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      Recent advances in anxiety disorders: Focus on animal models and pathological mechanisms

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          Abstract

          Anxiety disorders have become one of the most severe psychiatric disorders, and the incidence is increasing every year. They impose an extraordinary personal and socioeconomic burden. Anxiety disorders are influenced by multiple complex and interacting genetic, psychological, social, and environmental factors, which contribute to disruption or imbalance in homeostasis and eventually cause pathologic anxiety. The selection of a suitable animal model is important for the exploration of disease etiology and pathophysiology, and the development of new drugs. Therefore, a more comprehensive understanding of the advantages and limitations of existing animal models of anxiety disorders is helpful to further study the underlying pathological mechanisms of the disease. This review summarizes animal models and the pathogenesis of anxiety disorders, and discusses the current research status to provide insights for further study of anxiety disorders.

          Abstract

          This review mainly summarizes the existing animal models and the latest progress of pathological mechanisms of anxiety disorders. In this manuscript, the advantages and disadvantages of existing animal models of anxiety and behavioral evaluation methods are discussed. Meanwhile, the recent pathological mechanisms of anxiety disorders are explored from multiple perspectives, including neuroendocrine, ion channel, endocannabinoid system, neural circuits and so on.

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          Global prevalence and burden of depressive and anxiety disorders in 204 countries and territories in 2020 due to the COVID-19 pandemic

          (2021)
          Background Before 2020, mental disorders were leading causes of the global health-related burden, with depressive and anxiety disorders being leading contributors to this burden. The emergence of the COVID-19 pandemic has created an environment where many determinants of poor mental health are exacerbated. The need for up-to-date information on the mental health impacts of COVID-19 in a way that informs health system responses is imperative. In this study, we aimed to quantify the impact of the COVID-19 pandemic on the prevalence and burden of major depressive disorder and anxiety disorders globally in 2020. Methods We conducted a systematic review of data reporting the prevalence of major depressive disorder and anxiety disorders during the COVID-19 pandemic and published between Jan 1, 2020, and Jan 29, 2021. We searched PubMed, Google Scholar, preprint servers, grey literature sources, and consulted experts. Eligible studies reported prevalence of depressive or anxiety disorders that were representative of the general population during the COVID-19 pandemic and had a pre-pandemic baseline. We used the assembled data in a meta-regression to estimate change in the prevalence of major depressive disorder and anxiety disorders between pre-pandemic and mid-pandemic (using periods as defined by each study) via COVID-19 impact indicators (human mobility, daily SARS-CoV-2 infection rate, and daily excess mortality rate). We then used this model to estimate the change from pre-pandemic prevalence (estimated using Disease Modelling Meta-Regression version 2.1 [known as DisMod-MR 2.1]) by age, sex, and location. We used final prevalence estimates and disability weights to estimate years lived with disability and disability-adjusted life-years (DALYs) for major depressive disorder and anxiety disorders. Findings We identified 5683 unique data sources, of which 48 met inclusion criteria (46 studies met criteria for major depressive disorder and 27 for anxiety disorders). Two COVID-19 impact indicators, specifically daily SARS-CoV-2 infection rates and reductions in human mobility, were associated with increased prevalence of major depressive disorder (regression coefficient [ B ] 0·9 [95% uncertainty interval 0·1 to 1·8; p=0·029] for human mobility, 18·1 [7·9 to 28·3; p=0·0005] for daily SARS-CoV-2 infection) and anxiety disorders (0·9 [0·1 to 1·7; p=0·022] and 13·8 [10·7 to 17·0; p<0·0001]. Females were affected more by the pandemic than males ( B 0·1 [0·1 to 0·2; p=0·0001] for major depressive disorder, 0·1 [0·1 to 0·2; p=0·0001] for anxiety disorders) and younger age groups were more affected than older age groups (−0·007 [–0·009 to −0·006; p=0·0001] for major depressive disorder, −0·003 [–0·005 to −0·002; p=0·0001] for anxiety disorders). We estimated that the locations hit hardest by the pandemic in 2020, as measured with decreased human mobility and daily SARS-CoV-2 infection rate, had the greatest increases in prevalence of major depressive disorder and anxiety disorders. We estimated an additional 53·2 million (44·8 to 62·9) cases of major depressive disorder globally (an increase of 27·6% [25·1 to 30·3]) due to the COVID-19 pandemic, such that the total prevalence was 3152·9 cases (2722·5 to 3654·5) per 100 000 population. We also estimated an additional 76·2 million (64·3 to 90·6) cases of anxiety disorders globally (an increase of 25·6% [23·2 to 28·0]), such that the total prevalence was 4802·4 cases (4108·2 to 5588·6) per 100 000 population. Altogether, major depressive disorder caused 49·4 million (33·6 to 68·7) DALYs and anxiety disorders caused 44·5 million (30·2 to 62·5) DALYs globally in 2020. Interpretation This pandemic has created an increased urgency to strengthen mental health systems in most countries. Mitigation strategies could incorporate ways to promote mental wellbeing and target determinants of poor mental health and interventions to treat those with a mental disorder. Taking no action to address the burden of major depressive disorder and anxiety disorders should not be an option. Funding Queensland Health, National Health and Medical Research Council, and the Bill and Melinda Gates Foundation.
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            Adult hippocampal neurogenesis buffers stress responses and depressive behavior

