Evolution of genetic networks for human creativity.

The genetic basis for the emergence of creativity in modern humans remains a mystery despite sequencing the genomes of chimpanzees and Neanderthals, our closest hominid relatives. Data-driven methods allowed us to uncover networks of genes distinguishing the three major systems of modern human personality and adaptability: emotional reactivity, self-control, and self-awareness. Now we have identified which of these genes are present in chimpanzees and Neanderthals. We replicated our findings in separate analyses of three high-coverage genomes of Neanderthals. We found that Neanderthals had nearly the same genes for emotional reactivity as chimpanzees, and they were intermediate between modern humans and chimpanzees in their numbers of genes for both self-control and self-awareness. 95% of the 267 genes we found only in modern humans were not protein-coding, including many long-non-coding RNAs in the self-awareness network. These genes may have arisen by positive selection for the characteristics of human well-being and behavioral modernity, including creativity, prosocial behavior, and healthy longevity. The genes that cluster in association with those found only in modern humans are over-expressed in brain regions involved in human self-awareness and creativity, including late-myelinating and phylogenetically recent regions of neocortex for autobiographical memory in frontal, parietal, and temporal regions, as well as related components of cortico-thalamo-ponto-cerebellar-cortical and cortico-striato-cortical loops. We conclude that modern humans have more than 200 unique non-protein-coding genes regulating co-expression of many more protein-coding genes in coordinated networks that underlie their capacities for self-awareness, creativity, prosocial behavior, and healthy longevity, which are not found in chimpanzees or Neanderthals.

Education as a moderator of genetic risk for higher body mass index: prospective cohort study from childhood to adulthood.

OBJECTIVES: The life-course development of body mass index (BMI) may be driven by interactions between genes and obesity-inducing social environments. We examined whether lower parental or own education accentuates the genetic risk for higher BMI over the life course, and whether diet and physical activity account for the educational differences in genetic associations with BMI. SUBJECTS/METHODS: The study comprised 2441 participants (1319 women, 3-18 years at baseline) from the prospective, population-based Cardiovascular Risk in Young Finns Study. BMI (kg/m2) trajectories were calculated from 18 to 49 years, using data from six time points spanning 31 years. A polygenic risk score for BMI was calculated as a weighted sum of risk alleles in 97 single-nucleotide polymorphisms. Education was assessed via self-reports, measured prospectively from participants in adulthood and from parents when participants were children. Diet and physical activity were self-reported in adulthood. RESULTS: Mean BMI increased from 22.6 to 26.6 kg/m2 during the follow-up. In growth curve analyses, the genetic risk score was associated with faster BMI increase over time (b=0.02, (95% CI, 0.01-0.02, P<0.001)). The association between the genetic risk score and BMI was more pronounced among those with lower educational level in adulthood (b=-0.12 (95% CI, -0.23-0.01); P=0.036)). No interaction effect was observed between the genetic risk score and parental education (b=0.05 (95% CI, -0.09-0.18; P=0.51)). Diet and physical activity explained little of the interaction effect between the genetic risk score and adulthood education. CONCLUSIONS: In this prospective study, the association of a risk score of 97 genetic variants with BMI was stronger among those with low compared with high education. This suggests lower education in adulthood accentuates the risk of higher BMI in people at genetic risk.

Work stress, poor recovery and burnout in teachers.

BACKGROUND: Both work stress and poor recovery have been shown to contribute to the development of burnout. However, the role of recovery as a mediating mechanism that links work stress to burnout has not been sufficiently addressed in research. AIMS: To examine recovery as a mediator in the relationship between work stress and burnout among teachers. METHODS: A cross-sectional study of Finnish primary school teachers, in whom burnout was measured with the Maslach Burnout Inventory-General Survey and work stress was conceptualized using the effort-reward imbalance (ERI) model. Recovery was measured with the Recovery Experience Questionnaire and the Jenkins Sleep Problems Scale. Multiple linear regression analyses and bootstrap mediation analyses adjusted for age, gender and total working hours were performed. RESULTS: Among the 76 study subjects, high ERI was associated with burnout and its dimensions of exhaustion, cynicism and reduced professional efficacy. Poor recovery experiences, in terms of low relaxation during leisure time, partially mediated the relationship between ERI and reduced professional efficacy. Sleep problems, in the form of non-restorative sleep, partially mediated the relationship between ERI and both burnout and exhaustion. CONCLUSIONS: Supporting a balance between effort and reward at work may enhance leisure time recovery and improve sleep quality, as well as help to reduce burnout rates.

