Enhanced influenza A H1N1 T cell epitope recognition and cross-reactivity to protein-O-mannosyltransferase 1 in Pandemrix-associated narcolepsy type 1.

Narcolepsy type 1 (NT1) is a chronic neurological disorder having a strong association with HLA-DQB1*0602, thereby suggesting an immunological origin. Increased risk of NT1 has been reported among children or adolescents vaccinated with AS03 adjuvant-supplemented pandemic H1N1 influenza A vaccine, Pandemrix. Here we show that pediatric Pandemrix-associated NT1 patients have enhanced T-cell immunity against the viral epitopes, neuraminidase 175-189 (NA175-189) and nucleoprotein 214-228 (NP214-228), but also respond to a NA175-189-mimic, brain self-epitope, protein-O-mannosyltransferase 1 (POMT1675-689). A pathogenic role of influenza virus-specific T-cells and T-cell cross-reactivity in NT1 are supported by the up-regulation of IFN-γ, perforin 1 and granzyme B, and by the converging selection of T-cell receptor TRAV10/TRAJ17 and TRAV10/TRAJ24 clonotypes, in response to stimulation either with peptide NA175-189 or POMT1675-689. Moreover, anti-POMT1 serum autoantibodies are increased in Pandemrix-vaccinated children or adolescents. These results thus identify POMT1 as a potential autoantigen recognized by T- and B-cells in NT1.

Narcolepsy patients' blood-based miRNA expression profiling: miRNA expression differences with Pandemrix vaccination.

OBJECTIVES: Narcolepsy is a neurological sleep disorder characterized by excessive daytime sleepiness and nighttime sleep disturbance. Among children and adolescents vaccinated with Pandemrix vaccine in Finland and Sweden, the number of narcolepsy cases increased. Our aim was to identify miRNAs involved in narcolepsy and their association with Pandemrix vaccination. MATERIALS AND METHODS: We performed global miRNA proofing by miRNA microarrays followed by RT-PCR verification on 20 narcolepsy patients (Pandemrix-associated and Pandemrix-non-associated) and 17 controls (vaccinated and non-vaccinated). RESULTS: Between all narcolepsy patients and controls, 11 miRNAs were differentially expressed; 17 miRNAs showed significantly differential expression between Pandemrix-non-associated narcolepsy patients and non-vaccinated healthy controls. MiR-188-5p and miR-4499 were over-expressed in narcolepsy patients vs healthy controls. Two miRNAs, miR-1470 and miR-4455, were under-expressed in Pandemrix-associated narcolepsy patients vs Pandemrix-non-associated narcolepsy patients. CONCLUSIONS: We identified miRNA expression patterns in narcolepsy patients that linked them to mRNA targets known to be involved in brain-related pathways or brain disorders.

Sleeping difficulties and health-related quality of life in Parkinson's disease.

OBJECTIVE: Various sleep-related symptoms occur in Parkinson's disease (PD). Their occurrence with health-related quality of life (HRQL), comorbid sleep disorders, and other comorbidities was studied. METHODS: Altogether, 1447 randomly selected patients with Parkinson's disease, aged 43-89 years, participated in a questionnaire study. A structured questionnaire with 207 items was based on the Basic Nordic Sleep Questionnaire. Questions on demographics, PD, sleep disorders, and comorbidities were included. RESULTS: The response rate was 59.0%, and of these, 80% had answered to all questions that were used in the analyses (N=684). Occurrence of long sleep was found in 26.2% of the subjects, short sleep in 32.5%, poor sleep in 21.2%, sleep deprivation in 33.8%, disrupted sleep in 47.4%, and difficulties to fall asleep in 12.2%, respectively. Poor self-rated health and poor quality of life occurred in 44.4% and in 43.3% of all participants. In the logistic regression, age and gender differentially predicted long sleep and sleep deprivation, such that older age and being male were positively associated with long sleep but negatively associated with the report of sleep deprivation. Depression, subjective negative stress, and fatigue occurred with long sleep. On the other hand, poor sleep and excessive daytime sleepiness occurred with short sleep and sleep deprivation. CONCLUSIONS: The sleep difficulties in PD are frequent. The long sleeping patients have depression, stress, and fatigue.