            Summary Glucocorticoids are released in response to stressful experiences and serve many beneficial homeostatic functions. However, dysregulation of glucocorticoids is associated with cognitive impairments and depressive illness 1, 2 . In the hippocampus, a brain region densely populated with receptors for stress hormones, stress and glucocorticoids strongly inhibit adult neurogenesis 3 . Decreased neurogenesis has been implicated in the pathogenesis of anxiety and depression, but direct evidence for this role is lacking 4, 5 . Here we show that adult-born hippocampal neurons are required for normal expression of the endocrine and behavioral components of the stress response. Using transgenic and radiation methods to specifically inhibit adult neurogenesis, we find that glucocorticoid levels are slower to recover after moderate stress and are less suppressed by dexamethasone in neurogenesis-deficient mice compared with intact mice, consistent with a role for the hippocampus in regulation of the hypothalamic-pituitary-adrenal (HPA) axis 6, 7 . Relative to controls, neurogenesis-deficient mice showed increased food avoidance in a novel environment after acute stress, increased behavioral despair in the forced swim test, and decreased sucrose preference, a measure of anhedonia. These findings identify a small subset of neurons within the dentate gyrus that are critical for hippocampal negative control of the HPA axis and support a direct role for adult neurogenesis in depressive illness.
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              Neuronal circuits for fear and anxiety.

              Decades of research has identified the brain areas that are involved in fear, fear extinction, anxiety and related defensive behaviours. Newly developed genetic and viral tools, optogenetics and advanced in vivo imaging techniques have now made it possible to characterize the activity, connectivity and function of specific cell types within complex neuronal circuits. Recent findings that have been made using these tools and techniques have provided mechanistic insights into the exquisite organization of the circuitry underlying internal defensive states. This Review focuses on studies that have used circuit-based approaches to gain a more detailed, and also more comprehensive and integrated, view on how the brain governs fear and anxiety and how it orchestrates adaptive defensive behaviours.

                Author and article information

                Contributors
                wangyh107@126.com
                Journal
                Animal Model Exp Med
                Animal Model Exp Med
                10.1002/(ISSN)2576-2095
                AME2
                Animal Models and Experimental Medicine
                John Wiley and Sons Inc. (Hoboken )
                2096-5451
                2576-2095
                28 November 2023
                December 2023
                : 6
                : 6 , Themed Issue: The role of Regulatory non‐coding RNA in human disease ( doiID: 10.1002/ame2.v6.6 )
                : 559-572
                Affiliations
                [ 1 ] Science & technology innovation center Hunan University of Chinese Medicine Changsha China
                Author notes
                [*] [* ] Correspondence

                Yuhong Wang, Science & technology innovation center, Hunan University of Chinese Medicine, Hunan, Changsha, 410208, China.

                Email: wangyh107@ 123456126.com

                Author information
                https://orcid.org/0009-0000-8708-0143
                Article
                AME212360 AMEM-2023-0065.R1
                10.1002/ame2.12360
                10757213
                38013621
                24df81cb-df93-4ad3-b701-f1efbf20e28f
                © 2023 The Authors. Animal Models and Experimental Medicine published by John Wiley & Sons Australia, Ltd on behalf of The Chinese Association for Laboratory Animal Sciences.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 13 July 2023
                : 09 October 2023
                Page count
                Figures: 5, Tables: 1, Pages: 14, Words: 10420
                Funding
                Funded by: National Natural Science Foundation of China , doi 10.13039/501100001809;
                Award ID: 82104793
                Award ID: 82104836
                Funded by: Natural Science Foundation of Hunan Province , doi 10.13039/501100004735;
                Award ID: 2023JJ60482
                Funded by: Open Foundation Project of TCM First‐class Disciplines in HNUCM
                Award ID: 2022ZYX18
                Funded by: Science and Technology talent promotion Project of Hunan Province
                Award ID: 2023TJ‐N22
                Categories
                Review
                Regular Articles
                Reviews
                Custom metadata
                2.0
                December 2023
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.3.6 mode:remove_FC converted:30.12.2023

                animal models,anxiety disorders,behavioral tests,mental diseases,pathogenesis

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