Associations of temporal and energetic characteristics of behavior with depressive symptoms: A population-based longitudinal study within Strelau's Regulative Theory of Temperament.

BACKGROUND: Individual dispositions have previously been associated with increased risk for depressive symptoms. The direction of the association has been found to be sometimes reciprocal. We examined whether temperament traits are associated with depressive symptoms and whether depressive symptoms contribute to changes in temperament. METHODS: Participants (n=674-811) were from a population-based Young Finns Study. Temperament was assessed by a Finnish version of the Formal Characteristics of Behavior - Temperament Inventory. Depressive symptoms were assessed with modified BDI (mBDI) in 1997, 2001, 2007 and 2012, and BDI-II in 2012. RESULTS: Higher perseveration and emotional reactivity were associated with higher level of depressive symptoms, and higher endurance was associated with lower level of depressive symptoms in 2007 and 2012. These associations were independent of several potential confounders and baseline depressive symptoms. The results of cross-lagged structural equation modeling showed that the associations between temperament and depressive symptoms were reciprocal: briskness, endurance and activity decreased the risk for depressive symptoms while depressive symptoms decreased the level of these characteristics. Perseveration, emotional reactivity and depressive symptoms reinforced each other over time. LIMITATIONS: The depressive symptoms scales we used are not meant for measuring clinically diagnosed depression. The relationships between temperament traits and depressive symptoms were not strong enough to provide a clinical basis for guiding treatment. CONCLUSIONS: Lower perseveration, lower emotional reactivity and higher endurance seem to be health protective temperament characteristics that reduce the risk for depressive symptoms. The reciprocal associations between temperament and depressive symptoms imply mutual health protective and health declining effects. Clinical relevance of the study is that enhancing positive loops and self-concept, and supporting individual stress management might be helpful in prevention of depressive symptoms.

Depressive symptoms are associated with lower bone mineral density in young adults with high job strain. The Cardiovascular Risk in Young Finns Study.

BACKGROUND: Job strain has been associated with depressive symptoms, and depression has been associated with low bone mineral density (BMD). PURPOSE: The associations between BMD and job strain have not been studied. We examined the relations between BMD, job strain, and depressive symptoms in a population-based group of young adults in Finland. METHOD: Ultrasonic measurement of BMD at the calcaneus was performed on 777 participants (men 45 %, aged 30-45) drawn from the Cardiovascular Risk in Young Finns Study. Job strain was assessed by self-administered questionnaires by the combination of job demands and job control. Depressive symptoms were assessed with a modified Beck Depression Inventory. The effects of job strain on BMD were studied with multivariable analyses with age, sex, BMI, vitamin D, and calcium intake, physical activity, cigarette smoking, alcohol use, and depressive symptoms as covariates. RESULTS: Depressive symptoms were independently associated with lower BMD T score in participants with high job strain (ß = -0.241, p = 0.02), but depressive symptoms were not significantly associated with BMD in the low (ß = -0.160, p = 0.26) and intermediate (ß = -0.042, p = 0.66) job strain categories. CONCLUSION: The results suggest that job strain modifies the association between depressive symptoms and BMD. Depressed individuals with high work-related stress might be in increased risk of lower bone mineral density.

Work stress and the long QT syndrome: high job strain and effort-reward imbalance at work associated with arrhythmic risk in the long QT syndrome.