A coordinated cross-disciplinary research initiative to address an increased incidence of narcolepsy following the 2009-2010 Pandemrix vaccination programme in Sweden.

In response to the 2009-2010 influenza A(H1N1)pdm09 pandemic, a mass vaccination programme with the AS03-adjuvanted influenza A(H1N1) vaccine Pandemrix was initiated in Sweden. Unexpectedly, there were a number of narcolepsy cases amongst vaccinated children and adolescents reported. In this review, we summarize the results of a joint cross-disciplinary national research effort to investigate the adverse reaction signal from the spontaneous reporting system and to better understand possible causative mechanisms. A three- to fourfold increased risk of narcolepsy in vaccinated children and adolescents was verified by epidemiological studies. Of importance, no risk increase was observed for the other neurological and autoimmune diseases studied. Genetic studies confirmed the association with the allele HLA-DQB1*06:02, which is known to be related to sporadic narcolepsy. Furthermore, a number of studies using cellular and molecular experimental models investigated possible links between influenza vaccination and narcolepsy. Serum analysis, using a peptide microarray platform, showed that individuals who received Pandemrix exhibited a different epitope reactivity pattern to neuraminidase and haemagglutinin, as compared to individuals who were infected with H1N1. Patients with narcolepsy were also found to have increased levels of interferon-gamma production in response to streptococcus-associated antigens. The chain of patient-related events and the study results emerging over time were subjected to intense nationwide media attention. The importance of transparent communication and collaboration with patient representatives to maintain public trust in vaccination programmes is also discussed in the review. Organizational challenges due to this unexpected event delayed the initiation of some of the research projects, still the main objectives of this joint, cross-disciplinary research effort were reached, and important insights were acquired for future, similar situations in which a fast and effective task force may be required to evaluate vaccination-related adverse events.

Rapid eye movement sleep behavior disorder: devising controlled active treatment studies for symptomatic and neuroprotective therapy--a consensus statement from the International Rapid Eye Movement Sleep Behavior Disorder Study Group.

OBJECTIVES: We aimed to provide a consensus statement by the International Rapid Eye Movement Sleep Behavior Disorder Study Group (IRBD-SG) on devising controlled active treatment studies in rapid eye movement sleep behavior disorder (RBD) and devising studies of neuroprotection against Parkinson disease (PD) and related neurodegeneration in RBD. METHODS: The consensus statement was generated during the fourth IRBD-SG symposium in Marburg, Germany in 2011. The IRBD-SG identified essential methodologic components for a randomized trial in RBD, including potential screening and diagnostic criteria, inclusion and exclusion criteria, primary and secondary outcomes for symptomatic therapy trials (particularly for melatonin and clonazepam), and potential primary and secondary outcomes for eventual trials with disease-modifying and neuroprotective agents. The latter trials are considered urgent, given the high conversion rate from idiopathic RBD (iRBD) to Parkinsonian disorders (i.e., PD, dementia with Lewy bodies [DLB], multiple system atrophy [MSA]). RESULTS: Six inclusion criteria were identified for symptomatic therapy and neuroprotective trials: (1) diagnosis of RBD needs to satisfy the International Classification of Sleep Disorders, second edition, (ICSD-2) criteria; (2) minimum frequency of RBD episodes should preferably be ⩾2 times weekly to allow for assessment of change; (3) if the PD-RBD target population is included, it should be in the early stages of PD defined as Hoehn and Yahr stages 1-3 in Off (untreated); (4) iRBD patients with soft neurologic dysfunction and with operational criteria established by the consensus of study investigators; (5) patients with mild cognitive impairment (MCI); and (6) optimally treated comorbid OSA. Twenty-four exclusion criteria were identified. The primary outcome measure for RBD treatment trials was determined to be the Clinical Global Impression (CGI) efficacy index, consisting of a four-point scale with a four-point side-effect scale. Assessment of video-polysomnographic (vPSG) changes holds promise but is costly and needs further elaboration. Secondary outcome measures include sleep diaries; sleepiness scales; PD sleep scale 2 (PDSS-2); serial motor examinations; cognitive indices; mood and anxiety indices; assessment of frequency of falls, gait impairment, and apathy; fatigue severity scale; and actigraphy and customized bed alarm systems. Consensus also was established for evaluating the clinical and vPSG aspects of RBD. End points for neuroprotective trials in RBD, taking lessons from research in PD, should be focused on the ultimate goal of determining the performance of disease-modifying agents. To date no compound with convincing evidence of disease-modifying or neuroprotective efficacy has been identified in PD. Nevertheless, iRBD patients are considered ideal candidates for neuroprotective studies. CONCLUSIONS: The IRBD-SG provides an important platform for developing multinational collaborative studies on RBD such as on environmental risk factors for iRBD, as recently reported in a peer-reviewed journal article, and on controlled active treatment studies for symptomatic and neuroprotective therapy that emerged during the 2011 consensus conference in Marburg, Germany, as described in our report.

