgery or radiotherapy. These medications (called endocrine treatments) have important side effects, such as conditions that affect the bones. Patients on these medications should be monitored by doctors for signs of bone thinning and should, in some cases, be given other medications to help stop this happening. This study used doctors' records from more than 5 million people to find out whether the pandemic affected the number of endocrine medications being prescribed in patients with breast or prostate cancer, and also looked at the number of these patients that were diagnosed with conditions that affect their bones and whether they were given medications that could protect their bone health. We found that during the first lockdown, patients with breast cancer or prostate cancer had more of some types of endocrine treatments compared to before the lockdown. However, they had fewer diagnoses of conditions related to bone health and fewer medications to protect their bones. It is possible that appointments and tests that are usually carried out to diagnose conditions relating to bone health were not performed in the months after the first lockdown, and so these conditions were underdiagnosed. The use of medications to protect their bones was also reduced, likely because this was not considered a priority during the pandemic. This highlights that such patients should be followed up in the coming years for signs of bone thinning, given the relatively poorer management of these side effects in these people after the pandemic.

The impact of the UK COVID-19 lockdown on the screening, diagnostics and incidence of breast, colorectal, lung and prostate cancer in the UK: a population-based cohort study.

Introduction: The COVID-19 pandemic had collateral effects on many health systems. Cancer screening and diagnostic tests were postponed, resulting in delays in diagnosis and treatment. This study assessed the impact of the pandemic on screening, diagnostics and incidence of breast, colorectal, lung, and prostate cancer; and whether rates returned to pre-pandemic levels by December, 2021. Methods: This is a cohort study of electronic health records from the United Kingdom (UK) primary care Clinical Practice Research Datalink (CPRD) GOLD database. The study included individuals registered with CPRD GOLD between January, 2017 and December, 2021, with at least 365 days of clinical history. The study focused on screening, diagnostic tests, referrals and diagnoses of first-ever breast, colorectal, lung, and prostate cancer. Incidence rates (IR) were stratified by age, sex, and region, and incidence rate ratios (IRR) were calculated to compare rates during and after lockdown with rates before lockdown. Forecasted rates were estimated using negative binomial regression models. Results: Among 5,191,650 eligible participants, the first lockdown resulted in reduced screening and diagnostic tests for all cancers, which remained dramatically reduced across the whole observation period for almost all tests investigated. There were significant IRR reductions in breast (0.69 [95% CI: 0.63-0.74]), colorectal (0.74 [95% CI: 0.67-0.81]), and prostate (0.71 [95% CI: 0.66-0.78]) cancer diagnoses. IRR reductions for lung cancer were non-significant (0.92 [95% CI: 0.84-1.01]). Extrapolating to the entire UK population, an estimated 18,000 breast, 13,000 colorectal, 10,000 lung, and 21,000 prostate cancer diagnoses were missed from March, 2020 to December, 2021. Discussion: The UK COVID-19 lockdown had a substantial impact on cancer screening, diagnostic tests, referrals, and diagnoses. Incidence rates remained significantly lower than pre-pandemic levels for breast and prostate cancers and associated tests by December, 2021. Delays in diagnosis are likely to have adverse consequences on cancer stage, treatment initiation, mortality rates, and years of life lost. Urgent strategies are needed to identify undiagnosed cases and address the long-term implications of delayed diagnoses.

Modifiable lifestyle factors and the risk of post-COVID-19 multisystem sequelae, hospitalization, and death.

