Risk factor profiles for depression following childbirth or a chronic disease diagnosis:case-control study

BACKGROUND: Progress towards understanding the aetiology of major depression is compromised by its clinical heterogeneity. The variety of contexts underlying the development of a major depressive episode may contribute to such heterogeneity. AIMS: To compare risk factor profiles for three subgroups of major depression according to episode context. METHOD: Using self-report questionnaires and administrative records from the UK Biobank, we characterised three contextual subgroups of major depression: postpartum depression (3581 cases), depression following diagnosis of a chronic disease (409 cases) and a more typical (named heterogeneous) major depression phenotype excluding the two other contexts (34 699 cases). Controls with the same exposure were also defined. We tested each subgroup for association with the polygenic risk scores (PRS) for major depression and with other risk factors previously associated with major depression (bipolar disorder PRS, neuroticism, reported trauma in childhood and adulthood, socioeconomic status, family history of depression, education). RESULTS: Major depression PRS was associated with all subgroups, but postpartum depression cases had higher PRS than heterogeneous major depression cases (OR = 1.06, 95% CI 1.02–1.10). Relative to heterogeneous depression, postpartum depression was more weakly associated with adulthood trauma and neuroticism. Depression following diagnosis of a chronic disease had weaker association with neuroticism and reported trauma in adulthood and childhood relative to heterogeneous depression. CONCLUSIONS: The observed differences in risk factor profiles according to the context of a major depressive episode help provide insight into the heterogeneity of depression. Future studies dissecting such heterogeneity could help reveal more refined aetiological insights

Relative Age Effects on Attention-Deficit/Hyperactivity Disorder Symptoms and Educational Achievement:A Longitudinal UK Cohort Study

ObjectiveBeing among the youngest in a school class increases the risk for worse educational outcomes and attention-deficit/hyperactivity disorder (ADHD) symptoms, but questions remain about the nature and persistence of such effects. We investigated this “relative age effect” on educational achievement at age 15 to 16 years and on ADHD symptoms from age 7 to age 21 years. Furthermore, we examined whether being young-in-class is linked to a greater reduction in ADHD symptoms from childhood to adulthood and a lower genetic propensity to ADHD.MethodWe identified 3,928 young-in-class and 4,580 old-in-class participants from the Twins’ Early Development Study. Educational achievement was measured with mathematics and English examination grades at age 15 to 16 years, and ADHD symptoms were measured using 2 different scales and different raters, from age 7 to 21 years, with effects tested using regression.ResultsA relative age effect emerged for English but not mathematics examination grades, and for the majority of parent and teacher ratings on ADHD symptoms, most consistently in middle childhood. Being young-in-class was associated with a greater reduction in parent-rated ADHD symptoms from childhood to adulthood when measured with a brief scale, but the comparable result from a longer scale was non-significant (after multiple testing correction). No interaction emerged between relative age and ADHD polygenic scores.ConclusionOur results emphasise the need to improve support for the children who start school younger than most, and to ensure that developmental comparisons take children’s precise age into account. Future research would benefit from in-depth analyses of individual trajectories and their variability among the young-in-class children.</div

Rates and Characteristics of Intermediate Mass Ratio Inspirals Detectable by Advanced LIGO

Gravitational waves (GWs) from the inspiral of a neutron star (NS) or stellar-mass black hole (BH) into an intermediate-mass black hole (IMBH) with mass between ~50 and ~350 solar masses may be detectable by the planned advanced generation of ground-based GW interferometers. Such intermediate mass ratio inspirals (IMRIs) are most likely to be found in globular clusters. We analyze four possible IMRI formation mechanisms: (1) hardening of an NS-IMBH or BH-IMBH binary via three-body interactions, (2) hardening via Kozai resonance in a hierarchical triple system, (3) direct capture, and (4) inspiral of a compact object from a tidally captured main-sequence star; we also discuss tidal effects when the inspiraling object is an NS. For each mechanism we predict the typical eccentricities of the resulting IMRIs. We find that IMRIs will have largely circularized by the time they enter the sensitivity band of ground-based detectors. Hardening of a binary via three-body interactions, which is likely to be the dominant mechanism for IMRI formation, yields eccentricities under 10^-4 when the GW frequency reaches 10 Hz. Even among IMRIs formed via direct captures, which can have the highest eccentricities, around 90% will circularize to eccentricities under 0.1 before the GW frequency reaches 10 Hz. We estimate the rate of IMRI coalescences in globular clusters and the sensitivity of a network of three Advanced LIGO detectors to the resulting GWs. We show that this detector network may see up to tens of IMRIs per year, although rates of one to a few per year may be more plausible. We also estimate the loss in signal-to-noise ratio that will result from using circular IMRI templates for data analysis and find that, for the eccentricities we expect, this loss is negligible.Comment: Accepted for publication in ApJ; revised version reflects changes made to the article during the acceptance proces