Orexin receptor antagonism, a new sleep-enabling paradigm: a proof-of-concept clinical trial.

The orexin system is a key regulator of sleep and wakefulness. In a multicenter, double-blind, randomized, placebo-controlled, two-way crossover study, 161 primary insomnia patients received either the dual orexin receptor antagonist almorexant, at 400, 200, 100, or 50 mg in consecutive stages, or placebo on treatment nights at 1-week intervals. The primary end point was sleep efficiency (SE) measured by polysomnography; secondary end points were objective latency to persistent sleep (LPS), wake after sleep onset (WASO), safety, and tolerability. Dose-dependent almorexant effects were observed on SE , LPS , and WASO . SE improved significantly after almorexant 400 mg vs. placebo (mean treatment effect 14.4%; P < 0.001). LPS (­18 min (P = 0.02)) and WASO (­54 min (P < 0.001)) decreased significantly at 400 mg vs. placebo. Adverse-event incidence was dose-related. Almorexant consistently and dose-dependently improved sleep variables. The orexin system may offer a new treatment approach for primary insomnia.

Effect of weight loss on inflammation in patients with mild obstructive sleep apnea.

BACKGROUND AND AIMS: Inflammation may be one mediating mechanism for cardiovascular diseases in obstructive sleep apnea (OSA). However, little is known about subclinical inflammation or the effect of lifestyle intervention on inflammation in early stages of OSA. The aim of this substudy of an existing randomized controlled trial, with post hoc analyses, was to determine the impact of lifestyle changes aimed at weight reduction on inflammatory biomarkers in overweight patients with mild OSA. METHODS AND RESULTS: Patients were randomized to supervised intensive lifestyle intervention group (N=28) or to control group (N=31), which received routine lifestyle advices. Circulating concentrations of pro- and anti-inflammatory mediators were measured before and after the 1-year intervention. The concentrations of two pro-inflammatory mediators, high-sensitivity C-reactive protein (hsCRP) and interleukin (IL)-6, decreased significantly in both groups. Although the changes in inflammatory biomarkers favored the supervised lifestyle intervention, the only significant reduction observed between the groups was for the anti-inflammatory IL-1 receptor antagonist (IL-1RA). The change in hsCRP was associated with apnea-hypopnea index, and improving night-time oxygen saturation was related to tumor necrosis factor alpha. IL-1RA and IL-6 were associated with insulin metabolism. CONCLUSION: Weight loss resulted in reductions in concentrations of some pro- and anti-inflammatory mediators in overweight patients with mild OSA, overall favoring the supervised lifestyle intervention. These findings suggest that more intensive treatment of obesity in OSA patients might be well-justified.

Increase in non-transferrin bound iron and the oxidative stress status in epilepsy patients treated using valproic acid monotherapy.

