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      Precision psychiatry and Research Domain Criteria: Implications for clinical trials and future practice

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          Abstract

          Psychiatric disorders are associated with significant social and economic burdens, many of which are related to issues with current diagnosis and treatments. The coronavirus (COVID-19) pandemic is estimated to have increased the prevalence and burden of major depressive and anxiety disorders, indicating an urgent need to strengthen mental health systems globally. To date, current approaches adopted in drug discovery and development for psychiatric disorders have been relatively unsuccessful. Precision psychiatry aims to tailor healthcare more closely to the needs of individual patients and, when informed by neuroscience, can offer the opportunity to improve the accuracy of disease classification, treatment decisions, and prevention efforts. In this review, we highlight the growing global interest in precision psychiatry and the potential for the National Institute of Health-devised Research Domain Criteria (RDoC) to facilitate the implementation of transdiagnostic and improved treatment approaches. The need for current psychiatric nosology to evolve with recent scientific advancements and increase awareness in emerging investigators/clinicians of the value of this approach is essential. Finally, we examine current challenges and future opportunities of adopting the RDoC-associated translational and transdiagnostic approaches in clinical studies, acknowledging that the strength of RDoC is that they form a dynamic framework of guiding principles that is intended to evolve continuously with scientific developments into the future. A collaborative approach that recruits expertise from multiple disciplines, while also considering the patient perspective, is needed to pave the way for precision psychiatry that can improve the prognosis and quality of life of psychiatric patients.

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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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            Global, regional, and national burden of 12 mental disorders in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

            (2022)
            Summary Background The mental disorders included in the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 were depressive disorders, anxiety disorders, bipolar disorder, schizophrenia, autism spectrum disorders, conduct disorder, attention-deficit hyperactivity disorder, eating disorders, idiopathic developmental intellectual disability, and a residual category of other mental disorders. We aimed to measure the global, regional, and national prevalence, disability-adjusted life-years (DALYS), years lived with disability (YLDs), and years of life lost (YLLs) for mental disorders from 1990 to 2019. Methods In this study, we assessed prevalence and burden estimates from GBD 2019 for 12 mental disorders, males and females, 23 age groups, 204 countries and territories, between 1990 and 2019. DALYs were estimated as the sum of YLDs and YLLs to premature mortality. We systematically reviewed PsycINFO, Embase, PubMed, and the Global Health Data Exchange to obtain data on prevalence, incidence, remission, duration, severity, and excess mortality for each mental disorder. These data informed a Bayesian meta-regression analysis to estimate prevalence by disorder, age, sex, year, and location. Prevalence was multiplied by corresponding disability weights to estimate YLDs. Cause-specific deaths were compiled from mortality surveillance databases. The Cause of Death Ensemble modelling strategy was used to estimate death rate by age, sex, year, and location. The death rates were multiplied by the years of life expected to be remaining at death based on a normative life expectancy to estimate YLLs. Deaths and YLLs could be calculated only for anorexia nervosa and bulimia nervosa, since these were the only mental disorders identified as underlying causes of death in GBD 2019. Findings Between 1990 and 2019, the global number of DALYs due to mental disorders increased from 80·8 million (95% uncertainty interval [UI] 59·5–105·9) to 125·3 million (93·0–163·2), and the proportion of global DALYs attributed to mental disorders increased from 3·1% (95% UI 2·4–3·9) to 4·9% (3·9–6·1). Age-standardised DALY rates remained largely consistent between 1990 (1581·2 DALYs [1170·9–2061·4] per 100 000 people) and 2019 (1566·2 DALYs [1160·1–2042·8] per 100 000 people). YLDs contributed to most of the mental disorder burden, with 125·3 million YLDs (95% UI 93·0–163·2; 14·6% [12·2–16·8] of global YLDs) in 2019 attributable to mental disorders. Eating disorders accounted for 17 361·5 YLLs (95% UI 15 518·5–21 459·8). Globally, the age-standardised DALY rate for mental disorders was 1426·5 (95% UI 1056·4–1869·5) per 100 000 population among males and 1703·3 (1261·5–2237·8) per 100 000 population among females. Age-standardised DALY rates were highest in Australasia, Tropical Latin America, and high-income North America. Interpretation GBD 2019 showed that mental disorders remained among the top ten leading causes of burden worldwide, with no evidence of global reduction in the burden since 1990. The estimated YLLs for mental disorders were extremely low and do not reflect premature mortality in individuals with mental disorders. Research to establish causal pathways between mental disorders and other fatal health outcomes is recommended so that this may be addressed within the GBD study. To reduce the burden of mental disorders, coordinated delivery of effective prevention and treatment programmes by governments and the global health community is imperative. Funding Bill & Melinda Gates Foundation, Australian National Health and Medical Research Council, Queensland Department of Health, Australia.
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              Alzheimer Disease: An Update on Pathobiology and Treatment Strategies

              Alzheimer disease (AD) is a heterogeneous disease with a complex pathobiology. The presence of extracellular amyloid-β deposition as neuritic plaques and intracellular accumulation of hyperphosphorylated tau as neurofibrillary tangles remain the primary neuropathologic criteria for AD diagnosis. However, a number of recent fundamental discoveries highlight important pathological roles for other critical cellular and molecular processes. Despite this, no disease modifying treatment currently exists and numerous phase 3 clinical trials have failed to demonstrate benefit. We review here recent advances in our understanding of AD pathobiology and discuss current treatment strategies, highlighting recent clinical trials and opportunities for developing future disease modifying therapies.
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                Author and article information

                Contributors
                (View ORCID Profile)
                Journal
                CNS Spectrums
                CNS Spectr.
                Cambridge University Press (CUP)
                1092-8529
                2165-6509
                February 2024
                September 07 2023
                February 2024
                : 29
                : 1
                : 26-39
                Article
                10.1017/S1092852923002420
                03ebea0e-ff84-4c09-a845-fa33ed8ed4d2
                © 2024

                http://creativecommons.org/licenses/by/4.0

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