OBJECTIVES: To examine whether work stress is associated with a symptomatic status of the long QT syndrome (LQTS). METHODS: The sample comprised 173 KCNQ1, KCNH2, or SCN5A gene mutation carriers (70 symptomatic) and control groups of 203 relatives without the family mutation, and of 1209 population-based young Finns control subjects. Work stress was assessed using the Job Content Questionnaire and Occupational Stress Questionnaire. RESULTS: We found an association between the occurrence of symptoms in the LQTS and high work stress, higher job demands/effort, lower job control, and lower rewards compared with control subjects. We also found that symptomatic LQTS mutation carriers had higher work stress than asymptomatic LQTS mutation carriers. CONCLUSIONS: Higher work stress is related to arrhythmic risk in the LQTS. It may be useful to incorporate assessment of work conditions and stress interventions into management of high-risk patients.

Childhood family factors predict developmental trajectories of hostility and anger: a prospective study from childhood into middle adulthood.

BACKGROUND: Low socio-economic status (SES), and a conflictive, cold and unsupportive family environment in childhood have been associated with early adulthood hostility. However, it is unknown whether this association changes in magnitude with age from childhood to adulthood. We investigated whether childhood family factors (SES and parental child-rearing style) predicted differential development of offspring hostility and anger from early to middle adulthood. METHOD: Between 2041 and 2316 participants (age range 3-18 years at baseline) were selected from the longitudinal Young Finns study. The participants were followed for 27 years between 1980 and 2007. Childhood SES and parent's self-reported child-rearing style were measured twice: at baseline and 3 years after baseline. Hostility and anger were assessed with self-report questionnaires at 12, 17, 21 and 27 years after baseline. RESULTS: Low parental SES and hostile child-rearing style at baseline predicted higher mean levels of offspring anger and hostility. Low parental SES and one of the hostile child-rearing style components (strict disciplinary style) became more strongly associated with offspring hostility with age, suggesting an accumulating effect. CONCLUSIONS: Childhood family factors predict the development of hostility and anger over 27 years and some of these family factors have a long-term accumulating effect on the development of hostility.

Longitudinal course of depressive symptoms in adulthood: linear stochastic differential equation modeling.

BACKGROUND: Although many studies have addressed the topic of stability versus change in depressive symptoms, few have further decomposed the change to continuous accumulation versus non-systematic state fluctuations or measurement errors. This further step requires a longitudinal follow-up and an appropriate stochastic model; it would, for example, evaluate the hypothesis that women accumulate more susceptibility events than men. Method A linear stochastic differential equation model was estimated for a 16-year longitudinal course of depressive symptoms in the Young Finns community sample of 3596 participants (1832 women, 1764 men). This model enabled us to decompose the variance in depression symptoms into a stable trait, cumulative effects and state/error fluctuations. RESULTS: Women showed higher mean levels and higher variance of depressive symptoms than men. In men, the stable trait accounted for the majority [61%, 90% confidence interval (CI) 48.9-69.2] of the total variance, followed by cumulative effects (23%, 90% CI 9.9-41.7) and state/error fluctuations (16%, 90% CI 5.6-23.2). In women, the cumulative sources were more important than among men and accounted for 44% (90% CI 23.6-58.9) of the variance, followed by stable individual differences (32%, 90% CI 18.5-54.2) and state fluctuations (24%, 90% CI 19.1-27.3). CONCLUSIONS: The results are consistent with previous observations that women suffer more depression than men, and have more variance in depressive symptoms. We also found that continuously accumulating effects are a significant contributor to between-individual differences in depression, especially for women. Although the accumulating effects are often confounded with non-systematic state fluctuations, the latter are unlikely to exceed 27% of the total variance of depressive symptoms.

Temperament, character and serotonin activity in the human brain: a positron emission tomography study based on a general population cohort.