OBJECTIVE: This study aims to investigate the alteration of iron homeostasis and oxidative stress status in epilepsy patients treated with valproic acid (VPA) monotherapy. MATERIALS: 24 epilepsy patients receiving VPA monotherapy (12 men, 12 women, age 27.5 ± 7.2 y) and 24 sex- and age-matched healthy volunteers were included in the study. METHODS: The level of iron status parameters; serum iron, ferritin, transferrin saturation, non-transferrin bound iron (NTBI), serum level of trace elements (copper, zinc and selenium), concentration of antioxidant parameters, activities of antioxidant enzymes and level of lipid peroxidation product were determined. RESULTS: NTBI was found in the patients although their other iron status parameters were normal. Levels of antioxidant parameters were decreased while activities of antioxidant enzymes were increased. Levels of serum MDA were significantly increased in patients with epilepsy. The daily dose of valproic acid associated was statistically significant: serum concentration of NTBI (r = 0.579; p = 0.003) and MDA (r = 0.465; p = 0.022). A positive correlation existed between NTBI and zinc (r = 0.522; p = 0.009). CONCLUSION: According to our results, VPA treatment in patients with epilepsy contributes to the metabolism of iron, leading to the formation of NTBI and an increase in oxidative stress.

Evening types are more often current smokers and nicotine-dependent-a study of Finnish adult twins.

AIMS: To examine the association between diurnal type and smoking status and nicotine dependence (ND). DESIGN: A cohort study using random-effects model regressions for repeated longitudinal panel data was used to analyse smoking status by diurnal type. Regression analyses examined the association between diurnal type and ND. PARTICIPANTS: A total of 23, 289 same-sex adult twin individuals from Finnish Twin Cohort. Nicotine dependence was studied in a subsample of 676 twin individuals. MEASUREMENTS: Subjects were classified by self-report into four categories: morning type, somewhat morning type, somewhat evening type, evening type (in 1981). Smoking status was defined as current and ever smoking (in 1975, 1981 and 1990). ND was measured by DSM-IV and Fagerström Test for Nicotine Dependence (FTND) (during 2001-05). Findings Evening types of both genders were much more likely to be current (OR = 2.91, 95% CI 2.50, 3.38) and life-time smokers (OR = 2.67, 95% CI 2.96, 4.07) compared to morning types. Evening types were less likely to stop smoking. The risk of nicotine dependence assessed by DSM-IV criteria was higher among evening types (OR = 2.78, 95% CI 1.64, 4.72). Evening types scored 0.59 (95% CI 0.01, 1.17) points higher than morning types on the FTND. Adjustment for potential confounders did not change these associations. CONCLUSIONS: Being an evening type is associated independently with a higher risk of being a current smoker, being more highly dependent upon cigarettes and a lower likelihood of stopping smoking. Understanding the cause of these associations could elucidate the causes of tobacco addiction.

AASM standards of practice compliant validation of actigraphic sleep analysis from SOMNOwatch™ versus polysomnographic sleep diagnostics shows high conformity also among subjects with sleep disordered breathing.

In recent AASM practice, parameter actimetry is cited to measure total sleep time in obstructive sleep apnoea patients, when polysomnography is not available. An actigraph was therefore compared to polysomnographic data in 28 subjects with known sleep disordered breathing. Total sleep time (TST), sleep period time (SPT), sleep efficiency (SE), sustained sleep efficiency (SSE), sleep onset latency (SL) and sleep/wake pattern were compared to gold standard polysomnography. The results of an epoch-by-epoch comparison of sleep/wake from actigraphy to sleep stages from polysomnography gave a sensitivity of 90.2%, a specificity of 95.2% and an overall accuracy of 85.9%. Correlations were moderately strong for SE (0.71, p < 0.001) and SSE (0.65, p < 0.001) and high for TST (0.89, p < 0.001), SPT (0.91, p < 0.001) and SL (0.89, p < 0.001). It was concluded that actigraphy is not identical with PSG recording but gives good results in sleep/wake patterns and predicting TST, SPT, SSE, SE and SL also in sleep apnoea patients not suffering from other sleep disorders. The difficult detection of correct sleep onset causes SSE and SL to be less predictable. Therefore a 15-epoch criterion was introduced and resulted in high correlation of 0.89 for sleep latency, but has to be tested on a bigger population.

Bruxism and sleep efficiency measured at home with wireless devices.