DNA methylation of FKBP5 and response to exposure-based psychological therapy

Differential DNA methylation of the HPA-axis related gene FKBP5 has recently been shown to be associated with varying response to environmental influences, and may play a role in how well people respond to psychological treatments. Participants (n=111) received exposure-based CBT for agoraphobia with or without panic disorder, or specific phobias. Percentage DNA methylation levels were measured for the promoter region and intron 7 of FKBP5. The association between percentage reduction in clinical severity and change in DNA methylation was tested using linear mixed models. The effect of genotype (rs1360780) was tested by the inclusion of an interaction term. The association between change in DNA methylation and FKBP5 expression was examined. Change in percentage DNA methylation at one CpG site of intron 7 was associated with percentage reduction in severity (β=-4.26, p=3.90x10-4), where a decrease in DNA methylation was associated with greater response to therapy. An interaction was detected between rs1360780 and changes in DNA methylation in the promoter region of FKBP5 on treatment outcome (p=0.045), but did not survive correction for multiple testing. Changes in DNA methylation were not associated with FKBP5 expression. Decreasing DNA methylation at one CpG site of intron 7 of FKBP5 was strongly associated with decreasing anxiety severity following exposure-based CBT. In addition, there was suggestive evidence that allele-specific methylation at the promoter region may also be associated with treatment response. The results of this study add to the growing literature demonstrating the role of biological processes such as DNA methylation in response to environmental influences

Characteristic QSO Accretion Disk Temperatures from Spectroscopic Continuum Variability

Using Sloan Digital Sky Survey (SDSS) quasar spectra taken at multiple epochs, we find that the composite flux density differences in the rest frame wavelength range 1300-6000 AA can be fit by a standard thermal accretion disk model where the accretion rate has changed from one epoch to the next (without considering additional continuum emission components). The fit to the composite residual has two free parameters: a normalizing constant and the average characteristic temperature $\bar{T}^*$. In turn the characteristic temperature is dependent on the ratio of the mass accretion rate to the square of the black hole mass. We therefore conclude that most of the UV/optical variability may be due to processes involving the disk, and thus that a significant fraction of the UV/optical spectrum may come directly from the disk.Comment: 31 pages, 8 figure

Genome-wide association study identifies 30 Loci Associated with Bipolar Disorder

Bipolar disorder is a highly heritable psychiatric disorder. We performed a genome-wide association study including 20,352 cases and 31,358 controls of European descent, with follow-up analysis of 822 variants with P\u3c1×10−4 in an additional 9,412 cases and 137,760 controls. Eight of the 19 variants that were genome-wide significant (GWS, p \u3c 5×10−8) in the discovery GWAS were not GWS in the combined analysis, consistent with small effect sizes and limited power but also with genetic heterogeneity. In the combined analysis 30 loci were GWS including 20 novel loci. The significant loci contain genes encoding ion channels, neurotransmitter transporters and synaptic components. Pathway analysis revealed nine significantly enriched gene-sets including regulation of insulin secretion and endocannabinoid signaling. BDI is strongly genetically correlated with schizophrenia, driven by psychosis, whereas BDII is more strongly correlated with major depressive disorder. These findings address key clinical questions and provide potential new biological mechanisms for BD

Sum-over-histories origin of the composition laws of relativistic quantum mechanics and quantum cosmology

The scope of the paper has been broadened to include a more complete discussion of the following topics: The derivation of composition laws in quantum cosmology. The connection between the existence of a composition law in the sum over histories approach to relativistic quantum mechanics and quantum cosmology, and the existence of a canonical formulation.Comment: 36 page

Electroweak Symmetry Breaking in the DSSM

We study the theoretical and phenomenological consequences of modifying the Kahler potential of the MSSM two Higgs doublet sector. Such modifications naturally arise when the Higgs sector mixes with a quasi-hidden conformal sector, as in some F-theory GUT models. In the Delta-deformed Supersymmetric Standard Model (DSSM), the Higgs fields are operators with non-trivial scaling dimension 1 < Delta < 2. The Kahler metric is singular at the origin of field space due to the presence of quasi-hidden sector states which get their mass from the Higgs vevs. The presence of these extra states leads to the fact that even as Delta approaches 1, the DSSM does not reduce to the MSSM. In particular, the Higgs can naturally be heavier than the W- and Z-bosons. Perturbative gauge coupling unification, a large top quark Yukawa, and consistency with precision electroweak can all be maintained for Delta close to unity. Moreover, such values of Delta can naturally be obtained in string-motivated constructions. The quasi-hidden sector generically contains states charged under SU(5)_GUT as well as gauge singlets, leading to a rich, albeit model-dependent, collider phenomenology.Comment: v3: 40 pages, 3 figures, references added, typos correcte