The chronic neuropsychiatric sequelae of COVID-19: The need for a prospective study of viral impact on brain functioning.

INTRODUCTION: The increasing evidence of SARS-CoV-2 impact on the central nervous system (CNS) raises key questions on its impact for risk of later life cognitive decline, Alzheimer's disease (AD), and other dementia. METHODS: The Alzheimer's Association and representatives from more than 30 countries-with technical guidance from the World Health Organization-have formed an international consortium to study the short-and long-term consequences of SARS-CoV-2 on the CNS-including the underlying biology that may contribute to AD and other dementias. This consortium will link teams from around the world covering more than 22 million COVID-19 cases to enroll two groups of individuals including people with disease, to be evaluated for follow-up evaluations at 6, 9, and 18 months, and people who are already enrolled in existing international research studies to add additional measures and markers of their underlying biology. CONCLUSIONS: The increasing evidence and understanding of SARS-CoV-2's impact on the CNS raises key questions on the impact for risk of later life cognitive decline, AD, and other dementia. This program of studies aims to better understand the long-term consequences that may impact the brain, cognition, and functioning-including the underlying biology that may contribute to AD and other dementias.

Anxiety and depression in adults with autism spectrum disorder: a systematic review and meta-analysis.

Adults with autism spectrum disorder (ASD) are thought to be at disproportionate risk of developing mental health comorbidities, with anxiety and depression being considered most prominent amongst these. Yet, no systematic review has been carried out to date to examine rates of both anxiety and depression focusing specifically on adults with ASD. This systematic review and meta-analysis examined the rates of anxiety and depression in adults with ASD and the impact of factors such as assessment methods and presence of comorbid intellectual disability (ID) diagnosis on estimated prevalence rates. Electronic database searches for studies published between January 2000 and September 2017 identified a total of 35 studies, including 30 studies measuring anxiety (n = 26 070; mean age = 30.9, s.d. = 6.2 years) and 29 studies measuring depression (n = 26 117; mean age = 31.1, s.d. = 6.8 years). The pooled estimation of current and lifetime prevalence for adults with ASD were 27% and 42% for any anxiety disorder, and 23% and 37% for depressive disorder. Further analyses revealed that the use of questionnaire measures and the presence of ID may significantly influence estimates of prevalence. The current literature suffers from a high degree of heterogeneity in study method and an overreliance on clinical samples. These results highlight the importance of community-based studies and the identification and inclusion of well-characterized samples to reduce heterogeneity and bias in estimates of prevalence for comorbidity in adults with ASD and other populations with complex psychiatric presentations.

Changes in health in England, with analysis by English regions and areas of deprivation, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013.

BACKGROUND: In the Global Burden of Disease Study 2013 (GBD 2013), knowledge about health and its determinants has been integrated into a comparable framework to inform health policy. Outputs of this analysis are relevant to current policy questions in England and elsewhere, particularly on health inequalities. We use GBD 2013 data on mortality and causes of death, and disease and injury incidence and prevalence to analyse the burden of disease and injury in England as a whole, in English regions, and within each English region by deprivation quintile. We also assess disease and injury burden in England attributable to potentially preventable risk factors. England and the English regions are compared with the remaining constituent countries of the UK and with comparable countries in the European Union (EU) and beyond. METHODS: We extracted data from the GBD 2013 to compare mortality, causes of death, years of life lost (YLLs), years lived with a disability (YLDs), and disability-adjusted life-years (DALYs) in England, the UK, and 18 other countries (the first 15 EU members [apart from the UK] and Australia, Canada, Norway, and the USA [EU15+]). We extended elements of the analysis to English regions, and subregional areas defined by deprivation quintile (deprivation areas). We used data split by the nine English regions (corresponding to the European boundaries of the Nomenclature for Territorial Statistics level 1 [NUTS 1] regions), and by quintile groups within each English region according to deprivation, thereby making 45 regional deprivation areas. Deprivation quintiles were defined by area of residence ranked at national level by Index of Multiple Deprivation score, 2010. Burden due to various risk factors is described for England using new GBD methodology to estimate independent and overlapping attributable risk for five tiers of behavioural, metabolic, and environmental risk factors. We present results for 306 causes and 2337 sequelae, and 79 risks or risk clusters. FINDINGS: Between 1990 and 2013, life expectancy from birth in England increased by 5·4 years (95% uncertainty interval 5·0-5·8) from 75·9 years (75·9-76·0) to 81·3 years (80·9-81·7); gains were greater for men than for women. Rates of age-standardised YLLs reduced by 41·1% (38·3-43·6), whereas DALYs were reduced by 23·8% (20·9-27·1), and YLDs by 1·4% (0·1-2·8). For these measures, England ranked better than the UK and the EU15+ means. Between 1990 and 2013, the range in life expectancy among 45 regional deprivation areas remained 8·2 years for men and decreased from 7·2 years in 1990 to 6·9 years in 2013 for women. In 2013, the leading cause of YLLs was ischaemic heart disease, and the leading cause of DALYs was low back and neck pain. Known risk factors accounted for 39·6% (37·7-41·7) of DALYs; leading behavioural risk factors were suboptimal diet (10·8% [9·1-12·7]) and tobacco (10·7% [9·4-12·0]). INTERPRETATION: Health in England is improving although substantial opportunities exist for further reductions in the burden of preventable disease. The gap in mortality rates between men and women has reduced, but marked health inequalities between the least deprived and most deprived areas remain. Declines in mortality have not been matched by similar declines in morbidity, resulting in people living longer with diseases. Health policies must therefore address the causes of ill health as well as those of premature mortality. Systematic action locally and nationally is needed to reduce risk exposures, support healthy behaviours, alleviate the severity of chronic disabling disorders, and mitigate the effects of socioeconomic deprivation. FUNDING: Bill & Melinda Gates Foundation and Public Health England.