The present study comprised 101 (48 men) employees of the Finnish Broadcasting Company with or without irregular shift work, but all with a work week of five shifts in a row followed by 2 days off. The mean age of the subjects was 41.0 years (SD = 9.9). The BiteStrip, a single-use disposable EMG device was used for one night during the work week to detect sleep bruxism. The Actiwatch Plus actigraph was worn on the non-dominant wrist for the entire week to evaluate sleep. Total sleep time and fragmentation index, the latter as a measure of sleep efficiency was calculated for the present study. The BiteStrip scores among the participants were: 0- no bruxism: 52.2% (according to the manufacturer, comparable to a sleep laboratory bruxism count of up to 39 over 5 h), 1- mild: 29.3% (40-74 counts), 2- moderate: 12.0%: (75-124 counts) and 3- severe: 6.5% (>125 counts). Severe bruxers slept less during the work week than non-bruxers (P = 0.009), but severe bruxers slept slightly more than non-bruxers during days off. The group means of the sleep fragmentation index decreased from start towards the middle of the work week and increased during days off (P = 0.016). The levels of the fragmentation indices were consistently higher in accordance with bruxism severity (P = 0.013). It was concluded that bruxism has a coherent relationship with sleep efficiency and it can be detected at home with a low cost device.

Developing ICF Core Sets for persons with sleep disorders based on the International Classification of Functioning, Disability and Health.

BACKGROUND: With the International Classification of Functioning, Disability and Health (ICF), we can now rely on a globally agreed-upon framework and system for classifying the typical spectrum of problems in the functioning of persons given the environmental context in which they live. ICF Core Sets are subgroups of ICF items selected to capture those aspects of functioning that are most likely to be affected by sleep disorders. OBJECTIVE: The objective of this paper is to outline the developmental process for the ICF Core Sets for Sleep. METHODS: The ICF Core Sets for Sleep will be defined at an ICF Core Sets Consensus Conference, which will integrate evidence from preliminary studies, namely (a) a systematic literature review regarding the outcomes used in clinical trials and observational studies, (b) focus groups with people in different regions of the world who have sleep disorders, (c) an expert survey with the involvement of international clinical experts, and (d) a cross-sectional study of people with sleep disorders in different regions of the world. CONCLUSION: The ICF Core Sets for Sleep are being designed with the goal of providing useful standards for research, clinical practice and teaching. It is hypothesized that the ICF Core Sets for Sleep will stimulate research that leads to an improved understanding of functioning, disability, and health in sleep medicine. It is of further hope that such research will lead to interventions and accommodations that improve the restoration and maintenance of functioning and minimize disability among people with sleep disorders throughout the world.

Sleep-disordered breathing is related to an increased risk for type 2 diabetes in middle-aged men, but not in women--the FIN-D2D survey.

AIM: To determine the association between sleep-disordered breathing (SDB) and obesity, diabetes and glucose intolerance among middle-aged men and women in Finland. METHODS: A multicentre, population-based, cross-sectional survey in Finland. A total of 1396 men and 1500 women aged 45-74 years participated in the survey between 2004 and 2005. The study subjects underwent a health examination including an oral glucose tolerance test and filled a questionnaire describing their sleep habits. RESULTS: Middle-aged men with SDB had an increased prevalence of diabetes and abnormal glucose tolerance. These associations were not found among middle-aged women. After adjustments for age, body mass index, smoking and central nervous system-affecting medication, SDB was independently associated with diabetes and glucose intolerance in men, but not in women. CONCLUSION: Middle-aged men with SDB have an independent risk of type 2 diabetes. However, both diabetes and SDB exhibit a strong association with obesity and especially with central obesity, reflecting increased visceral fat. In clinical practice especially male patients with diabetes should always be asked about habitual snoring and about possible sleep apnoea.

Sleep-related disturbances and physical inactivity are independently associated with obesity in adults.