Effective prevention strategies for post-COVID complications are crucial for patients, clinicians, and policy makers to mitigate their cumulative burden. This study evaluated the association of modifiable lifestyle factors (smoking, alcohol intake, BMI, physical activity, sedentary time, sleep duration, and dietary habits) with COVID-19 multisystem sequelae, death, and hospitalization in the UK Biobank cohort (n = 68,896). A favorable lifestyle (6-10 healthy factors; 46.4%) was associated with a 36% lower risk of multisystem sequelae (HR, 0.64; 95% CI, 0.58-0.69; ARR at 210 days, 7.08%; 95% CI, 5.98-8.09) compared to an unfavorable lifestyle (0-4 factors; 12.3%). Risk reductions spanned all 10 organ systems, including cardiovascular, coagulation, metabolic, gastrointestinal, kidney, mental health, musculoskeletal, respiratory disorders, and fatigue. This beneficial effect was largely attributable to direct lifestyle impacts independent of corresponding pre-infection comorbidities (71% for any sequelae). A favorable lifestyle was also related to the risk of post-COVID death (HR 0.59, 0.52-0.66) and hospitalization (HR 0.78, 0.73-0.84). These associations persisted across acute and post-acute infection phases, irrespective of hospitalization status, vaccination, or SARS-CoV-2 variant. These findings underscore the clinical and public health importance of adhering to a healthy lifestyle in mitigating long-term COVID-19 adverse impacts and enhancing future pandemic preparedness.

The Impact of the COVID-19 Pandemic on Incidence and Short-Term Survival for Common Solid Tumours in the United Kingdom: A Cohort Analysis.

Purpose: The COVID-19 pandemic profoundly affected healthcare systems and patients. There is a need to comprehend the collateral effects of the pandemic on non-communicable diseases. We examined the impact of the pandemic on short-term survival for common solid tumours, including breast, colorectal, head and neck, liver, lung, oesophageal, pancreatic, prostate, and stomach cancer in the UK. Methods: This was a population-based cohort study of electronic health records from the UK primary care Clinical Practice Research Datalink GOLD database. In sum, 12,259,744 eligible patients aged ≥18 years with ≥1 year's history identified from January 2000 to December 2022 were included. We estimated age-standardised incidence and short-term (one- and two-year) survival for several common cancers from 2000 to 2019 (in five-year strata) and compared these to 2020-2022 using the Kaplan-Meier method. Results: Incidence decreased for most cancers in 2020 and recovered to different extents in 2021-2022. Short-term survival improved for most cancers between 2000 and 2019, but then declined, albeit minimally, for those diagnosed in 2020-2022. This was most pronounced for colorectal cancer, with one-year survival falling from 78.8% (95% CI 78%-79.6%) in 2015-2019 to 77% (95% CI 75.6-78.3%) for those diagnosed in 2020-2022. Conclusion: Short-term survival for many cancers was impacted, albeit minimally, by the pandemic in the UK, with reductions in survivorship from colorectal cancer equivalent to returning to the mortality seen in the first decade of the 2000s. While data on longer-term survival are needed to fully comprehend the impact of COVID-19 on cancer care, our findings illustrate the need for an urgent and substantial commitment from the UK National Health Service to address the existing backlog in cancer screening and diagnostic procedures to improve cancer care and mortality.

Sleep-related attentional bias in poor versus good sleepers is independent of affective valence.

Contradictory evidence exists relating to the presence of an attention bias to sleep-related stimuli in poor sleepers/insomnia using the emotional Stroop task (EST). These inconsistencies may be due to methodological issues related to the affective valence of the sleep-related stimuli. Thus, individuals may attend differentially to sleep-related stimuli not because of their 'sleep' properties, but their negativity. The current study addresses this by controlling the affective valence of sleep-related words. A total of 107 participants [mean age = 33.22 years, standard deviation (SD) = 12.31 years; 61.7% female] were recruited during an evening event at the Newcastle Science Festival. Participants completed the Pittsburgh Sleep Quality Index (PSQI) and a computerized EST containing 20 non-affective sleep-related, 20 neutral and 20 negatively valenced threat words. Good and poor sleepers were categorized using the PSQI. There were no significant differences between groups on response latency to sleep-related words (t(105) = -0.30, P = 0.76). However, the interaction between good versus poor sleepers and word-type on response latency was significant (F(2,210) = 3.06, P < 0.05). Poor sleepers took longer to respond to sleep-related words (mean = 723.35, SD = 172.55) compared to threat words (mean = 694.63, SD = 162.17) than good sleepers (mean = 713.20, SD = 166.32; and mean = 716.65, SD = 181.14). The results demonstrate the presence of an attention bias towards sleep-related stimuli compared to threat stimuli in poor sleepers. Accordingly, poor sleepers may be consumed by stimuli relevant to their specific difficulties, as well as being more highly attuned to negative cues that signal anxious states. Thus, the present research suggests that there are two opposing forces at play: one which facilitates performance (non-specific threats) and one which hinders performance (personally relevant threats).

