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      Immediate and long-term electrophysiological biomarkers of antidepressant-like behavioral effects after subanesthetic ketamine and medial prefrontal cortex deep brain stimulation treatment

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          Abstract

          Introduction

          Both ketamine (KET) and medial prefrontal cortex (mPFC) deep brain stimulation (DBS) are emerging therapies for treatment-resistant depression, yet our understanding of their electrophysiological mechanisms and biomarkers is incomplete. This study investigates aperiodic and periodic spectral parameters, and the signal complexity measure sample entropy, within mPFC local field potentials (LFP) in a chronic corticosterone (CORT) depression model after ketamine and/or mPFC DBS.

          Methods

          Male rats were intraperitoneally administered CORT or vehicle for 21 days. Over the last 7 days, animals receiving CORT were treated with mPFC DBS, KET, both, or neither; then tested across an array of behavioral tasks for 9 days.

          Results

          We found that the depression-like behavioral and weight effects of CORT correlated with a decrease in aperiodic-adjusted theta power (5–10 Hz) and an increase in sample entropy during the administration phase, and an increase in theta peak frequency and a decrease in the aperiodic exponent once the depression-like phenotype had been induced. The remission-like behavioral effects of ketamine alone correlated with a post-treatment increase in the offset and exponent, and decrease in sample entropy, both immediately and up to eight days post-treatment. The remission-like behavioral effects of mPFC DBS alone correlated with an immediate decrease in sample entropy, an immediate and sustained increase in low gamma (20–50 Hz) peak width and aperiodic offset, and sustained improvements in cognitive function. Failure to fully induce remission-like behavior in the combinatorial treatment group correlated with a failure to suppress an increase in sample entropy immediately after treatment.

          Conclusion

          Our findings therefore support the potential of periodic theta parameters as biomarkers of depression-severity; and periodic low gamma parameters and cognitive measures as biomarkers of mPFC DBS treatment efficacy. They also support sample entropy and the aperiodic spectral parameters as potential cross-modal biomarkers of depression severity and the therapeutic efficacy of mPFC DBS and/or ketamine. Study of these biomarkers is important as objective measures of disease severity and predictive measures of therapeutic efficacy can be used to personalize care and promote the translatability of research across studies, modalities, and species.

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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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              The novel object recognition memory: neurobiology, test procedure, and its modifications

              Animal models of memory have been considered as the subject of many scientific publications at least since the beginning of the twentieth century. In humans, memory is often accessed through spoken or written language, while in animals, cognitive functions must be accessed through different kind of behaviors in many specific, experimental models of memory and learning. Among them, the novel object recognition test can be evaluated by the differences in the exploration time of novel and familiar objects. Its application is not limited to a field of research and enables that various issues can be studied, such as the memory and learning, the preference for novelty, the influence of different brain regions in the process of recognition, and even the study of different drugs and their effects. This paper describes the novel object recognition paradigms in animals, as a valuable measure of cognition. The purpose of this work was to review the neurobiology and methodological modifications of the test commonly used in behavioral pharmacology.
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                Author and article information

                Contributors
                URI : https://loop.frontiersin.org/people/2388541/overviewRole: Role: Role: Role: Role: Role: Role: Role: Role: Role:
                Role: Role: Role: Role: Role:
                Role: Role: Role: Role: Role:
                Role: Role: Role: Role: Role: Role: Role:
                URI : https://loop.frontiersin.org/people/2726668/overviewRole: Role:
                Role: Role:
                Role: Role:
                URI : https://loop.frontiersin.org/people/2662553/overviewRole: Role:
                Role: Role:
                Role: Role:
                URI : https://loop.frontiersin.org/people/1619445/overviewRole: Role:
                URI : https://loop.frontiersin.org/people/1687053/overviewRole: Role:
                Role: Role:
                Role: Role: Role: Role: Role:
                Journal
                Front Neurosci
                Front Neurosci
                Front. Neurosci.
                Frontiers in Neuroscience
                Frontiers Media S.A.
                1662-4548
                1662-453X
                20 June 2024
                2024
                : 18
                : 1389096
                Affiliations
                [1] 1Department of Neurological Surgery, Keck School of Medicine, University of Southern California , Los Angeles, CA, United States
                [2] 2Neurorestoration Center, Keck School of Medicine, University of Southern California , Los Angeles, CA, United States
                [3] 3Department of Ophthalmology, Keck School of Medicine, University of Southern California , Los Angeles, CA, United States
                [4] 4Department of Psychiatry and Behavioral Sciences, Keck School of Medicine, University of Southern California , Los Angeles, CA, United States
                [5] 5Department of Bioengineering, University of California Riverside , Riverside, CA, United States
                [6] 6Rancho Los Amigos National Rehabilitation Center , Downey, CA, United States
                Author notes

                Edited by: Chuanliang Han, The Chinese University of Hong Kong, China

                Reviewed by: Kenji Hashimoto, Chiba University, Japan

                Brendon O. Watson, University of Michigan, United States

                Bin Wang, Capital Medical University, China

                *Correspondence: Matthew Bergosh, bergosh@ 123456usc.edu
                Article
                10.3389/fnins.2024.1389096
                11222339
                38966758
                fe950132-9a7e-46e4-bea1-3df7bd10694f
                Copyright © 2024 Bergosh, Medvidovic, Zepeda, Crown, Ipe, Debattista, Romero, Amjadi, Lam, Hakopian, Choi, Wu, Lo and Lee.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 20 February 2024
                : 07 May 2024
                Page count
                Figures: 6, Tables: 0, Equations: 0, References: 76, Pages: 16, Words: 13020
                Funding
                The author(s) declare that no financial support was received for the research, authorship, and/or publication of this article.
                Categories
                Neuroscience
                Original Research
                Custom metadata
                Translational Neuroscience

                Neurosciences
                electrophysiology,biomarker,depression,behavior,deep brain stimulation,ketamine,psychedelic,translational

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