BACKGROUND: The psychobiological model of personality by Cloninger and colleagues originally hypothesized that interindividual variability in the temperament dimension 'harm avoidance' (HA) is explained by differences in the activity of the brain serotonin system. We assessed brain serotonin transporter (5-HTT) density in vivo with positron emission tomography (PET) in healthy individuals with high or low HA scores using an 'oversampling' study design. Method Subjects consistently in either upper or lower quartiles for the HA trait were selected from a population-based cohort in Finland (n = 2075) with pre-existing Temperament and Character Inventory (TCI) scores. A total of 22 subjects free of psychiatric and somatic disorders were included in the matched high- and low-HA groups. The main outcome measure was regional 5-HTT binding potential (BPND) in high- and low-HA groups estimated with PET and [11C]N,N-dimethyl-2-(2-amino-4-methylphenylthio)benzylamine ([11C]MADAM). In secondary analyses, 5-HTT BPND was correlated with other TCI dimensions. RESULTS: 5-HTT BPND did not differ between high- and low-HA groups in the midbrain or any other brain region. This result remained the same even after adjusting for other relevant TCI dimensions. Higher 5-HTT BPND in the raphe nucleus predicted higher scores in 'self-directedness'. CONCLUSIONS: This study does not support an association between the temperament dimension HA and serotonin transporter density in healthy subjects. However, we found a link between high serotonin transporter density and high 'self-directedness' (ability to adapt and control one's behaviour to fit situations in accord with chosen goals and values). We suggest that biological factors are more important in explaining variability in character than previously thought.

Neuropeptide Y polymorphism increases the risk for asthma in overweight subjects; protection from atherosclerosis in asthmatic subjects--the cardiovascular risk in young Finns study.

AIMS: The role of neuropeptide Y (NPY) and its gene polymorphisms in the development of atherosclerosis has become increasingly evident. In asthma, NPY has been shown to be involved as immunomodulator. In this study, we investigated the role of two functional NPY polymorphisms, NPY-Leu7Pro (rs16139) and NPY-399C/T (rs16147) and obesity for the development of asthma as well as atherosclerosis in asthmatic and non-asthmatic subjects. Also, we measured heart rate variability (HRV) and NPY in serum since these might contribute through these polymorphisms to both diseases. METHODS AND RESULTS: Thousand hundred and seventy six Finnish young adults were genotyped and three groups (G1-G3) were formed based on the observed diplotypes. The NPY-Pro7 allele always co-existed with the NPY-399T allele indicating complete linkage disequilibrium. Here we show that overweight (BMI≥25kg/m2) was associated with 2.5-fold increased risk for asthma in subjects with the NPY-399T allele without NPY-Pro7 allele (G2, n=716). Overweight was also associated with increased atherosclerosis determined by carotid intima media thickness (cIMT), but asthma seemed to be more significant determinant than overweight in determing cIMT having a decreasing effect. NPY concentration in serum was diplotype-driven (G1=792.2(29.5), G2=849.0(18.9), G3=873.9(45.2) pg/ml) and correlated positively with cIMT in the group having NPY-Pro7 allele (G3, n=142). However, the subjects with asthma had a negative NPY-cIMT relationship. Total HRV was increased in asthma and correlated negatively with cIMT irrespective of the NPY genotype. CONCLUSIONS: Overweight together with the NPY-399T allele without NPY-Pro7 allele was associated with increased risk for asthma. Atherosclerosis was decreased in subjects with asthma depending on the NPY genotype. The results reveal novel insights into the genetics and biology of the relationship of atherosclerosis and asthma.

Body mass index and depressive symptoms: instrumental-variables regression with genetic risk score.

