Biological markers for anxiety disorders, OCD and PTSD: A consensus statement. Part II: Neurochemistry, neurophysiology and neurocognition.

OBJECTIVE: Biomarkers are defined as anatomical, biochemical or physiological traits that are specific to certain disorders or syndromes. The objective of this paper is to summarise the current knowledge of biomarkers for anxiety disorders, obsessive-compulsive disorder (OCD) and posttraumatic stress disorder (PTSD). METHODS: Findings in biomarker research were reviewed by a task force of international experts in the field, consisting of members of the World Federation of Societies for Biological Psychiatry Task Force on Biological Markers and of the European College of Neuropsychopharmacology Anxiety Disorders Research Network. RESULTS: The present article (Part II) summarises findings on potential biomarkers in neurochemistry (neurotransmitters such as serotonin, norepinephrine, dopamine or GABA, neuropeptides such as cholecystokinin, neurokinins, atrial natriuretic peptide, or oxytocin, the HPA axis, neurotrophic factors such as NGF and BDNF, immunology and CO2 hypersensitivity), neurophysiology (EEG, heart rate variability) and neurocognition. The accompanying paper (Part I) focuses on neuroimaging and genetics. CONCLUSIONS: Although at present, none of the putative biomarkers is sufficient and specific as a diagnostic tool, an abundance of high quality research has accumulated that should improve our understanding of the neurobiological causes of anxiety disorders, OCD and PTSD.The present work was supported by the Anxiety Disorders Research Network (ADRN) within the European College of Neuropsychopharmacology Network Initiative (ECNP-NI). Katherina Domschke’s work was supported by the German Research Foundation (DFG), Collaborative Research Centre “Fear, Anxiety, Anxiety Disorders” SFB-TRR-58, project C02.This is the author accepted manuscript. The final version is available from Taylor & Francis via http://dx.doi.org/10.1080/15622975.2016.119086

A multi-country test of brief reappraisal interventions on emotions during the COVID-19 pandemic.

The COVID-19 pandemic has increased negative emotions and decreased positive emotions globally. Left unchecked, these emotional changes might have a wide array of adverse impacts. To reduce negative emotions and increase positive emotions, we tested the effectiveness of reappraisal, an emotion-regulation strategy that modifies how one thinks about a situation. Participants from 87 countries and regions (n = 21,644) were randomly assigned to one of two brief reappraisal interventions (reconstrual or repurposing) or one of two control conditions (active or passive). Results revealed that both reappraisal interventions (vesus both control conditions) consistently reduced negative emotions and increased positive emotions across different measures. Reconstrual and repurposing interventions had similar effects. Importantly, planned exploratory analyses indicated that reappraisal interventions did not reduce intentions to practice preventive health behaviours. The findings demonstrate the viability of creating scalable, low-cost interventions for use around the world

An Oldie but Goodie: Lithium in the Treatment of Bipolar Disorder through Neuroprotective and Neurotrophic Mechanisms

Lithium has been used for the treatment of bipolar disorder (BD) for the last sixty or more years, and recent studies with more reliable designs and updated guidelines have recommended lithium to be the treatment of choice for acute manic, mixed and depressive episodes of BD, along with long-term prophylaxis. Lithium’s specific mechanism of action in mood regulation is progressively being clarified, such as the direct inhibition on glycogen synthase kinase 3β, and its various effects on neurotrophic factors, neurotransmitters, oxidative metabolism, apoptosis, second messenger systems, and biological systems are also being revealed. Furthermore, lithium has been proposed to exert its treatment effects through mechanisms associated with neuronal plasticity. In this review, we have overviewed the clinical aspects of lithium use for BD, and have focused on the neuroprotective and neurotrophic effects of lithium

Neuroinflammation-Associated Alterations of the Brain as Potential Neural Biomarkers in Anxiety Disorders

Stress-induced changes in the immune system, which lead to neuroinflammation and consequent brain alterations, have been suggested as possible neurobiological substrates of anxiety disorders, with previous literature predominantly focusing on panic disorder, agoraphobia, and generalized anxiety disorder, among the anxiety disorders. Anxiety disorders have frequently been associated with chronic stress, with chronically stressful situations being reported to precipitate the onset of anxiety disorders. Also, chronic stress has been reported to lead to hypothalamic–pituitary–adrenal axis and autonomic nervous system disruption, which may in turn induce systemic proinflammatory conditions. Preliminary evidence suggests anxiety disorders are also associated with increased inflammation. Systemic inflammation can access the brain, and enhance pro-inflammatory cytokine levels that have been shown to precipitate direct and indirect neurotoxic effects. Prefrontal and limbic structures are widely reported to be influenced by neuroinflammatory conditions. In concordance with these findings, various imaging studies on panic disorder, agoraphobia, and generalized anxiety disorder have reported alterations in structure, function, and connectivity of prefrontal and limbic structures. Further research is needed on the use of inflammatory markers and brain imaging in the early diagnosis of anxiety disorders, along with the possible efficacy of anti-inflammatory interventions on the prevention and treatment of anxiety disorders

Optimal Implementation Parameters of a Nonlinear Electrical Impedance Tomography Method Using the Complete Electrode Model

This study discusses a nonlinear electrical impedance tomography (EIT) technique under different analysis conditions to propose its optimal implementation parameters. The forward problem for calculating electric potential is defined by the complete electrode model. The inverse problem for reconstructing the target electrical conductivity profile is presented based on a partial-differential-equation-constrained optimization approach. The electrical conductivity profile is iteratively updated by solving the Karush–Kuhn–Tucker optimality conditions and using the conjugate gradient method with an inexact line search. Various analysis conditions such as regularization scheme, number of electrodes, current input patterns, and electrode arrangement were set differently, and the corresponding results were compared. It was found from this study that the proposed EIT method yielded appropriate inversion results with various parameter settings, and the optimal implementation parameters of the EIT method are presented. This study is expected to expand the utility and applicability of EIT for the non-destructive evaluation of structures

