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      Pathways to depressive and anxiety disorders during and after the COVID-19 pandemic

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      a , b , a , b
      The Lancet. Psychiatry
      Elsevier Ltd.

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          Abstract

          The Global Burden of Disease (GBD) data for 2020 from 204 countries indicates that the COVID-19 pandemic and associated lockdowns increased the prevalence of anxiety and depressive disorders worldwide. 1 Two key factors behind these increases were identified: infection rate and immobility. 1 Here we present a conceptual model that provides insight into the processes that underlie how these factors operate and can help to predict the long-term effects of the factors. The effect of infection rate and immobility on depressive and anxiety disorders is shown in the figure. (In the GBD study, 1 infection rate was used as a proxy factor for the psychological effects [eg, fear of infection] of the pandemic and the physiological effects [eg, nervous system impairment 2 ] of COVID-19.) The findings of the GBD study suggest that lockdowns, by decreasing the number of infections, can indirectly help to reduce the prevalence of anxiety disorders and depressive disorders (figure ). Figure A conceptual model of the effects of the COVID-19 pandemic and lockdowns on depressive and anxiety disorders The effects of the COVID-19 pandemic (grey) include a higher prevalence of depressive and anxiety disorders (1a,b). These disorders can also lead to more severe SARS-CoV-2 infections and increased mortality (2a,b). The beneficial effects of lockdowns (green) include fewer infections and reduced mortality, leading to fewer depressive and anxiety disorders (3a–c). Harmful effects of lockdowns (red) include immobility, leading to more depressive and anxiety disorders (4a–c), which then, in turn, increase immobility (5a,b). These disorders are also highly comorbid (6a,b) and are likely to relapse (7a,b). However, any positive short-term effects of lockdowns on mental health (eg, due to safety behaviours, such as avoiding social contact and feeling less anxiety as a result) are likely to become counterproductive in the longer term (eg, social anxiety). Lockdowns decrease mobility, leading to a reduction in physical activity, social isolation, disruption of school and work-related activities, reduced peer interaction and learning, and restricted access to (mental) health care. 1 The immobility resulting from the lockdowns was associated with an increased prevalence of depressive and anxiety disorders in the GBD study (figure). 1 Therefore, lockdowns seem to have both advantageous and disadvantageous effects: by lowering infection rates, they might reduce the prevalence of depressive and anxiety disorders, but lockdowns are also likely to increase the prevalence of these disorders owing to the resulting immobility (figure). Future research on interventions to mitigate the adverse effects of lockdowns or other types of emergency policy on mental health could examine which elements of immobility are particularly harmful, and how to alleviate them. Because depressive and anxiety disorders undermine general health, they can amplify the effects of SARS-CoV-2 infection.3, 4 Infection severity and mortality rates are likely to be higher in people with depression and anxiety as a result of compromised immune system functioning in these disorders,3, 4 leading to a reinforcing feedback loop between the increased infection rates and the disorders (figure). Similarly, because depressive disorders and some anxiety disorders impair daily functioning, people with these disorders might have greater immobility than the general population—for instance, due to low energy, social withdrawal, or fear of leaving their houses. This can result in reinforcing feedback loops between increased immobility and the disorders (figure), which are likely to remain after the lockdowns are lifted and the pandemic is over. Depressive and anxiety disorders are also highly comorbid. 5 These disorders can form another feedback loop in which they can trigger and reinforce each other (figure). Such a loop is highly likely to operate during and after the lockdowns and the pandemic. Finally, depressive and anxiety disorders are highly recurrent: 6 individuals with major depressive disorder are estimated to have seven episodes throughout their lives. 7 Both depressive and anxiety disorders can be risk factors for a subsequent episode, creating their own individual reinforcing feedback loops (figure) that can operate over months or years, leading to more mental health problems even after the lockdowns and the pandemic are long gone. After the COVID-19 pandemic is over, affected individuals will most likely not return to their normal (mental) lives. 8 As we aim to show with our conceptual model, common mental disorders can take a long time to subside because their strong self-reinforcing mechanisms can keep individuals trapped in complex, reinforcing negative cycles long after the triggering cause has disappeared. 9 Moreover, because a previous episode is among the largest risk factors for depression 9 and anxiety disorders, 10 millions of individuals who have had these conditions during the pandemic will have them again—and multiple times—during their lives. COVID-19 will therefore have changed the mental health landscape of the coming decades. Insights from research such as the GBD study outline environmental pathways that lead to depressive and anxiety disorders and help to identify reinforcing loops that keep individuals vulnerable during societally challenging times. With this emerging knowledge, we can identify new target points for interventions and inform policymakers of the risk factors. This will, in turn, enable us to prevent and treat mental health problems more effectively during any future pandemics or other societal crises involving immobility and heightened concern for one's safety, such as war. We declare no competing interests. Research in the Amsterdam UMC and the Centre for Urban Mental Health is funded by the University of Amsterdam. The funding bodies had had no direct involvement in the conceptualisation or the writing of the manuscript.