The causal role of obesity in the development of depression remains uncertain. We applied instrumental-variables regression (Mendelian randomization) to examine the association of adolescent and adult body mass index (BMI) with adult depressive symptoms. Participants were from the Young Finns prospective cohort study (n = 1731 persons, 2844 person-observations), with repeated measurements of BMI and depressive symptoms (modified Beck's Depression Inventory). Genetic risk score of 31 single nucleotide polymorphisms previously identified as robust genetic markers of body weight was used as a proxy for variation in BMI. In standard linear regression analysis, higher adult depressive symptoms were predicted by higher adolescent BMI (B = 0.33, CI = 0.06-0.60, P = 0.017) and adult BMI (B = 0.47, CI = 0.32-0.63, P < 0.001). These associations were replicated in instrumental-variables analysis with genetic risk score as instrument (B = 1.96, CI = 0.03-3.90, P = 0.047 for adolescent BMI; B = 1.08, CI = 0.11-2.04, P = 0.030 for adult BMI). The association for adolescent BMI was significantly stronger in the instrumented analysis compared to standard regression (P = 0.04). These findings provide additional evidence to support a causal role for high BMI in increasing symptoms of depression. However, the present analysis also demonstrates potential limitations of applying Mendelian randomization when using complex phenotypes.

A genome-wide meta-analysis of association studies of Cloninger's Temperament Scales.

Temperament has a strongly heritable component, yet multiple independent genome-wide studies have failed to identify significant genetic associations. We have assembled the largest sample to date of persons with genome-wide genotype data, who have been assessed with Cloninger's Temperament and Character Inventory. Sum scores for novelty seeking, harm avoidance, reward dependence and persistence have been measured in over 11,000 persons collected in four different cohorts. Our study had >80% power to identify genome-wide significant loci (P<1.25 × 10(-8), with correction for testing four scales) accounting for ≥0.4% of the phenotypic variance in temperament scales. Using meta-analysis techniques, gene-based tests and pathway analysis we have tested over 1.2 million single-nucleotide polymorphisms (SNPs) for association to each of the four temperament dimensions. We did not discover any SNPs, genes, or pathways to be significantly related to the four temperament dimensions, after correcting for multiple testing. Less than 1% of the variability in any temperament dimension appears to be accounted for by a risk score derived from the SNPs showing strongest association to the temperament dimensions. Elucidation of genetic loci significantly influencing temperament and personality will require potentially very large samples, and/or a more refined phenotype. Item response theory methodology may be a way to incorporate data from cohorts assessed with multiple personality instruments, and might be a method by which a large sample of a more refined phenotype could be acquired.

Serotonin receptor 2A gene moderates the effect of childhood maternal nurturance on adulthood social attachment.

The ability to form and maintain attachment relations with other people is crucial for mental health and well-being. The origins of attachment behaviors are often assumed to be in early experiences with other people, especially with primary caregivers. Preliminary evidence suggests that serotonergic system may be involved in attachment behaviors. We examined whether the T102C variant of the serotonin receptor 2A gene moderates the effect of childhood maternal nurturance on social attachment in adulthood. The participants were 1070 women and men from the Young Finns Study with 27-year follow-up and two measurement times for the outcomes (n = 1836 person observations). Mothers reported their relationship quality with their children (participants) in childhood or adolescence. Social attachment was assessed by participant's self-reports on two measures (reward dependence scale of the Temperament and Character Inventory and the Relationship Questionnaire). High childhood maternal nurturance predicted high reward dependence and low avoidant attachment in carriers of the T/T genotype but not in the T/C or C/C genotype groups, while low maternal nurturance was associated with low reward dependence and high avoidant attachment in T/T genotype carriers but not in C allele carriers. Our result suggests that T/T genotype carriers were more influenced by their childhood nurturing environment, than their C allele carrying counterparts, thus providing evidence for differential susceptibility to childhood nurturing environment associated with the HTR2A gene.

Hostility in adolescents and adults: a genome-wide association study of the Young Finns.

