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Contains fulltext : 160014.pdf (Publisher’s version ) (Open Access), Background: Major depressive disorder (MDD) exhibits numerous clinical and molecular features that are consistent with putative epigenetic misregulation. Despite growing interest in epigenetic studies of psychiatric diseases, the methodologies guiding such studies have not been well defined. Methods: We performed DNA modification analysis in white blood cells from monozygotic twins discordant for MDD, in brain prefrontal cortex, and germline (sperm) samples from affected individuals and control subjects (total N = 304) using 8.1K CpG island microarrays and fine mapping. In addition to the traditional locus-by-locus comparisons, we explored the potential of new analytical approaches in epigenomic studies. Results: In the microarray experiment, we detected a number of nominally significant DNA modification differences in MDD and validated selected targets using bisulfite pyrosequencing. Some MDD epigenetic changes, however, overlapped across brain, blood, and sperm more often than expected by chance. We also demonstrated that stratification for disease severity and age may increase the statistical power of epimutation detection. Finally, a series of new analytical approaches, such as DNA modification networks and machine-learning algorithms using binary and quantitative depression phenotypes, provided additional insights on the epigenetic contributions to MDD. Conclusions: Mapping epigenetic differences in MDD (and other psychiatric diseases) is a complex task. However, combining traditional and innovative analytical strategies may lead to identification of disease-specific etiopathogenic epimutations.

Objective: To examine the predictive role of insomnia andsleep duration on the 2-year course of depressive andanxiety disorders. Method: This study is a secondary data analysis based ondata from the baseline (2004-2007) and 2-year assessmentof the Netherlands Study of Depression and Anxiety.Participants were 1,069 individuals with DSM-IV-baseddepressive and/or anxiety disorders at baseline. Sleepmeasures included insomnia (Women's Health InitiativeInsomnia Rating Scale score ≥ 9) and sleep duration(categorized as short [≤ 6 hours], normal [7-9 hours], orlong [≥ 10 hours]). Outcome measures were persistence of DSM-IV depressive and anxiety disorders (currentdiagnosis at 2-year follow-up), time to remission, andclinical course trajectory of symptoms (early sustainedremission, late remission/recurrence, and chroniccourse). Logistic regression analyses were adjusted forsociodemographic characteristics and chronic medicaldisorders, psychotropic medications, and severity ofdepressive and anxiety symptoms. Results: The effect of insomnia on persistence of depressiveand/or anxiety disorders (OR = 1.50; 95% CI, 1.16-1.94)was explained by severity of baseline depressive/anxietysymptoms (adjusted OR with severity = 1.04; 95% CI,0.79-1.37). Long sleep duration was independentlyassociated with persistence of depression/anxiety evenafter adjusting for severity of psychiatric symptoms(OR = 2.52; 95% CI, 1.27-4.99). For short sleep duration, theindependent association with persistence of combineddepression/anxiety showed a trend toward significance(OR = 1.32; 95% CI, 0.98-1.78), and a significant associationfor the persistence of depressive disorders (OR = 1.49; 95%CI, 1.11-2.00). Both short and long sleep duration wereindependently associated with a chronic course trajectory(short sleep: OR = 1.50; 95% CI, 1.04-2.16; long sleep:OR = 2.91, 95% CI, 1.22-6.93). Discussion: Both short and long sleep duration-but not insomni

Humans sleep approximately a third of their lifetime. The observation that individuals with either long or short sleep duration show associations with metabolic syndrome and psychiatric disorders suggests that the length of sleep is adaptive. Although sleep duration can be influenced by photoperiod (season) and phase of entrainment (chronotype), human familial sleep disorders indicate that there is a strong genetic modulation of sleep. Therefore, we conducted high-density genome-wide association studies for sleep duration in seven European populations (N=4251). We identified an intronic variant (rs11046205; P=3.99 x 10(-8)) in the ABCC9 gene that explains approximate to 5% of the variation in sleep duration. An influence of season and chronotype on sleep duration was solely observed in the replication sample (N=5949). Meta-analysis of the associations found in a subgroup of the replication sample, chosen for season of entry and chronotype, together with the discovery results showed genome-wide significance. RNA interference knockdown experiments of the conserved ABCC9 homologue in Drosophila neurons renders flies sleepless during the first 3 h of the night. ABCC9 encodes an ATP-sensitive potassium channel subunit (SUR2), serving as a sensor of intracellular energy metabolism. Molecular Psychiatry (2013) 18, 122-132; doi:10.1038/mp.2011.142; published online 22 November 2011

Background: A multidisciplinary team of 20 researchers and research users from six countries – Canada, Jamaica, Barbados, Kenya, Uganda and South Africa – are collaborating on a 5-year (2007–12) program of research and capacity building project. This program of research situates nurses as leaders in building capacity and promotes collaborative action with other health professionals and decision-makers to improve health systems for human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) nursing care. One of the projects within this program of research focused on the influence of workplace policies on nursing care for individuals and families living with HIV. Nurses are at the forefront of HIV prevention and AIDS care in these countries but have limited involvement in related policy decisions and development. In this paper, we present findings related to the barriers and facilitators for nurses' engagement in policymaking. Methods: A participatory action research design guided the program of research. Purposive sampling was used to recruit 51 nurses (unit managers, clinic and healthcare managers, and senior nurse officers) for interviews. Findings: Participants expressed the urgent need to develop policies related to AIDS care. The need to raise awareness and to ‘protect’ not only the workers but also the patients were critical reason to develop policies. Nurses in all of the participating countries commented on their lack of involvement in policy development. Lack of communication from the top down and lack of information sharing were mentioned as barriers to participation in policy development. Resources were often not available to implement the policy requirement. Strong support from the management team is necessary to facilitate nurses involvement in policy development. Conclusions: The findings of this study clearly express the need for nurses and all other stakeholders to mobilize nurses' involvement in policy development. Long-term

