COVID-19-induced anxiety,depression and stress among healthcare professionals in Sri Lanka

Objective:To assess the degree of anxiety,depression and stress due to the COVID-19 epidemic among healthcare professionals in Sri Lanka.Methods:Healthcare professionals from 6 selected government and private hospitals located in Gampaha District were recruited for the study.The socio-demographic factors,knowledge and attitudes of healthcare professionals on COVID-19 was collected through a self-administered questionnaire,while Depression,Anxiety and Stress Scale score was used to assess the psychological wellbeing.Descriptive statistics and binary logistic regression techniques were used for data analysis.Results:Totally 324 healthcare professionals were included and the respondents had a high overall level of knowledge towards COVID-19.Twenty-five percent of the respondents had different levels of anxiety,while 10.8%had mild depression,and 4.6%had moderate depression.Interestingly,40.4%of the respondents had mild stress,and 11.1%had moderate stress.Young people(20-35 years),medical laboratory technologist and nursing officer,being quarantined,having a SARS-CoV-2-infected family member,involvement in COVID-19 patient care,and limited availability of personal protection equipment,were recognized as significant risk factors associated with anxiety,depression and stress.Conclusions:The healthcare professionals are high-risk groups to experience psychological impacts from COVID-19.Continuous monitoring and implementing appropriate intervention activities and provision of counseling support are highly recommended.

Chronic stress causes protein kinase C epsilon-aldehyde dehydrogenase 2 signaling pathway perturbation in the rat hippocampus and prefrontal cortex,but not in the myocardium

Chronic stress is strongly associated with the occurrence and development of depression and cardiovascular disease.Stress can induce altered mitochondrial function and activation of apoptosis in the cardio-cerebral system.However,it is unknown whether the protein kinase C ε（PKCε）-aldehyde dehydrogenase 2（ALDH2） pathway is altered under chronic stress,and this study sought to address this question.A rat model of depression was established using a chronic unpredictable mild stress（CUMS） protocol.After experiencing CUMS for 4 weeks,the sucrose preference test and the forced swim test verified depressive-like behaviors.Enzyme linked immunosorbent assays showed that ALDH2 activity was decreased in the rat hippocampus and prefrontal cortex,but was not altered in the myocardium.Western blot assays demonstrated reduced levels of ALDH2 and PKCε,but increased levels of 4-hydroxy-2-nonenal（4 HNE） adducts.Caspase-3 expression did not obviously alter,but active forms of caspase-3 were increased in the hippocampus and prefrontal cortex.In the myocardium,expression of ALDH2,PKCε and 4 HNE adducts did not remarkably alter;while caspase-3 expression was reduced and the active forms of caspase-3 were upregulated.Pearson＇s correlation test demonstrated that expression of 4 HNE adducts was positively correlated with levels of the active forms of caspase-3 in the hippocampus and prefrontal cortex,but not in the myocardium.In conclusion,chronic stress can damage the PKCε-ALDH2 signaling pathway in the hippocampus and prefrontal cortex,but not in the myocardium.Moreover,4 HNE is associated with active forms of caspase-3 in the hippocampus and prefrontal cortex.

Generalized stress field in granular soils heap with RayleigheRitz method

The stress field in granular soils heap(including piled coal) will have a non-negligible impact on the settlement of the underlying soils. It is usually obtained by measurements and numerical simulations.Because the former method is not reliable as pressure cells instrumented on the interface between piled coal and the underlying soft soil do not work well, results from numerical methods alone are necessary to be doubly checked with one more method before they are extended to more complex cases. The generalized stress field in granular soils heap is analyzed with Rayleighe Ritz method. The problem is divided into two cases: case A without horizontal constraint on the base and case B with horizontal constraint on the base. In both cases, the displacement functions u(x, y) and v(x, y) are assumed to be cubic polynomials with 12 undetermined parameters, which will satisfy the Cauchy’s partial differential equations, generalized Hooke’s law and boundary equations. A function is built with the Rayleighe Ritz method according to the principle of minimum potential energy, and the problem is converted into solving two undetermined parameters through the variation of the function, while the other parameters are expressed in terms of these two parameters. By comparison of results from the Rayleighe Ritz method and numerical simulations, it is demonstrated that the Rayleighe Ritz method is feasible to study the generalized stress field in granular soils heap. Solutions from numerical methods are verified before being extended to more complicated cases.

Molecular mechanism of noradrenaline during the stress-induced major depressive disorder

Chronic stress-induced depression is a common hallmark of many psychiatric disorders with high morbidity rate.Stress-induced dysregulation of noradrenergic system has been implicated in the pathogenesis of depression.Lack of monoamine in the brain has been believed to be the main causative factor behind pathophysiology of major depressive disorder（MDD） and several antidepressants functions by increasing the monoamine level at the synapses in the brain.However,it is undetermined whether the noradrenergic receptor stimulation is critical for the therapeutic effect of antidepressant.Contrary to noradrenergic receptor stimulation,it has been suggested that the desensitization of β-adrenoceptor is involved in the therapeutic effect of antidepressant.In addition,enhanced noradrenaline（NA） release is central response to stress and thought to be a risk factor for the development of MDD.Moreover,fast acting antidepressant suppresses the hyperactivation of noradrenergic neurons in locus coeruleus（LC）.However,it is unclear how they alter the firing activity of LC neurons.These inconsistent reports about antidepressant effect of NA-reuptake inhibitors（NRIs） and enhanced release of NA as a stress response complicate our understanding about the pathophysiology of MDD.In this review,we will discuss the role of NA in pathophysiology of stress and the mechanism of therapeutic effect of NA in MDD.We will also discuss the possible contributions of each subtype of noradrenergic receptors on LC neurons,hypothalamic-pituitary-adrenal axis（HPA-axis） and brain derived neurotrophic factor-induced hippocampal neurogenesis during stress and therapeutic effect of NRIs in MDD.

