Association between area deprivation and major depressive disorder in British men and women: a cohort study.

OBJECTIVE: Studies have shown area-level deprivation can increase the risk for mental disorders over and above individual-level circumstances, such as education and social class. The objective of this study is to determine whether area deprivation is associated with major depressive disorder (MDD) in British women and men separately while adjusting for individual-level factors. DESIGN: Large, population study. SETTING: UK population-based cohort. PARTICIPANTS: 30 445 people from the general population aged 40 years and older and living in England consented to participate at study baseline, and of these, over 20 000 participants completed a structured Health and Life Experiences Questionnaire used to capture MDD. Area deprivation was measured in 1991 using Census data, and current MDD was assessed in 1996-2000. 8236 men and 10 335 women had complete data on all covariates. PRIMARY OUTCOME MEASURE: MDD identified according to the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV). RESULTS: In this study, 3.3% (339/10 335) of women and 2.1% (177/8236) of men had MDD. Men living in the most deprived areas were 51% more likely to have depression than those living in areas that were not deprived (OR=1.51, 95% CI 1.01 to 2.24; p=0.043), but the association between deprivation and MDD was not statistically significant in women (OR=1.24, 95% CI 0.93 to 1.65; p=0.143). CONCLUSION: This study shows that the residential environment differentially affects men and women, and this needs to be taken into account by mental health policy-makers. Knowing that men living in deprived conditions are at high risk for having depression helps inform targeted prevention and intervention programmes.

Sex differences in the association between area deprivation and generalised anxiety disorder: British population study.

OBJECTIVE: Studies have shown that area-level deprivation measured by factors, such as non-home ownership, non-car ownership and household overcrowding, can increase the risk for mental disorders over and above individual-level circumstances, such as education and social class. Whether area-level deprivation is associated with generalised anxiety disorder (GAD) independent of personal circumstances, and whether this association is different between British women and men is unknown. DESIGN: Large, population study. SETTING: UK population-based cohort. PARTICIPANTS: 30 445 people from the general population aged 40 years and older and living in England consented to participate at study baseline, and of these, 21 921 participants completed a structured health and lifestyle questionnaire used to capture GAD. Area deprivation was measured in 1991 using Census data, and GAD was assessed in 1996-2000. 10 275 women and 8219 men had complete data on all covariates. MAIN OUTCOME MEASURE: Past-year GAD defined according to the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV). RESULTS: In this study, 2.5% (261/10 275) of women and 1.8% (145/8219) of men had GAD. Women living in the most deprived areas were over 60% more likely to develop anxiety than those living in areas that were not deprived (OR=1.63, 95% CI 1.21 to 2.21; p=0.001), but this association between deprivation and GAD was not apparent in men (OR=1.13, 95% CI 0.72 to 1.77; p=0.598). CONCLUSIONS: The absolute numbers of people living in deprived conditions are large worldwide. This, combined with a growing mental health burden, means that the findings obtained in this study remain highly relevant. The WHO has emphasised the need to reduce social and health inequalities. Our findings provide a strong evidence base to this call, showing that the environment needs to be taken into account when developing mental health policy; gender is important when it comes to assessing the influence of the environment on our mental health.

Daytime napping and increased risk of incident respiratory diseases: symptom, marker, or risk factor?

BACKGROUND: We have identified a strong association between daytime napping and increased mortality risk from respiratory diseases, but little is known about the relationship between daytime napping and respiratory morbidity. METHODS: Data were drawn from the European Prospective Investigation into Cancer and Nutrition-Norfolk cohort. Participants reported napping habits during 1998-2000 and were followed up for respiratory disease hospital admissions until March 2009. Cox proportional hazards regression was used to examine the association between daytime napping and respiratory disease incidence risk. RESULTS: The study sample included 10,978 men and women with a mean age of 61.9 years, and a total of 946 incident respiratory disease cases were recorded. After adjustment for age, sex, social class, education, marital status, employment status, nightshift work, body mass index, physical activity, smoking, alcohol intake, self-reported general health, hypnotic drug use, habitual sleep duration, and preexisting health conditions, daytime napping was associated with an increase in the overall respiratory disease incidence risk (hazard ratio (HR) = 1.32, 95% confidence interval (CI) 1.15, 1.52 for napping <1 h; HR = 1.54, 95% CI 1.14, 2.09 for napping ≥1 h). This association was more pronounced for lower respiratory diseases, especially for the risk of chronic lower respiratory diseases (HR = 1.52, 95% CI: 1.18, 1.96 for napping <1 h; HR = 1.72, 95% CI: 1.01, 2.92 for napping ≥1 h, overall p = 0.003). CONCLUSIONS: Excessive daytime napping might be a useful marker of future respiratory disease incidence risk. Further studies are required to confirm these findings and help understand potential mechanisms.