Hostility is a multidimensional personality trait with changing expression over the life course. We performed a genome-wide association study (GWAS) of the components of hostility in a population-based sample of Finnish men and women for whom a total of 2.5 million single-nucleotide polymorphisms (SNPs) were available through direct or in silico genotyping. Hostility dimensions (anger, cynicism and paranoia) were assessed at four time points over a 15-year interval (age range 15-30 years at phase 1 and 30-45 years at phase 4) in 982-1780 participants depending on the hostility measure. Few promising areas from chromosome 14 at 99 cM (top SNPs rs3783337, rs7158754, rs3783332, rs2181102, rs7159195, rs11160570, rs941898, P values <3.9 × 10(-8) with nearest gene Enah/Vasp-like (EVL)) were found suggestively to be related to paranoia and from chromosome 7 at 86 cM (top SNPs rs802047, rs802028, rs802030, rs802026, rs802036, rs802025, rs802024, rs802032, rs802049, rs802051, P values <6.9 × 10(-7) with nearest gene CROT (carnitine O-octanoyltransferase)) to cynicism, respectively. Some shared suggestive genetic influence for both paranoia and cynicism was also found from chromosome 17 at 2.8 cM (SNPs rs12936442, rs894664, rs6502671, rs7216028) and chromosome 22 at 43 cM (SNPs rs7510759, rs7510924, rs7290560), with nearest genes RAP1 GTPase activating protein 2 (RAP1GAP2) and KIAA1644, respectively. These suggestive associations did not replicate across all measurement times, which warrants further study on these SNPs in other populations.

Sustained involvement in youth sports activities predicts reduced chronic job strain in early midlife.

OBJECTIVE: We examined the long-term effects of youth leisure time physical activity (LTPA) and sports participation on the prevalence of chronic work stress in adulthood. METHODS: Participants (326 men and 338 women) aged 9 to 18 years were initially enrolled in 1980 and followed until 2007. Data were collected using questionnaires and bicycle ergometry in a subgroup. RESULTS: High youth LTPA and sports participation predicted lower chronic job strain in both sexes. The association was mediated by type A leadership. Participation and persistence in organized youth sports followed a similar pattern. In the subgroup, adult physical fitness only partly accounted for the association. CONCLUSIONS: Sustained involvement in youth physical activity and sport lasting at least 3 years is associated with reduced chronic job strain in adulthood. The association was partially explained by type A leadership and physical fitness.

A prospective cohort study of deficient maternal nurturing attitudes predicting adulthood work stress independent of adulthood hostility and depressive symptoms.

Stressful childhood environments arising from deficient nurturing attitudes are hypothesized to contribute to later stress vulnerability. We examined whether deficient nurturing attitudes predict adulthood work stress. Participants were 443 women and 380 men from the prospective Cardiovascular Risk in Young Finns Study. Work stress was assessed as job strain and effort-reward imbalance in 2001 when the participants were from 24 to 39 years old. Deficient maternal nurturance (intolerance and low emotional warmth) was assessed based on mothers' reports when the participants were at the age of 3-18 years and again at the age of 6-21 years. Linear regressions showed that deficient emotional warmth in childhood predicted lower adulthood job control and higher job strain. These associations were not explained by age, gender, socioeconomic circumstances, maternal mental problems or participant hostility, and depressive symptoms. Deficient nurturing attitudes in childhood might affect sensitivity to work stress and selection into stressful work conditions in adulthood. More attention should be paid to pre-employment factors in work stress research.

A history of stressful life events, prolonged mental stress and arrhythmic events in inherited long QT syndrome.