Electroacupuncture pretreatment exhibits antidepressive effects by regulating hippocampal proteomics in rats with chronic restraint stress

The clinical effect of electroacupuncture on depression is widely recognized. However, the signal transduction pathways and target proteins involved remain unclear. In the present study, rat models of chronic restraint stress were used to explore the mechanism by which electroacupuncture alleviates depression. Rats were randomly divided into control, model, and electroacupuncture groups. Chronic restraint stress was induced in the model and electroacupuncture groups by restraining rats for 28 days. In the electroacupuncture group, electroacupuncture pretreatment at Baihui（GV20） and Yintang（GV29） acupoints was performed daily（1 m A, 2 Hz, discontinuous wave, 20 minutes） prior to restraint for 28 days. Open field tests and body weight measurements were carried out to evaluate the depressive symptoms at specific time points. On day 28, the crossing number, rearing number, and body weights of the model group were significantly lower than those in the control group. Behavior test results indicated that rat models of depressive-like symptoms were successfully established by chronic restraint stress combined with solitary raising. On day 28, an isobaric tag for a relative and absolute quantitation-based quantitative proteomic approach was performed to identify differentially expressed proteins in hippocampal samples obtained from the model and electroacupuncture groups. The potential function of these differential proteins was predicted through the use of the Cluster of Orthologous Groups of proteins（COG） database. Twenty-seven differential proteins（uncharacteristic proteins expected） were selected from the model and electroacupuncture groups. In addition to unknown protein functions, COG are mainly concentrated in general prediction function, mechanism of signal transduction, amino acid transport and metabolism groups. This suggests that electroacupuncture improved depressive-like symptoms by regulating differential proteins, and most of these related proteins exist in nerve cells.

Association between Perceived Stressfulness of Stressful Life Events and the Suicidal Risk in Chinese Patients with Major Depressive Disorder

Background： Patients with major depressive disorder （MDD） usually have high risk of suicidality. Few studies have investigated the effects of stressful life events （SLEs） on the risk of suicide in Chinese patients who have developed MDD. This study aimed to investigate the impact of SLEs on suicidal risk in Chinese patients with MDD. Methods： In total, 1029 patients with MDD were included from nine psychiatric hospitals to evaluate the impact of SLEs on suicidal risk. Patients fulfilling the Mini-International Neuropsychiatric Interview （MINI） criteria for MDD were included in the study. Patients were excluded if they had lifetime or current diagnoses of psychotic disorder, bipolar disorder, and alcohol or substance dependence. Depressive symptoms were assessed by the 17-item Harnilton Depression Scale （HAMD-17）. The suicidal risk of MDD patients was determined by the suicide risk module of MINI. SLEs were assessed by the Life Events Scale. Results： No gender difference was found for suicidal risk in MDD patients. Patients with suicidal risk had younger ages, lower education levels, more drinking behavior, and lower marriage rate, and fewer people had child and more severe depressive symptoms than nonsuicidal risk group. High-level perceived stressfulness （HPS） and number of SLEs that patients were exposed to were significantly greater in patients with suicidal risk than patients without. In multivariate logistic analysis, HPS of SLEs （odds ratio [OR] = 1.54, 95% confidence interval [C1]： 1.16-2.05, P = 0.003） and depressive symptoms （OR = 1.08.95% CI： 1.05-1.11, P 〈 0.001 ） were associated with suicidal risk even after adjustment of gender, age, marriage, drinking behavior, and childless. Conclusions： HPS of SLEs is associated with suicide risk in Chinese patients with MDD. Further suicide prevention programs targeting this risk factor are needed. Trial Registration： ClinicalTrials.gov： NCT02023567; https：//clinicaltrials.gov/ct2/show/NCTO2023567？term=NCTO2023567＆rank=l.

Rapid-onset antidepressant efficacy of glutamatergic system modulators:The neural plasticity hypothesis of depression

Depression is a devastating psychiatric disorder widely attributed to defi cient monoaminergic signaling in the central nervous system. However,most clinical antidepressants enhance monoaminergic neurotransmission with little delay but require 4-8 weeks to reach therapeutic efficacy,a paradox suggesting that the monoaminergic hypothesis of depression is an oversimplifi cation. In contrast to the antidepressants targeting the monoaminergic system,a single dose of the N-methyl-D-aspartate receptor（NMDAR） antagonist ketamine produces rapid（within 2 h） and sustained（over 7 days） antidepressant effi cacy in treatment-resistant patients. Glutamatergic transmission mediated by NMDARs is critical for experience-dependent synaptic plasticity and learning,processes that can be modifi ed indirectly by the monoaminergic system. To better understand the mechanisms of action of the new antidepressants like ketamine,we review and compare the monoaminergic and glutamatergic antidepressants,with emphasis on neural plasticity. The pathogenesis of depression may involve maladaptive neural plasticity in glutamatergic circuits that may serve as a new class of targets to produce rapid antidepressant effects.