Age-related changes in DNA methylation have been implicated in cellular senescence and longevity, yet the causes and functional consequences of these variants remain unclear. To elucidate the role of age-related epigenetic changes in healthy ageing and potential longevity, we tested for association between whole-blood DNA methylation patterns in 172 female twins aged 32 to 80 with age and age-related phenotypes. Twin-based DNA methylation levels at 26,690 CpG-sites showed evidence for mean genome-wide heritability of 18%, which was supported by the identification of 1,537 CpG-sites with methylation QTLs in cis at FDR 5%. We performed genome-wide analyses to discover differentially methylated regions (DMRs) for sixteen age-related phenotypes (ap-DMRs) and chronological age (a-DMRs). Epigenome-wide association scans (EWAS) identified age-related phenotype DMRs (ap-DMRs) associated with LDL (STAT5A), lung function (WT1), and maternal longevity (ARL4A, TBX20). In contrast, EWAS for chronological age identified hundreds of predominantly hyper-methylated age DMRs (490 a-DMRs at FDR 5%), of which only one (TBX20) was also associated with an age-related phenotype. Therefore, the majority of age-related changes in DNA methylation are not associated with phenotypic measures of healthy ageing in later life. We replicated a large proportion of a-DMRs in a sample of 44 younger adult MZ twins aged 20 to 61, suggesting that a-DMRs may initiate at an earlier age. We next explored potential genetic and environmental mechanisms underlying a-DMRs and ap-DMRs. Genome-wide overlap across cis-meQTLs, genotype-phenotype associations, and EWAS ap-DMRs identified CpG-sites that had cis-meQTLs with evidence for genotype-phenotype association, where the CpG-site was also an ap-DMR for the same phenotype. Monozygotic twin methylation difference analyses identified one potential environmentally-mediated ap-DMR associated with total cholesterol and LDL (CSMD1). Our results suggest that in a smal

Studies of the major psychoses, schizophrenia (SZ) and bipolar disorder (BD), have traditionally focused on genetic and environmental risk factors, although more recent work has highlighted an additional role for epigenetic processes in mediating susceptibility. Since monozygotic (MZ) twins share a common DNA sequence, their study represents an ideal design for investigating the contribution of epigenetic factors to disease etiology. We performed a genome-wide analysis of DNA methylation on peripheral blood DNA samples obtained from a unique sample of MZ twin pairs discordant for major psychosis. Numerous loci demonstrated disease-associated DNA methylation differences between twins discordant for SZ and BD individually, and together as a combined major psychosis group. Pathway analysis of our top loci highlighted a significant enrichment of epigenetic changes in biological networks and pathways directly relevant to psychiatric disorder and neurodevelopment. The top psychosis-associated, differentially methylated region, significantly hypomethylated in affected twins, was located in the promoter of ST6GALNAC1 overlapping a previously reported rare genomic duplication observed in SZ. The mean DNA methylation difference at this locus was 6%, but there was considerable heterogeneity between families, with some twin pairs showing a 20% difference in methylation. We subsequently assessed this region in an independent sample of postmortem brain tissue from affected individuals and controls, finding marked hypomethylation (>25%) in a subset of psychosis patients. Overall, our data provide further evidence to support a role for DNA methylation differences in mediating phenotypic differences between MZ twins and in the etiology of both SZ and BD.

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We say that a space X has the separation property provided that if A and B are subsets of X with A countable and B first category, then there is a homeomorphism f: X → X such that f(A) ∩ B = Ø. We prove that a Borel space with this property is Polish. Our main result is that if the homeomorphisms needed in the separation property for the space X come from the homeomorphisms given by an action of an analytic group, then X is Polish. Several examples are also presented. © 2009 American Mathematical Society.

We show that for any sufficiently homogeneous metrizable compactum X there is a Polish group G acting continuously on the space of rational numbers Q such that X is its unique G-compactification. This allows us to answer Problem 995 in the 'Open Problems in Topology II' book in the negative: there is a one-dimensional Polish group G acting transitively on Q for which the Hilbert cube is its unique G-completion. © 2008 Springer-Verlag.

Contains fulltext : 70196.pdf (publisher's version ) (Closed access), Season of birth (SOB) has been associated with attention deficit hyperactivity disorder (ADHD) in two existing studies. One further study reported an interaction between SOB and genotypes of the dopamine D4 receptor (DRD4) gene. It is important that these findings are further investigated to confirm or refute the findings. In this study, we investigated the SOB association with ADHD in four independent samples collected for molecular genetic studies of ADHD and found a small but significant increase in summer births compared to a large population control dataset. We also observed a significant association with the 7-repeat allele of the DRD4 gene variable number tandem repeat polymorphism in exon three with probands born in the winter season, with no significant differential transmission of this allele between summer and winter seasons. Preferential transmission of the 2-repeat allele to ADHD probands occurred in those who were born during the summer season, but did not surpass significance for association, even though the difference in transmission between the two seasons was nominally significant. However, following adjustment for multiple testing of alleles none of the SOB effects remained significant. We conclude that the DRD4 7-repeat allele is associated with ADHD but there is no association or interaction with SOB for increased risk for ADHD. Our findings suggest that we can refute a possible effect of SOB for ADHD.

We prove that for every homogeneous and strongly locally homogeneous Polish space X there is a Polish group admitting a transitive action on X. We also construct an example of a homogeneous Polish space which is not a coset space and on which no separable metrizable topological group acts transitively. © 2008 The Hebrew University of Jerusalem.