The Genesis 12-19 (G1219) Study: a twin and sibling study of gene-environment interplay and adolescent development in the UK.

The Genesis 12-19 (G1219) Study is an ongoing longitudinal study of a sample of UK twin pairs, non-twin sibling pairs, and their parents. G1219 was initially designed to examine the role of gene-environment interplay in adolescent depression. However, since then data have continued to be collected from both parents and their offspring into young adulthood. This has allowed for longitudinal analyses of depression and has enabled researchers to investigate multiple phenotypes and to ask questions about intermediate mechanisms. The study has primarily focused on emotional development, particularly depression and anxiety, which have been assessed at multiple levels of analysis (symptoms, cognitions, and relevant environmental experiences). G1219 has also included assessment of a broader range of psychological phenotypes ranging from antisocial behaviors and substance use to sleep difficulties, in addition to multiple aspects of the environment. DNA has also been collected. The first wave of data collection began in the year 1999 and the fifth wave of data collection will be complete before the end of 2012. In this article, we describe the sample, data collection, and measures used. We also summarize some of the key findings to date.

Replication of Genome-Wide Association Studies (GWAS) loci for sleep in the British G1219 cohort.

Sleep is a critical behavior shared by most higher animals. Sleep disturbances are comorbid with numerous psychiatric disorders, most notably symptoms of depression. Twin studies have suggested that genetic influences partially underlie the variation seen for numerous sleep-related traits across individuals. Recently, two Genome-Wide Association Studies (GWAS) conducted for sleep traits have revealed new candidate genes for sleep-related measures. We attempted to replicate the two most significant associations from these two studies, CACNA1C (a l-type calcium channel) with sleep latency and quality and ABCC9 (an ATP-sensitive potassium channel) with sleep duration, using the G1219 British population sample. We genotyped single-nucleotide polymorphisms (SNPs) for each of the two different sleep GWAS loci. Linear regression analyses were conducted to assess main effects of these SNPs on their corresponding sleep measures, as well as for depressive symptoms. We successfully replicated an association of a genetic variant in the CACNA1C gene (rs16929277) with sleep quality using an additive model of inheritance. A significant association of the ABCC9 gene (rs11046209) with sleep duration was seen only in a recessive models based upon a rare homozygous genotype (n = 2). There was also a significant association between a different ABCC9 gene variant (rs11046205) and depressive symptoms. These findings add further support for the involvement of calcium channels in the mechanisms regulating sleep function and suggest a possible role of the ABCC9 gene in depression.

Problematic technology use and sleep quality in young adulthood: novel insights from a nationally representative twin study.

STUDY OBJECTIVES: Digital technology use is associated with poor sleep quality in adolescence and young adulthood although research findings have been mixed. No studies have addressed the association between the two using a genetically informative twin design which could extend our understanding of the etiology of this relationship. This study aimed to test: (1) the association between adolescents' perceived problematic use of digital technology and poor sleep quality, (2) whether the association between problematic use of technology and poor sleep quality remains after controlling for familial factors, and (3) genetic and environmental influences on the association between problematic use of technology and poor sleep quality. METHODS: Participants were 2232 study members (18-year-old twins) of the Environmental Risk (E-Risk) Longitudinal Twin Study. The sample was 48.9% male, 90% white, and 55.6% monozygotic. We conducted regression and twin difference analyses and fitted twin models. RESULTS: Twin differences for problematic use of technology were associated with differences for poor sleep quality in the whole sample (p < 0.001; B = 0.15) and also when we limited the analyses to identical twins only (p < 0.001; B = 0.21). We observed a substantial genetic correlation between problematic use of technology and sleep quality (rA = 0.31), whereas the environmental correlation was lower (rE = 0.16). CONCLUSIONS: Adolescent reported problematic use of digital technology is associated with poor sleep quality-even after controlling for familial factors including genetic confounds. Our results suggest that the association between adolescents' sleep and problematic digital technology use is not accounted for by shared genetic liability or familial factors but could reflect a causal association. This robust association needs to be examined in future research designed to test causal associations.