OBJECTIVE: To examine whether a history of stressful life events and prolonged mental stress are associated with arrhythmic events in inherited long QT syndrome (LQTS). METHODS: Participants who had a molecularly established mutation of KCNQ1, KCNH2 or SCN5A channel and were thus diagnosed as patients with LQT1, LQT2 and LQT3 (n=566), accordingly. The control group consisted of their 614 non-affected relatives. A history of stressful life events was indexed by the major stressful life events. Prolonged mental stress was indexed by vital exhaustion (VE), which was measured with the Maastricht Questionnaire. RESULTS: Multinomial logistic regression analysis including patients with LQTS with and without arrhythmic events and the control subjects showed an age- and sex-adjusted association of stressful life events OR=1.15 (95% CI 1.08 to 1.22) and VE (OR=3.33 (95% CI 1.63 to 6.78)) with symptomatic status of LQTS. Symptomatic patients with LQTS had experienced more stressful life events (OR=1.16 (95% CI 1.08 to 1.24)) and the level of VE (OR=3.40 (95% CI 1.44 to 8.03)) was more than three times higher among patients with LQTS with arrhythmic events than in asymptomatic LQTS mutation carriers. The association between stressful life events and arrhythmic events was independent of age, sex, specifically focused medication and LQTS subtype. CONCLUSIONS: A history of stressful life events and prolonged mental stress are associated with arrhythmic events in LQTS in this large sample of molecularly defined patients with LQTS. It is important for future studies to assess how strong these predisposing factors are for arrhythmic events in LQTS.

Does genetic background moderate the association between parental education and school achievement?

This study was conducted with a purpose to examine whether the T102C polymorphism of the serotonin receptor 2A (HTR2A) gene moderates the association between parental education and children's school achievement across nine compulsory school years. The study was carried out in a population-based sample of Finnish students (aged 9, 12 and 15 years, n = 982). It was found that the HTR2A gene was not related to the school achievement at any school level, but moderated the association between maternal education and the children's grade point averages. The T/T genotype carriers benefited most from high-maternal education, and suffered from a low one more than the carriers of the other variants of the HTR2A gene. The present finding may at least partly answer the important question why academic outcomes of environmental interventions vary even at the same intelligence levels of the students.

Metabolic syndrome and short-term heart rate variability in young adults. The cardiovascular risk in young Finns study.

AIMS: Heart rate variability (HRV) can be used to estimate autonomic nervous control of the cardiovascular system. In middle-aged subjects, the metabolic syndrome (MetS) is associated with lower HRV. We hypothesized that alterations in autonomic balance are already present in young adults with the MetS, and analysed the association of short-term HRV with the MetS (using the National Cholesterol Education Program definition), in 1889 subjects aged 24-39 years. METHODS: Short-term (3 min) HRV analysis included high-frequency (HF), low-frequency (LF) and total (TP) spectral components of HRV and LF/HF ratio. RESULTS: The presence of the MetS was associated with lower HF, LF and TP in men and women, and with higher LF/HF ratio in women. In men, waist circumference was the strongest individual MetS component that associated with HRV. After adjustments for age and heart rate, MetS was associated with lower HF and higher LF/HF ratio in women, but only with a lower TP in men (all P < 0.05). CONCLUSIONS: MetS is associated with lower HRV in young adults. The individual components of MetS are differentially associated with HRV in men and in women. Our results are consistent with lower vagal activity and a possible increase in sympathetic predominance in women with the MetS. This sex difference in vagal activity and sympathovagal balance may partly explain the greater increase in cardiovascular risk associated with MetS in women than in men.

Sickness absence among female employees with migraine and co-existing conditions.

This prospective cohort study examined the risk of sickness absence among 27,127 female public-sector employees by status of migraine and co-existing conditions. A baseline survey was used to assess chronic disorders and demographic factors. Information on sickness absence in the 3 years following the survey was obtained from employers' registers. Migraine was related to 5.4 extra sickness absence days per person-year, with the corresponding figures being 14.6 and 6.1 for depression and respiratory disorders, respectively. After adjusting for age, marital status, socioeconomic status and presence of depression or respiratory disorders, employees with migraine had a 1.21 (95% confidence interval 1.18, 1.24) times higher risk of self-certified sickness absence episodes (< or = 3 days) than did those without migraine. The corresponding excess risk for medically certified absence episodes (> 3 days) was 1.15 (1.12, 1.19). Among employees with depression or respiratory disorders, secondary migraine was associated with an increased risk of sickness absence episode of 1.15 to 1.23. These findings suggest that migraine is associated with increased risk of recorded sickness absence independent of depression and respiratory disorders.