Sleep duration and risk of fatal and nonfatal stroke: a prospective study and meta-analysis.

OBJECTIVE: To study the association between sleep duration and stroke incidence in a British population and to synthesize our findings with published results through a meta-analysis. METHODS: The prospective study included 9,692 stroke-free participants aged 42-81 years from the European Prospective Investigation into Cancer-Norfolk cohort. Participants reported sleep duration in 1998-2000 and 2002-2004, and all stroke cases were recorded until March 31, 2009. For the meta-analysis, we searched Ovid Medline, EMBASE, and the Cochrane Library for prospective studies published until May 2014, and pooled effect estimates using a weighted random-effect model. RESULTS: After 9.5 years of follow-up, 346 cases of stroke occurred. Long sleep was significantly associated with an increased risk of stroke (hazard ratio [HR] = 1.46 [95% confidence interval (CI) 1.08, 1.98]) after adjustment for all covariates. The association remained robust among those without preexisting diseases and those who reported sleeping well. The association for short sleep was smaller (and not statistically significant) (HR = 1.18 [95% CI 0.91, 1.53]). There was a higher stroke risk among those who reported persistently long sleep or a substantial increase in sleep duration over time, compared to those reporting persistently average sleep. These were compatible with the pooled HRs from an updated meta-analysis, which were 1.15 (1.07, 1.24) and 1.45 (1.30, 1.62) for short and long sleep duration, respectively. CONCLUSIONS: This prospective study and meta-analysis identified prolonged sleep as a potentially useful marker of increased future stroke risk in an apparently healthy aging population.

Daytime napping, sleep duration and serum C reactive protein: a population-based cohort study.

OBJECTIVES: To explore whether daytime napping and sleep duration are linked to serum C reactive protein (CRP), a pro-inflammatory marker, in an older aged British population. DESIGN: Cross-sectional study. SETTING: European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk study. PARTICIPANTS: A total of 5018 men and women aged 48-92 years reported their sleep habits and had serum CRP levels measured. OUTCOME AND MEASURES: CRP was measured (mg/L) during 2006-2011 in fresh blood samples using high-sensitivity methods. Participants reported napping habits during 2002-2004, and reported sleep quantity during 2006-2007. Multivariable linear regression models were used to examine the association between napping and log-transformed CRP, and geometric mean CRP levels were calculated. RESULTS: After adjustment for age and sex, those who reported napping had 10% higher CRP levels compared with those not napping. The association was attenuated but remained borderline significant (ß=0.05 (95% CI 0.00 to 0.10)) after further adjustment for social class, education, marital status, body mass index, physical activity, smoking, alcohol intake, self-reported health, pre-existing diseases, systolic blood pressure, hypnotic drug use, depression and in women-only hormone replacement therapy use. The geometric means (95% CI) of CRP levels were 2.38 (2.29 to 2.47) mg/L and 2.26 (2.21 to 2.32) mg/L for those who reported napping and no napping, respectively. A U-shaped association was observed between time spent in bed at night and CRP levels, and nighttime sleep duration was not associated with serum CRP levels. The association between napping and CRP was stronger for older participants, and among extremes of time spent in bed at night. CONCLUSIONS: Daytime napping was associated with increased CRP levels in an older aged British population. Further studies are needed to determine whether daytime napping is a cause for systemic inflammation, or if it is a symptom or consequence of underlying health problems.