Nonshared environmental influences on sleep quality: a study of monozygotic twin differences.

Research has consistently demonstrated that environmental influences are important for explaining the variability in sleep quality observed in the general population. Although there is substantial evidence assessing associations between sleep quality and a host of environmental variables, it is possible that their effects are mediated by genetic influence. A monozygotic twin differences design was used to assess the specific contribution of nonshared environmental influences on sleep quality, whilst controlling for genetic and shared environmental effects in a sample of 380 monozygotic twins (mean age 19.8 years, SD = 1.26, range = 18-22 years). Participants completed the Pittsburgh Sleep Quality Index and questionnaires assessing several candidate "environmental" measures. When controlling for genetic and shared environmental effects, within monozygotic twin-pair differences in sleep quality were associated with within monozygotic twin-pair differences in general health for males (ß = 1.56, p < 0.001) and relationship satisfaction for females (ß = 1.01, p < 0.05). For the remaining environmental measures the results suggest that these seemingly "environmental" influences are actually in part dependent on genetics and/or the shared environment. These findings give insight into how specific environments affect sleep and the possible mechanisms behind these associations.

Anxiety sensitivity in adolescence and young adulthood: the role of stressful life events, 5HTTLPR and their interaction.

BACKGROUND: Cognitive biases have long been hypothesized to influence the development and maintenance of symptoms of internalizing problems. Anxiety sensitivity represents one such bias and refers to sensitivity to the physical and emotional symptoms of anxiety and the belief that these are harmful. Twin studies indicate a role for both environmental and genetic influences on anxiety sensitivity. However, little work has been done specifying environments or genes involved in this phenotype. In light of this, we looked at the association between stressful life events, the serotonin transporter gene polymorphism (5HTTLPR), and anxiety sensitivity in a longitudinal sample of adolescents. METHODS: Stressful life events and anxiety sensitivity were measured in over 1,500 individuals at three time points (mean ages 15, 17, and 20 years). 5HTTLPR was genotyped in 1,109 participants. RESULTS: There was consistent evidence for an association between stressful life events and both anxiety sensitivity and change in anxiety sensitivity over time. Although the effect of independent stressful life events was relatively short lived, dependent stressful life events were associated with anxiety sensitivity over time. There was no evidence for a main effect of 5HTTLPR on anxiety sensitivity. 5HTTLPR genotype did not moderate the effect of stressful life events on anxiety sensitivity. CONCLUSIONS: The current study extends previous work by showing that stressful life events, independent of the individual, explained change in cognitions associated with anxiety and depression. This effect does not, however, appear to be moderated by genotype.

Pre-Sleep Cognitive Arousal Is Unrelated to Sleep Misperception in Healthy Sleepers When Unexpected Sounds Are Played during Non-Rapid Eye Movement Sleep: A Polysomnography Study.