Associations between Melatonin, Neuroinflammation, and Brain Alterations in Depression

Pro-inflammatory systemic conditions that can cause neuroinflammation and subsequent alterations in brain regions involved in emotional regulation have been suggested as an underlying mechanism for the pathophysiology of major depressive disorder (MDD). A prominent feature of MDD is disruption of circadian rhythms, of which melatonin is considered a key moderator, and alterations in the melatonin system have been implicated in MDD. Melatonin is involved in immune system regulation and has been shown to possess anti-inflammatory properties in inflammatory conditions, through both immunological and non-immunological actions. Melatonin has been suggested as a highly cytoprotective and neuroprotective substance and shown to stimulate all stages of neuroplasticity in animal models. The ability of melatonin to suppress inflammatory responses through immunological and non-immunological actions, thus influencing neuroinflammation and neurotoxicity, along with subsequent alterations in brain regions that are implicated in depression, can be demonstrated by the antidepressant-like effects of melatonin. Further studies that investigate the associations between melatonin, immune markers, and alterations in the brain structure and function in patients with depression could identify potential MDD biomarkers

MnNH4P2O7-Based Coating for High Temperature Assessment on the Surfaces of Cement Composites

This study examines the implementation of an MnNH4P2O7 (ammonium manganese III pyrophosphate)-based coating on structural elements to obtain temperature information with color changes. Based on the MnNH4P2O7 material, a coating was prepared and deposited on cement mortar surfaces. Heat experiments were then conducted to evaluate the thermochromism on the fabricated samples. The coated samples exhibited a superior irreversible thermochromic property at 400 °C with a color change from dark violet to light grayish blue at the heated surface. The color changes were retrieved at each temperature using a digital camera, and the change in color properties was evaluated in the RGB and L*a*b* color spaces using image processing techniques. With increasing temperature from room temperature, the RGB values were almost constant until 200 °C. At higher temperatures, the color changes started to accelerate until 400 °C. The values showed a 167%, 567%, and 49% increase in R, G, and B values, respectively, at 400 °C. In the L*a*b* color space, when the temperature was increased from room temperature to 400 °C, the L*a*b* values showed an increase of 211%, a decrease of 94%, and an increase of 78%, respectively

The Efficiency Analysis of National R&D Planning for the Field of Precision Medicine in Korea

Precision medicine has received a lot of attention in recent years and we have not yet found any research cases that apply Data Envelopment Analysis (DEA) to investment decision making in this area. The purpose of this study is to analyze the relative efficiency of candidate technology sectors in order to determine priorities for government investment in precision medicine. The results of the efficiency analysis can be used as an important reference for government policy makers to determine the amount of government investment in the next year for each candidate technology sector. The candidate technology for government investment in precision medicine was decided for 23 sectors based on the data analysis and the opinions of expert committees. This study applies the input-oriented DEA in regard to 23 technology sectors, which is widely used to analyze relative efficiency in terms of inputs versus outputs and to enhance efficiency through the propositional reduction of inputs. The input variables include the government’s research and development (R&D) investment and forward and backward industry linkage effects. The output variables are the employment creation effect, value-added effect, number of Korean patents, and number of Korean papers. Our analysis results show that the 23 technology sectors in precision medicine overall have a high efficiency, with the exception of the biobank technology sector. Therefore, since the Biobank technology sector has strong infrastructure characteristics, it seems to require continuous investment. The efficiency of DEA is high in most precision medicine sectors; therefore, overall, investing in these technologies is expected to yield good benefits

A Cytoplasmic Heme Sensor Illuminates the Impacts of Mitochondrial and Vacuolar Functions and Oxidative Stress on Heme-Iron Homeostasis in Cryptococcus neoformans

Invasive fungal diseases are increasing in frequency, and new drug targets and antifungal drugs are needed to bolster therapy. The mechanisms by which pathogens obtain critical nutrients such as iron from heme during host colonization represent a promising target for therapy. In this study, we employed a fluorescent heme sensor to investigate heme homeostasis in Cryptococcus neoformans. We demonstrated that endocytosis is a key aspect of heme acquisition and that vacuolar and mitochondrial functions are important in regulating the pool of available heme in cells. Stress generated by oxidative conditions impacts the heme pool, as do the drugs artemisinin and metformin; these drugs have heme-related activities and are in clinical use for malaria and diabetes, respectively. Overall, our study provides insights into mechanisms of fungal heme acquisition and demonstrates the utility of the heme sensor for drug characterization in support of new therapies for fungal diseases.Pathogens must compete with hosts to acquire sufficient iron for proliferation during pathogenesis. The pathogenic fungus Cryptococcus neoformans is capable of acquiring iron from heme, the most abundant source in vertebrate hosts, although the mechanisms of heme sensing and acquisition are not entirely understood. In this study, we adopted a chromosomally encoded heme sensor developed for Saccharomyces cerevisiae to examine cytosolic heme levels in C. neoformans using fluorescence microscopy, fluorimetry, and flow cytometry. We validated the responsiveness of the sensor upon treatment with exogenous hemin, during proliferation in macrophages, and in strains defective for endocytosis. We then used the sensor to show that vacuolar and mitochondrial dysregulation and oxidative stress reduced the labile heme pool in the cytosol. Importantly, the sensor provided a tool to further demonstrate that the drugs artemisinin and metformin have heme-related activities and the potential to be repurposed for antifungal therapy. Overall, this study provides insights into heme sensing by C. neoformans and establishes a powerful tool to further investigate mechanisms of heme-iron acquisition in the context of fungal pathogenesis