Daytime napping and the risk of all-cause and cause-specific mortality: a 13-year follow-up of a British population.

Epidemiologic studies have reported conflicting results on the relationship between daytime napping and mortality risk, and there are few data on the potential association in the British population. We investigated the associations between daytime napping and all-cause or cause-specific mortality in the European Prospective Investigation Into Cancer-Norfolk study, a British population-based cohort study. Among the 16,374 men and women who answered questions on napping habits between 1998 and 2000, a total of 3,251 died during the 13-year follow-up. Daytime napping was associated with an increased risk of all-cause mortality (for napping less than 1 hour per day on average, hazard ratio = 1.14, 95% confidence interval: 1.02, 1.27; for napping 1 hour or longer per day on average, hazard ratio = 1.32, 95% confidence interval: 1.04, 1.68), independent of age, sex, social class, educational level, marital status, employment status, body mass index, physical activity level, smoking status, alcohol intake, depression, self-reported general health, use of hypnotic drugs or other medications, time spent in bed at night, and presence of preexisting health conditions. This association was more pronounced for death from respiratory diseases (for napping less than 1 hour, hazard ratio = 1.40, 95% confidence interval: 0.95, 2.05; for napping 1 hour or more, hazard ratio = 2.56, 95% confidence interval: 1.34, 4.86) and in individuals 65 years of age or younger. Excessive daytime napping might be a useful marker of underlying health risk, particularly of respiratory problems, especially among those 65 years of age or younger. Further research is required to clarify the nature of the observed association.

Self-reported sleep patterns in a British population cohort.

OBJECTIVES: Sleep patterns have been linked to various health outcomes, but sleep patterns in the British population have not been extensively reported. We aimed to describe the sleep characteristics reported by the European Prospective Investigation of Cancer (EPIC)-Norfolk participants, with a particular emphasis on the comparison of measures of sleep quantity. METHODS: From 2006 to 2007, a total of 8480 participants aged 45-90 years reported sleep timing, nighttime sleep duration, and sleep difficulties. Time in bed (TIB) was calculated from the difference between rise time and bedtime, and sleep proportion was defined as the ratio of sleep duration and TIB. RESULTS: On average, the reported TIB was more than 1.5h longer than sleep durations. Compared to men, women spent 15 min longer in bed, but they slept for 11 min less and reported more sleep difficulties. In multivariate analysis sleep duration and TIB varied with socioeconomic factors, but sleep proportion was consistently lower among women, nonworkers, and older individuals, as well as those who were widowed, separated, or divorced; those who reported sleep difficulties and more frequently used sleep medication; and those who had lower education, poorer general health, or a major depressive disorder (MDD). CONCLUSIONS: Self-reported sleep duration and TIB have different meanings and implications for health. Sleep proportion may be a useful indicator of sleep patterns in the general population.

Changes in HDL cholesterol and cardiovascular outcomes after lipid modification therapy.

BACKGROUND: Lipid modification therapy (LMT) produces cardiovascular benefits principally through reductions in low density lipoprotein cholesterol. While recent evidence, using data from 454 participants in the Framingham Offspring Study, has suggested that increases in high density lipoprotein cholesterol (HDL-C) are also associated with a reduction in cardiovascular outcomes, independently of changes in low density lipoprotein cholesterol, replication of this finding is important. The authors therefore present further results using data from the EPIC-Norfolk (UK) and Rotterdam (The Netherlands) prospective cohort studies. METHODS: A total of 1148 participants, 446 from the EPIC-Norfolk and 702 from the Rotterdam study, were assessed for lipids before and after starting LMT. Subsequent risk of cardiovascular events, ascertained through linkage with mortality records and hospital databases, was investigated using Cox proportional hazards regression. Random effects meta-analysis was used to combine results across studies. RESULTS: Based on combined data from the EPIC-Norfolk and Rotterdam studies there was some evidence that change in HDL-C resulting from LMT was associated with reduced cardiovascular risk (HR per pooled SD (=0.34 mmol/l) increase=0.74, 95% CI 0.56 to 0.99, adjusted for age, sex and baseline HDL-C). However, this association was attenuated and was not (statistically) significant with further adjustments for non-HDL-C and for cigarette smoking history, prevalent diabetes, systolic blood pressure, body mass index, use of antihypertensive medication, previous myocardial infarction, prevalent angina and previous stroke (0.92, 0.701.20). CONCLUSIONS: Following adjustment for conventional non-lipid risk factors of cardiovascular disease, this study provides no evidence to support a significant benefit from increasing HDL-C independent of the effect of lowering non-HDL-C.