OBJECTIVE: To study relationships between obesity, physical inactivity and sleep-related disturbances (obstructive sleep apnea (OSA), sleep duration, sleep disturbances concomitant with daytime tiredness) in adults (> or =30 years). DESIGN: Cross-sectional study with a random population sample. PARTICIPANTS: A total of 3377 men (mean age 52.3, s.d. 14.8, years) and 4264 women (56.4, s.d. 17.2, years). MAIN OUTCOME MEASURES: Dependent variables, measured: Waist circumference (WC) and body mass index (BMI). Independent variables, from a detailed interview/questionnaire: probable OSA, other sleep-related disturbances, sleep duration, type and frequency of leisure physical activity. Age, mental health, smoking and education were included in analyses as potential confounders. RESULTS: In men, OSA and physical inactivity increased likelihood for abdominal obesity (WC > or =102 cm). Physical inactivity also increased, but long (> or =9 h/day) sleep decreased likelihood for abdominal overweight (WC: 94-101 cm) in men. In women, abdominal obesity (WC > or =88 cm) was associated positively with OSA, moderate sleep-related disturbances, and physical inactivity. Education modulated the influence of age on abdominal obesity in both genders. Using BMI as the dependent variable did not change the general information obtained by the model. In addition, abdominal obesity was found to be an independent risk factor also in multivariable models predicting categories of a combined sleep duration and sleep disturbances. CONCLUSIONS: Sleep duration and sleep-related disturbances are associated with obesity, even after controlling for OSA and physical inactivity. The results support the hypothesis of vicious circle between sleep and obesity.

Unchanged striatal dopamine transporter availability in narcolepsy: a PET study with [11C]-CFT.

OBJECTIVE: To investigate dopamine reuptake sites (dopamine transporter) in the caudate nucleus and putamen in narcolepsy. PATIENTS AND METHODS: Ten patients with narcolepsy and 15 controls were studied with positron emission tomography. A cocaine analogue [11C]-CFT was used as a radioligand. RESULTS: The uptake of[11C]-CFT was within normal limits (89% of age-adjusted control mean in the caudate nucleus and 91% in the putamen) in patients with narcolepsy. CONCLUSIONS: No evidence of altered striataldopamine transporter availability was found in narcolepsy.

Effects of after-midnight intake of zolpidem and temazepam on driving ability in women with non-organic insomnia.

BACKGROUND: Occasionally, insomniac patients may take a sleeping pill after midnight. This may have consequences on their ability to drive a car and result in an increased risk of car accidents. METHODS: This double-blind, randomized, placebo-controlled, three-treatment three-period cross-over study investigated the effects of two frequently prescribed hypnotics of different classes in a real life condition on driving performance and psychomotor skills in insomniac women. Single doses of zolpidem 10 mg (Z), temazepam 20 mg (T) or placebo (P) were administered at 2:00 a.m. to 19 women aged 35-60 years in three treatment periods separated by wash-out periods of 3-14 days. After polysomnography at baseline and each treatment night, patients underwent, 5.5 h after drug intake at 7:30 a.m. on the next morning, a STISIM driving simulator test, and a subsequent neuropsychological test (FePsy). RESULTS: Eighteen insomniac women were included in the analysis (mean age 50 years, mean weight 69 kg, mean BMI 25.6 kg/m2). There were no differences between treatments for the primary outcome measure (mean time to collision; baseline: 0.120 s, P: 0.124, T: 0.118, Z: 0.124; P> or =0.12 for all pairwise comparisons). No differences were recorded for speed deviation and reaction time to tasks for the verum treatments, however, lane position deviation was greater after administration of zolpidem in comparison to both placebo and temazepam (P=0.025 and 0.05, respectively). There were no differences between treatments in the FePsy test. Both medications were well tolerated. CONCLUSIONS: 5.5 h after drug administration there were no major differences in psychomotor performances between both zolpidem and temazepam compared to placebo, which indicates the absence of significant residual effects at that time. However, certain patients were more susceptible than others to the drug effects (two patients with high number of collisions). This underlines the necessity to strongly advocate against the late intake of hypnotics if patients intend to drive a car early the next morning.

Sleep and its disturbance in a variant form of late infantile neuronal ceroid lipofuscinosis (CLN5).

