Weak-signal conversion from 1550nm to 532nm with 84% efficiency

We report on the experimental frequency conversion of a dim, coherent continuous-wave light field from 1550nm to 532nm with an external photon-number conversion efficiency of (84.4 +/- 1.5)%. We used sum-frequency generation, which was realized in a standing-wave cavity built around a periodically poled type I potassium titanyl phosphate (PPKTP) crystal, pumped by an intense field at 810 nm. Our result is in full agreement with a numerical model. For optimized cavity coupler reflectivities it predicts a conversion efficiency of up to 93% using the same PPKTP crystal

A novel strategy for clustering major depression individuals using whole-genome sequencing variant data

Major depressive disorder (MDD) is highly prevalent, resulting in an exceedingly high disease burden. The identification of generic risk factors could lead to advance prevention and therapeutics. Current approaches examine genotyping data to identify specific variations between cases and controls. Compared to genotyping, whole-genome sequencing (WGS) allows for the detection of private mutations. In this proof-of-concept study, we establish a conceptually novel computational approach that clusters subjects based on the entirety of their WGS. Those clusters predicted MDD diagnosis. This strategy yielded encouraging results, showing that depressed Mexican-American participants were grouped closer; in contrast ethnically-matched controls grouped away from MDD patients. This implies that within the same ancestry, the WGS data of an individual can be used to check whether this individual is within or closer to MDD subjects or to controls. We propose a novel strategy to apply WGS data to clinical medicine by facilitating diagnosis through genetic clustering. Further studies utilising our method should examine larger WGS datasets on other ethnical groups.Chenglong Yu, Bernhard T. Baune, Julio Licinio and Ma-Li Won

Unconditional entanglement interface for quantum networks

Entanglement drives nearly all proposed quantum information technologies. The suppression of the uncertainty in joint quadrature measurements below the level of vacuum fluctuations is a signature of non-classical correlations. Entangling frequency modes of optical fields has attracted increased attention in recent years, as a quantum network would rely on interfacing light at telecommunication wavelengths with matter-based quantum memories that are addressable at visible wavelengths. By up-converting part of a 1550 nm squeezed vacuum state to 532 nm, we demonstrate the generation and complete characterization of strong continuous-variable entanglement between widely separated frequencies. Non-classical correlations were observed in joint quadrature measurements of the 1550 nm and 532 nm fields, showing a maximum noise suppression 5.5 dB below vacuum. A spectrum was measured to demonstrate over 3 dB noise suppression up to 20 MHzmeasurement frequency. Our versatile technique combines strong non-classical correlations, large bandwidth and, in principle, the ability to entangle the telecommunication wavelength of 1550 nm with any optical wavelength, making this approach highly relevant to emerging proposals for quantum communication and computing

Effects of centrally administered etanercept on behaviour, histology and TNF-α expression in mice following a peripheral immune challenge

Background: Peripheral cytokines affect central nervous system (CNS) function, triggering anxiety and cognitive decline. Although peripheral blockade of tumor necrosis factor (TNF-α) by etanercept, has been effective in alleviating rheumatoid arthritis, it is yet unknown whether central blockade of TNF-α is beneficial for immune-challenged CNS function. This study investigated effects of central etanercept administration post-peripheral immune challenge, on behaviour and histology. Methods: 12-week-old C57BL/6 mice (n=40) were challenged with either LPS or saline, administered peripherally 24hr before being treated with etanercept or artificial CSF (aCSF), via intracerebroventricular injection. Mice underwent behavioural analyses for locomotion (open field test: OFT), memory (Y maze) and anxiety (elevated zero maze: EZM) 24hr post etanercept/aCSF treatment. Brain tissue was then collected to estimate number of hippocampal microglia and expression of Tnfa. Results: Acute systemic challenge with LPS decreased weight in mice at 24hr, and impaired locomotor activity. LPS significantly increased anxiety-like behaviour (2-way ANOVA: Interaction: P=0.096; Saline/LPS challenge: P=0.0006, aCSF/etanercept treatment: P=0.0008), which was reversed by etanercept and significantly reduced cognition in the Y Maze (Interaction: P=0.037, Saline/LPS challenge: P=0.31, aCSF/etanercept treatment: P=0.80), which was not reversed by etanercept. LPS challenge also increased Tnfa expression in the hippocampus (Interaction: F(1,13)=28.04, P=0.0001, Saline/LPS challenge: P=0.0003, aCSF/etanercept treatment: P=0.021) and etanercept treatment was effective in reducing this Tnfa expression (P=0.001). Etanercept also significantly reduced microglial numbers within the hippocampus, which were increased following LPS administration (2-way ANOVA: Interaction: P= 0.0041; Saline/LPS challenge: P<0.0001, etanercept/aCSF: P=0.08,). Conclusion: A single dose of etanercept was found to be effective in significantly decreasing anxiety, Tnfa expression and microglia numbers 48hr post-peripheral immune challenge. The present study suggests that there is effective cross-talk between peripheral and central immune systems. Additionally behavioural and biological changes caused by LPS challenge which may be mediated by TNF-α related central inflammation, were reversed by etanercept treatment

