The Combined Dexamethasone/CRH Test (DEX/CRH Test) and Prediction of Acute Treatment Response in Major Depression

In this study the predictive value of the combined dexamethasone/CRH test (DEX/CRH test) for acute antidepressant response was investigated. In 114 depressed inpatients suffering from unipolar or bipolar depression (sample 1) the DEX/CRH test was performed at admission and shortly before discharge. During their stay in the hospital patients received different antidepressant treatment regimens. At admission, the rate of nonsuppression (basal cortisol levels >75.3 nmol/l) was 24.6% and was not related to the later therapeutic response. Moreover, 45 out of 114 (39.5%) patients showed an enhancement of HPA axis function at discharge in spite of clinical improvement. In a second sample, 40 depressed patients were treated either with reboxetine or mirtazapine for 5 weeks. The DEX/CRH test was performed before, after 1 week, and after 5 weeks of pharmacotherapy. Attenuation of HPA axis activity after 1 week was associated with a more pronounced alleviation of depressive symptoms after 5-week mirtazapine treatment, whereas downregulation of HPA system activity after 5 weeks was related to clinical response to reboxetine. However, early improvement of HPA axis dysregulation was not necessarily followed by a beneficial treatment outcome. Taken together, performance of a single DEX/CRH test does not predict the therapeutic response. The best predictor for response seems to be an early attenuation of HPA axis activity within 1 or 2 weeks. However, early improvement of HPA system dysfunction is not a sufficient condition for a favourable response. Since a substantial part of depressive patients display a persistence of HPA axis hyperactivity at discharge, downregulation of HPA system function is not a necessary condition for acute clinical improvement either. Our data underline the importance of HPA axis dysregulation for treatment outcome in major depression, although restoration of HPA system dysfunction seems to be neither a necessary nor a sufficient determinant for acute treatment response

Summary statistics in auditory perception

Sensory signals are transduced at high resolution, but their structure must be stored in a more compact format. Here we provide evidence that the auditory system summarizes the temporal details of sounds using time-averaged statistics. We measured discrimination of 'sound textures' that were characterized by particular statistical properties, as normally result from the superposition of many acoustic features in auditory scenes. When listeners discriminated examples of different textures, performance improved with excerpt duration. In contrast, when listeners discriminated different examples of the same texture, performance declined with duration, a paradoxical result given that the information available for discrimination grows with duration. These results indicate that once these sounds are of moderate length, the brain's representation is limited to time-averaged statistics, which, for different examples of the same texture, converge to the same values with increasing duration. Such statistical representations produce good categorical discrimination, but limit the ability to discern temporal detail.Howard Hughes Medical Institut

Chemical warfare between leafcutter ant symbionts and a co-evolved pathogen

Acromyrmex leafcutter ants form a mutually beneficial symbiosis with the fungus Leucoagaricus gongylophorus and with Pseudonocardia bacteria. Both are vertically transmitted and actively maintained by the ants. The fungus garden is manured with freshly cut leaves and provides the sole food for the ant larvae, while Pseudonocardia cultures are reared on the ant-cuticle and make antifungal metabolites to help protect the cultivar against disease. If left unchecked, specialized parasitic Escovopsis fungi can overrun the fungus-garden and lead to colony collapse. We report that Escovopsis upregulates the production of two specialized metabolites when it infects the cultivar. These compounds inhibit Pseudonocardia and one, shearinine D, also reduces worker behavioral defences and is ultimately lethal when it accumulates in ant tissues. Our results are consistent with an active evolutionary arms race between Pseudonocardia and Escovopsis, which modifies both bacterial and behavioral defences such that colony collapse is unavoidable once Escovopsis infections escalate

Association Analysis of the FTO Gene with Obesity in Children of Caucasian and African Ancestry Reveals a Common Tagging SNP

Recently an association was demonstrated between the single nucleotide polymorphism (SNP), rs9939609, within the FTO locus and obesity as a consequence of a genome wide association (GWA) study of type 2 diabetes in adults. We examined the effects of two perfect surrogates for this SNP plus 11 other SNPs at this locus with respect to our childhood obesity cohort, consisting of both Caucasians and African Americans (AA). Utilizing data from our ongoing GWA study in our cohort of 418 Caucasian obese children (BMI≥95th percentile), 2,270 Caucasian controls (BMI<95th percentile), 578 AA obese children and 1,424 AA controls, we investigated the association of the previously reported variation at the FTO locus with the childhood form of this disease in both ethnicities. The minor allele frequencies (MAF) of rs8050136 and rs3751812 (perfect surrogates for rs9939609 i.e. both r2 = 1) in the Caucasian cases were 0.448 and 0.443 respectively while they were 0.391 and 0.386 in Caucasian controls respectively, yielding for both an odds ratio (OR) of 1.27 (95% CI 1.08–1.47; P = 0.0022). Furthermore, the MAFs of rs8050136 and rs3751812 in the AA cases were 0.449 and 0.115 respectively while they were 0.436 and 0.090 in AA controls respectively, yielding an OR of 1.05 (95% CI 0.91–1.21; P = 0.49) and of 1.31 (95% CI 1.050–1.643; P = 0.017) respectively. Investigating all 13 SNPs present on the Illumina HumanHap550 BeadChip in this region of linkage disequilibrium, rs3751812 was the only SNP conferring significant risk in AA. We have therefore replicated and refined the association in an AA cohort and distilled a tag-SNP, rs3751812, which captures the ancestral origin of the actual mutation. As such, variants in the FTO gene confer a similar magnitude of risk of obesity to children as to their adult counterparts and appear to have a global impact