To examine the nature of sleep disturbance in patients with a variant form of late infantile neuronal ceroid lipofuscinosis (CLN5), we studied 12 patients (age range 7-32 years). We used a sleep questionnaire to assess sleep and its disturbances quantitatively. To identify the periodicity in the diurnal rest-activity rhythms, the motor activity level was recorded by activity monitors continuously for a 1-week period with concomitant sleep logs. In addition, whole-night polysomnographic recordings were performed. The patients under 20 years of age had an excess of nocturnal sleep (the mean of the usual duration of nighttime sleep was 10.0 hours) and frequent daytime naps. Frequent shifts of the longest sleep period into the daytime hours and fragmented diurnal rest-activity patterns with no distinct rhythm occurred in the older patients. The progressive disease may damage the internal circadian timing system and also impair the ability of patients with variant late infantile neuronal ceroid lipofuscinosis to use external time cues for synchronization of their sleep and environmental time.

Parasomnias: co-occurrence and genetics.

In clinical practice, parasomnias are often found to run in families and to co-occur. Several studies have indicated a role of genetic factors in them. In 1990, a questionnaire (response rate, 77%) sent to the Finnish Twin Cohort, a representative population sample aged 33-60 years, surveyed the frequency of five parasomnias (sleepwalking, sleeptalking, enuresis, bruxism, and nightmares) in childhood and as adults. In assessing the phenotypic covariation and shared genetic effects between the parasomnias, we used polychoric correlations and structural equation modelling. In childhood (n = 5856 individuals), co-occurrence is highest in sleeptalking with sleepwalking (R = 0.73), nightmares (R = 0.50), and bruxism (R = 0.43). As adults (n = 8567), the results are similar (R = 0.56, 0.43, and 0.39, respectively). The analyses of shared genetic effects included 815 monozygotic and 1442 dizygotic twin pairs with complete responses on four parasomnias as adults. The strongest genetic covariation was found in sleeptalking with sleepwalking, sleeptalking with bruxism, and in sleeptalking with nightmares. The estimated proportions of shared genetic effects were 50, 30, and 26%, respectively. The present results indicate that parasomnias share some common genetic background.

Insufficient sleep--a population-based study in adults.

STUDY OBJECTIVES: Insufficient sleep (sleep deprivation) is a common problem of considerable health, social, and economical impact. We assessed its prevalence and associations, and the role of genetic influences. DESIGN: Panel study based on questionnaires administered in 1981 and 1990. SETTING/PATIENTS: 12.423 subjects aged 33-60 years included in the Finnish Twin Cohort, representative of the Finnish population. INTERVENTIONS: N/A. MEASUREMENTS: A difference of 1 hour between the self-reports of the sleep need and the sleep length was considered insufficient sleep. Associations with education, life style, work, psychological characteristics and sleep-wake variables were assessed. Structural equation modelling techniques were used to compare genetic models among monozygotic and dizygotic twin pairs. RESULTS: In 1990, the prevalence of insufficient sleep was 20.4% (16.2% in men and 23.9% in women). 44% of those with insufficient sleep in 1981 also had it 9 years later (Spearman correlation for persistence 0.334). In multivariate analyses, the strongest positively associated factors were daytime sleepiness (women: odds ratio 3.87, 95% confidence limits 3.24-4.63/men: 3.77, 2.98-4.75), insomnia (2.48, 1.92-3.19/2.91, 2.17-3.90), not able to sleep without disturbance (1.95, 1.47-2.60/2.54, 1.66-3.89), and evening type (2.10, 1.65-2.69/1.73, 1.25-2.41). Among men, also weekly working hours > or =75 was strongly associated (3.23, 1.54-6.78). "Not working" was negatively associated in both genders (0.68, 0.51-0.89/0.59, 0.42-0.83). Two thirds of the interindividual variability in the liability to insufficient sleep was attributed to non-genetic factors. CONCLUSIONS: Insufficient sleep is a common and long-standing condition, most strongly associated with sleep/wake variables. One third of the liability to it is attributed to genetic influences. Sleep sufficiency should be assesssed in health examinations of working adults.