Epigenetic alterations following early postnatal stress: a review on novel aetiological mechanisms of common psychiatric disorders

Stressor exposure during early life has the potential to increase an individual’s susceptibility to a number of neuropsychiatric conditions such as mood and anxiety disorders and schizophrenia in adulthood. This occurs in part due to the dysfunctional stress axis that persists following early adversity impairing stress responsivity across life. The mechanisms underlying the prolonged nature of this vulnerability remain to be established. Alterations in the epigenetic signature of genes involved in stress responsivity may represent one of the neurobiological mechanisms. The overall aim of this review is to provide current evidence demonstrating changes in the epigenetic signature of candidate gene(s) in response to early environmental adversity. More specifically, this review analyses the epigenetic signatures of postnatal adversity such as childhood abuse or maltreatment and later-life psychopathology in human and animal models of early life stress. The results of this review shows that focus to date has been on genes involved in the regulation of hypothalamic-pituitary-adrenal (HPA) axis and its correlation to subsequent neurobiology, for example, the role of glucocorticoid receptor gene. However, epigenetic changes in other candidate genes such as brain-derived neurotrophic factor (BDNF) and serotonin transporter are also implicated in early life stress (ELS) and susceptibility to adult psychiatric disorders. DNA methylation is the predominantly studied epigenetic mark followed by histone modifications specifically acetylation and methylation. Further, these epigenetic changes are cell/tissue-specific in regulating expression of genes, providing potential biomarkers for understanding the trajectory of early stress-induced susceptibility to adult psychiatric disorders

Anti-inflammatory treatment of depression: study protocol for a randomised controlled trial of vortioxetine augmented with celecoxib or placebo

BACKGROUND:In patients with major depressive disorder (MDD), antidepressant response and remission rates are low, highlighting the need for new treatment approaches. Recently, the abundant literature linking inflammatory processes and depressive symptoms have led to the hypothesis that selecting treatment for MDD based on the patient's inflammatory status could be a promising strategy to improve outcomes in patients suffering from MDD. The aim of the randomised control trial we propose is to investigate the antidepressant efficacy of the combined treatment of MDD with antidepressant medication plus anti-inflammatory medication in individuals with raised inflammation levels. For the first time, this study will prospectively test the efficacy of an antidepressant plus anti-inflammatory augmentation based on baseline inflammatory maker levels in MDD using a randomised controlled trial design. METHODS:This study proposes to measure blood C-reactive protein (CRP) levels before the initiation of treatment in 200 participants with MDD. Study participants are then assigned into one of two study strata: either into the 'Depression with inflammation' stratum (CRP levels > 3 mg/L); or into the 'Depression without inflammation' stratum (CRP levels ≤ 3 mg/L). Within each of the two study strata, participants randomly receive either antidepressant medication alone (vortioxetine) plus anti-inflammatory medication (celecoxib) or vortioxetine plus placebo for six weeks. At the end of the treatment period, participants have the opportunity to continue vortioxetine alone for a six-month post-trial period. Clinical outcomes are measured at baseline, fortnightly during the treatment period and at the three-month and six-month post-trial visits. The primary outcome is change in MADRS score, with a primary endpoint of a score reduction by 50% from baseline to six weeks (end of augmentation treatment with celecoxib). Secondary clinical outcomes are changes in the cognitive dimensions of depression (cognitive function, emotion processing and social cognition). Biological outcome measures (levels of CRP and other inflammatory markers) are measured at baseline, after six weeks of treatment and at the six-month post-trial visit. DISCUSSION:The current study will generate novel evidence for biomarker-based personalised antidepressant treatment selection based on patient inflammatory status before treatment. TRIAL REGISTRATION:Australian New Zealand Clinical Trials Registry (ANZCTR), ACTRN12617000527369p . Registered on 11 April 2017.Célia Fourrier, Emma Sampson, Natalie T. Mills and Bernhard T. Baun

Anti-inflammatory effects of antidepressant and atypical antipsychotic medication for the treatment of major depression and comorbid arthritis: a case report

Extent: 4p.Introduction: This case report describes the effects of psychotropic treatment, quetiapine in particular, on systemic inflammation, pain, general functioning and major depression in the treatment of a woman with arthritis. Case presentation: A 49-year-old Caucasian Australian woman with arthritis, pain and depression was treated with a course of escitalopram, mirtazapine and quetiapine. Pain levels, general functioning and degree of depressive symptoms were evaluated with a visual analogue scale. Systemic inflammation had been assessed by C-reactive protein serum levels since 2003. C-reactive protein levels, physical pain, symptoms of arthritis and depression decreased significantly during the past 12 months of treatment with quetiapine, while treatment with selective serotonin reuptake inhibitors and mirtazapine remained the same. Conclusions: We suggest that the treatment particularly with quetiapine may have anti-inflammatory effects in arthritis and comorbid major depression, which eventually led to a remission of pain and depression and to normal general function.Bernhard T Baune, Harris Eyr