Meta analysis of candidate gene variants outside the LPA locus with Lp(a) plasma levels in 14,500 participants of six White European cohorts.

BACKGROUND: Both genome-wide association studies and candidate gene studies have reported that the major determinant of plasma levels of the Lipoprotein (a) [Lp(a)] reside within the LPA locus on chromosome 6. We have used data from the HumanCVD BeadChip to explore the contribution of other candidate genes determining Lp(a) levels. METHODS: 48,032 single nucleotide polymorphisms (SNPs) from the Illumina HumanCVD BeadChip were genotyped in 5059 participants of the Whitehall II study (WHII) of randomly ascertained healthy men and women. SNPs showing association with Lp(a) levels of p<10(-4) outside the LPA locus were selected for replication in a total of an additional 9463 participants of five European based studies (EAS, EPIC-Norfolk, NPHSII, PROCARDIS, and SAPHIR). RESULTS: In Whitehall II, apart from the LPA locus (where p values for several SNPs were <10(-30)) there was significant association at four loci GALNT2, FABP1, PPARGC1A and TNFRSFF11A. However, a meta-analysis of the six studies did not confirm any of these findings. CONCLUSION: Results from this meta analysis of 14,522 participants revealed no candidate genes from the HumanCVD BeadChip outside the LPA locus to have an effect on Lp(a) levels. Further studies with genome-wide and denser SNP coverage are required to confirm or refute this finding.

The Val66Met coding variant of the brain-derived neurotrophic factor (BDNF) gene does not contribute toward variation in the personality trait neuroticism.

BACKGROUND: The val66met variant located within the brain-derived neurotrophic factor gene (BDNF) has previously been associated with human neuroticism, a dimension of personality strongly predictive of depressive illness. METHODS: Here we report an attempt to replicate this association using three populations of extreme neuroticism scorers derived from two large English cohorts (n = 88,142 and n = 20,921). On the basis of the current literature, which indicates that an effect of BDNF may only become apparent in those individuals exposed to stress, a gene-environment interaction was also sought. RESULTS: No statistically significant effects were identified, although simulations indicated that the samples held sufficient power to detect a main effect accounting for just .75% of variation and an interaction accounting for 4% of variation. CONCLUSIONS: These data do not support the hypothesis that the val66met BDNF polymorphism contributes toward variation in the human personality trait neuroticism, at least as indexed by the Eysenck Personality Questionnaire.

The serotonin transporter length polymorphism, neuroticism, and depression: a comprehensive assessment of association.

BACKGROUND: A promoter-based length polymorphism (5-HTTLPR) of the human serotonin gene (SLC6A4) has exhibited inconsistent association with emotionality phenotypes, such as major depression (MD) and the personality trait neuroticism (N). Several explanations have been posited to account for this discrepancy, including underpowered experimental design and variation in gender ratio, age, and ethnicity. METHODS: Here, we describe three independent tests of association between the 5-HTTLPR locus and both N and MD in samples selected for extremeness of N-score from two homogenous populations (n = 88,142, and 20,921). Calculations of statistical power indicated that at a 5% alpha level, these samples retain 100% power to detect a genetic effect accounting for just .5% of phenotypic variance. Effects of age were regressed out of the phenotypic measure, and gender was included as a covariate. RESULTS: No statistically significant effects of genotype could be identified on either N or MD phenotypes (in all cases, p > or = .26), independently of the genetic mode of action applied. CONCLUSIONS: Our data do not support the hypothesis that the 5-HTTLPR variant contributes significantly toward human emotionality as indexed by either the Eysenck Personality Questionnaire N scale or the DSM-IV for MD.