Selective Hyper-responsiveness of the Interferon System in Major Depressive Disorders and Depression Induced by Interferon Therapy

Though an important percentage of patients with chronic hepatitis C virus (HCV) undergoing interferon (IFN) therapy develop depressive symptoms, the role of the IFN system in the pathogenesis of depressive disorders is not well understood.50 patients with HCV infection were treated with standard combination therapy (pegylated IFN-α2a/ribavirin). IFN-induced gene expression was analyzed to identify genes which are differentially regulated in patients with or without IFN-induced depression. For validation, PBMC from 22 psychiatric patients with a severe depressive episode (SDE) and 11 controls were cultivated in vitro with pegylated IFN-α2a and gene expression was analyzed.IFN-induced depression in HCV patients was associated with selective upregulation of 15 genes, including 6 genes that were previously described to be relevant for major depressive disorders or neuronal development. In addition, increased endogenous IFN-production and selective hyper-responsiveness of these genes to IFN stimulation were observed in SDE patients.Our data suggest that selective hyper-responsiveness to exogenous (IFN therapy) or endogenous (depressive disorders) type I IFNs may lead to the development of depressive symptoms. These data could lead to the discovery of novel therapeutic approaches to treat IFN-induced and major depressive disorders

Modification of χc1(3872) and ψ(2S) production in pPb collisions at √sNN = 8.16 TeV

The LHCb Collaboration measures production of the exotic hadron χc1(3872) in proton-nucleus collisions for the first time. Comparison with the charmonium state ψ(2S) suggests that the exotic χc1(3872) experiences different dynamics in the nuclear medium than conventional hadrons, and comparison with data from proton-proton collisions indicates that the presence of the nucleus may modify χc1(3872) production rates. This is the first measurement of the nuclear modification factor of an exotic hadron

Measurements of the branching fraction ratio B(ϕ → μ+μ−) / B(ϕ → e+e−) with charm meson decays

Measurements of the branching fraction ratio B(ϕ → μ+μ−) / B(ϕ → e+e−) with Ds+→π+ϕ and D+→ π+ϕ decays, denoted Rϕπs and Rϕπd, are presented. The analysis is performed using a dataset corresponding to an integrated luminosity of 5.4 fb−1 of pp collision data collected with the LHCb experiment. The branching fractions are normalised with respect to the B+ → K+J/ψ(→ e+e−) and B+ → K+J/ψ(→ μ+μ−) decay modes. The combination of the results yieldsRϕπ=1.022±0.012stat±0.048syst. The result is compatible with previous measurements of the ϕ → ℓ+ℓ− branching fractions and predictions based on the Standard Model

Amplitude analysis of the B0→K*0μ+μ− decay

An amplitude analysis of the B 0 → K * 0 μ + μ − decay is presented using a dataset corresponding to an integrated luminosity of 4.7     fb − 1 of p p collision data collected with the LHCb experiment. For the first time, the coefficients associated to short-distance physics effects, sensitive to processes beyond the standard model, are extracted directly from the data through a q 2 -unbinned amplitude analysis, where q 2 is the μ + μ − invariant mass squared. Long-distance contributions, which originate from nonfactorizable QCD processes, are systematically investigated, and the most accurate assessment to date of their impact on the physical observables is obtained. The pattern of measured corrections to the short-distance couplings is found to be consistent with previous analyses of b - to s -quark transitions, with the largest discrepancy from the standard model predictions found to be at the level of 1.8 standard deviations. The global significance of the observed differences in the decay is 1.4 standard deviations

Enhanced production of Λb0 baryons in high-multiplicity pp collisions at √s = 13 TeV

The production rate of Λ 0 b baryons relative to B 0 mesons in p p collisions at a center-of-mass energy √ s = 13     TeV is measured by the LHCb experiment. The ratio of Λ 0 b to B 0 production cross sections shows a significant dependence on both the transverse momentum and the measured charged-particle multiplicity. At low multiplicity, the ratio measured at LHCb is consistent with the value measured in e + e − collisions, and increases by a factor of ∼ 2 with increasing multiplicity. At relatively low transverse momentum, the ratio of Λ 0 b to B 0 cross sections is higher than what is measured in e + e − collisions, but converges with the e + e − ratio as the momentum increases. These results imply that the evolution of heavy b quarks into final-state hadrons is influenced by the density of the hadronic environment produced in the collision. Comparisons with several models and implications for the mechanisms enforcing quark confinement are discussed