BACKGROUND: It is well-established that environmental noise can disrupt sleep, and cause a mismatch between subjective and objective sleep, which is known as "sleep misperception". Naturalistic studies indicate that pre-sleep cognitive arousal and sleep misperception are associated in the context of noise. However, it is not known if this is the case when ecologically valid noises are specifically played during non-rapid eye movement (NREM) sleep, which is susceptible to noise-related disruption. The present study evaluated if pre-sleep cognitive arousal was associated with sleep misperception in healthy normal sleepers, when unexpected ecologically valid common nocturnal noises were played during NREM sleep. METHODS: Eighteen healthy sleepers (Mage = 23.37 years, SDage = 3.21 years) participated. Sleep was measured objectively on three consecutive nights using polysomnography, in a sleep laboratory environment, and subjectively, through participant estimates of total sleep time (TST). Night 1 was a baseline night where no noises were played. On Night 2, noises, which were chosen to be representative of habitual nocturnal noises heard in home environments, were played to participants via in-ear headphones after 5 min of objective sleep. RESULTS: Unexpectedly, habitual pre-sleep cognitive arousal was not associated with subjective-objective TST discrepancy on Night 2. CONCLUSIONS: These results suggest that in healthy sleepers, when ecologically valid noises are played unexpectedly during NREM sleep in an unfamiliar sleep laboratory environment the subjective experience of sleep is not associated with pre-sleep cognitive arousal, or negatively impacted by noise exposure.

Pre-Sleep Cognitive Arousal Is Negatively Associated with Sleep Misperception in Healthy Sleepers during Habitual Environmental Noise Exposure: An Actigraphy Study.

Specific noises (e.g., traffic or wind turbines) can disrupt sleep and potentially cause a mismatch between subjective sleep and objective sleep (i.e., "sleep misperception"). Some individuals are likely to be more vulnerable than others to noise-related sleep disturbances, potentially as a result of increased pre-sleep cognitive arousal. The aim of the present study was to examine the relationships between pre-sleep cognitive arousal and sleep misperception. Sixteen healthy sleepers participated in this naturalistic, observational study. Three nights of sleep were measured using actigraphy, and each 15-s epoch was classified as sleep or wake. Bedside noise was recorded, and each 15-s segment was classified as containing noise or no noise and matched to actigraphy. Participants completed measures of habitual pre-sleep cognitive and somatic arousal and noise sensitivity. Pre-sleep cognitive and somatic arousal levels were negatively associated with subjective−objective total sleep time discrepancy (p < 0.01). There was an association between sleep/wake and noise presence/absence in the first and last 90 min of sleep (p < 0.001). These results indicate that higher levels of habitual pre-sleep arousal are associated with a greater degree of sleep misperception, and even in healthy sleepers, objective sleep is vulnerable to habitual bedside noise.

Sleep quality and diurnal preference in a sample of young adults: associations with 5HTTLPR, PER3, and CLOCK 3111.

Research investigating associations between specific genes and individual differences with regards to the quality and timing of sleep has primarily focussed on serotonin-related and clock genes. However, there are only a few studies of this type and most of those to date have not considered the possibility of gene-environment interaction. Here, we describe associations between sleep quality and diurnal preference and three functional polymorphisms: 5HTTLPR, PERIOD3, and CLOCK 3111. Furthermore, we assessed whether associations between genotypes and sleep phenotypes were moderated by negative life events-a test of gene-environment interaction. DNA from buccal swabs was collected from 947 individuals [mean age = 20.3 years (SD = 1.77), age range = 18-27 years; 61.8% female] and genotyped for the three polymorphisms. Participants completed the Pittsburgh Sleep Quality Index and the Morningness-Eveningness Questionnaire. There was a significant main effect of 5HTTLPR on sleep quality, indicating that "long-long" homozygotes experienced significantly poorer sleep quality (mean = 6.35, SD = 3.36) than carriers of at least one "short" allele (mean = 5.67, SD = 2.96; ß = -0.34, P = 0.005). There were no main effects of 5HTTLPR on diurnal preference; no main effects of PERIOD3 or CLOCK on sleep quality or diurnal preference; and no significant interactions with negative life events. The main effect of the "long" 5HTTLPR allele contradicts previous research, suggesting that perhaps the effects of this gene are heterogeneous in different populations. Failure to replicate previous research in relation to PERIOD3 and CLOCK concurs with previous research suggesting that the effects of these genes are small and may be related to population composition.