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          Neurologic Manifestations of Hospitalized Patients With Coronavirus Disease 2019 in Wuhan, China

          The outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China, is serious and has the potential to become an epidemic worldwide. Several studies have described typical clinical manifestations including fever, cough, diarrhea, and fatigue. However, to our knowledge, it has not been reported that patients with COVID-19 had any neurologic manifestations.
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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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              Psychiatric and neuropsychiatric presentations associated with severe coronavirus infections: a systematic review and meta-analysis with comparison to the COVID-19 pandemic

              Summary Background Before the COVID-19 pandemic, coronaviruses caused two noteworthy outbreaks: severe acute respiratory syndrome (SARS), starting in 2002, and Middle East respiratory syndrome (MERS), starting in 2012. We aimed to assess the psychiatric and neuropsychiatric presentations of SARS, MERS, and COVID-19. Methods In this systematic review and meta-analysis, MEDLINE, Embase, PsycINFO, and the Cumulative Index to Nursing and Allied Health Literature databases (from their inception until March 18, 2020), and medRxiv, bioRxiv, and PsyArXiv (between Jan 1, 2020, and April 10, 2020) were searched by two independent researchers for all English-language studies or preprints reporting data on the psychiatric and neuropsychiatric presentations of individuals with suspected or laboratory-confirmed coronavirus infection (SARS coronavirus, MERS coronavirus, or SARS coronavirus 2). We excluded studies limited to neurological complications without specified neuropsychiatric presentations and those investigating the indirect effects of coronavirus infections on the mental health of people who are not infected, such as those mediated through physical distancing measures such as self-isolation or quarantine. Outcomes were psychiatric signs or symptoms; symptom severity; diagnoses based on ICD-10, DSM-IV, or the Chinese Classification of Mental Disorders (third edition) or psychometric scales; quality of life; and employment. Both the systematic review and the meta-analysis stratified outcomes across illness stages (acute vs post-illness) for SARS and MERS. We used a random-effects model for the meta-analysis, and the meta-analytical effect size was prevalence for relevant outcomes, I 2 statistics, and assessment of study quality. Findings 1963 studies and 87 preprints were identified by the systematic search, of which 65 peer-reviewed studies and seven preprints met inclusion criteria. The number of coronavirus cases of the included studies was 3559, ranging from 1 to 997, and the mean age of participants in studies ranged from 12·2 years (SD 4·1) to 68·0 years (single case report). Studies were from China, Hong Kong, South Korea, Canada, Saudi Arabia, France, Japan, Singapore, the UK, and the USA. Follow-up time for the post-illness studies varied between 60 days and 12 years. The systematic review revealed that during the acute illness, common symptoms among patients admitted to hospital for SARS or MERS included confusion (36 [27·9%; 95% CI 20·5–36·0] of 129 patients), depressed mood (42 [32·6%; 24·7–40·9] of 129), anxiety (46 [35·7%; 27·6–44·2] of 129), impaired memory (44 [34·1%; 26·2–42·5] of 129), and insomnia (54 [41·9%; 22·5–50·5] of 129). Steroid-induced mania and psychosis were reported in 13 (0·7%) of 1744 patients with SARS in the acute stage in one study. In the post-illness stage, depressed mood (35 [10·5%; 95% CI 7·5–14·1] of 332 patients), insomnia (34 [12·1%; 8·6–16·3] of 280), anxiety (21 [12·3%; 7·7–17·7] of 171), irritability (28 [12·8%; 8·7–17·6] of 218), memory impairment (44 [18·9%; 14·1–24·2] of 233), fatigue (61 [19·3%; 15·1–23·9] of 316), and in one study traumatic memories (55 [30·4%; 23·9–37·3] of 181) and sleep disorder (14 [100·0%; 88·0–100·0] of 14) were frequently reported. The meta-analysis indicated that in the post-illness stage the point prevalence of post-traumatic stress disorder was 32·2% (95% CI 23·7–42·0; 121 of 402 cases from four studies), that of depression was 14·9% (12·1–18·2; 77 of 517 cases from five studies), and that of anxiety disorders was 14·8% (11·1–19·4; 42 of 284 cases from three studies). 446 (76·9%; 95% CI 68·1–84·6) of 580 patients from six studies had returned to work at a mean follow-up time of 35·3 months (SD 40·1). When data for patients with COVID-19 were examined (including preprint data), there was evidence for delirium (confusion in 26 [65%] of 40 intensive care unit patients and agitation in 40 [69%] of 58 intensive care unit patients in one study, and altered consciousness in 17 [21%] of 82 patients who subsequently died in another study). At discharge, 15 (33%) of 45 patients with COVID-19 who were assessed had a dysexecutive syndrome in one study. At the time of writing, there were two reports of hypoxic encephalopathy and one report of encephalitis. 68 (94%) of the 72 studies were of either low or medium quality. Interpretation If infection with SARS-CoV-2 follows a similar course to that with SARS-CoV or MERS-CoV, most patients should recover without experiencing mental illness. SARS-CoV-2 might cause delirium in a significant proportion of patients in the acute stage. Clinicians should be aware of the possibility of depression, anxiety, fatigue, post-traumatic stress disorder, and rarer neuropsychiatric syndromes in the longer term. Funding Wellcome Trust, UK National Institute for Health Research (NIHR), UK Medical Research Council, NIHR Biomedical Research Centre at University College London Hospitals NHS Foundation Trust and University College London.
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                Author and article information

                Journal
                Lancet Psychiatry
                Lancet Psychiatry
                The Lancet. Psychiatry
                Elsevier Ltd.
                2215-0366
                2215-0374
                16 June 2022
                July 2022
                16 June 2022
                : 9
                : 7
                : 531-533
                Affiliations
                [a ]Centre for Urban Mental Health, University of Amsterdam, Amsterdam, Netherlands
                [b ]Department of Psychiatry, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands
                Article
                S2215-0366(22)00152-3
                10.1016/S2215-0366(22)00152-3
                9212978
                35717953
                e0a2065c-57d8-4103-a551-665da404f870
                © 2022 Elsevier Ltd. All rights reserved.

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