Epidemiology of autism in adults across age groups and ability levels.

BACKGROUND: The epidemiology of autism in adults has relied on untested projections using childhood research. AIMS: To derive representative estimates of the prevalence of autism and key associations in adults of all ages and ability levels. METHOD: Comparable clinical diagnostic assessments of 7274 Adult Psychiatric Morbidity Survey participants combined with a population case-register survey of 290 adults with intellectual disability. RESULTS: The combined prevalence of autism in adults of all ages in England was 11/1000 (95% CI 3-19/1000). It was higher in those with moderate to profound intellectual disability (odds ratio (OR) = 63.5, 95% CI 27.4-147.2). Male gender was a strong predictor of autism only in those with no or mild intellectual disability (adjusted OR = 8.5, 95% CI 2.0-34.9; interaction with gender, P = 0.03). CONCLUSIONS: Few adults with autism have intellectual disability; however, autism is more prevalent in this population. Autism measures may miss more women with autism.

Prevalence and treatment of common mental disorders in the English national population, 1993-2007.

BACKGROUND: The National Psychiatric Morbidity Surveys include English cross-sectional household samples surveyed in 1993, 2000 and 2007. AIMS: To evaluate frequency of common mental disorders (CMDs), service contact and treatment. METHOD: Common mental disorders were identified with the Clinical Interview Schedule - Revised (CIS-R). Service contact and treatment were established in structured interviews. RESULTS: There were 8615, 6126 and 5385 participants aged 16-64. Prevalence of CMDs was consistent (1993: 14.3%; 2000: 16.0%; 2007: 16.0%), as was past-year primary care physician contact for psychological problems (1993: 11.3%; 2000: 12.0%; 2007: 11.7%). Antidepressant receipt in people with CMDs more than doubled between 1993 (5.7%) and 2000 (14.5%), with little further increase by 2007 (15.9%). Psychological treatments increased in successive surveys. Many with CMDs received no treatment. CONCLUSIONS: Reduction in prevalence did not follow increased treatment uptake, and may require universal public health measures together with individual pharmacological, psychological and computer-based interventions.

Reducing excess mortality due to chronic disease in people with severe mental illness: meta-review of health interventions.

BACKGROUND: People with severe mental illness (SMI) have high rates of chronic disease and premature death. AIMS: To explore the strength of evidence for interventions to reduce risk of mortality in people with SMI. METHOD: In a meta-review of 16 systematic reviews of controlled studies, mortality was the primary outcome (8 reviews). Physiological health measures (body mass index, weight, glucose levels, lipid profiles and blood pressure) were secondary outcomes (14 reviews). RESULTS: Antipsychotic and antidepressant medications had some protective effect on mortality, subject to treatment adherence. Integrative community care programmes may reduce physical morbidity and excess deaths, but the effective ingredients are unknown. Interventions to improve unhealthy lifestyles and risky behaviours can improve risk factor profiles, but longer follow-up is needed. Preventive interventions and improved medical care for comorbid chronic disease may reduce excess mortality, but data are lacking. CONCLUSIONS: Improved adherence to pharmacological and physical health management guidelines is indicated.

Discrimination, domestic violence, abuse, and other adverse life events in people with epilepsy: Population-based study to assess the burden of these events and their contribution to psychopathology.

OBJECTIVE: To quantify the experience of discrimination, domestic violence, abuse, and other stressful life events in people with epilepsy in comparison with the general population and people with other chronic conditions. To assess whether any excess relative burden of these adversities could explain the higher rates of depression in people with epilepsy. METHODS: The Adult Psychiatric Morbidity Survey 2007 used comprehensive interviews with 7,403 individuals living in private residences in England. Doctor-diagnosed epilepsy and other chronic conditions were established by self-report. Discrimination, domestic violence, physical and sexual abuse, and other stressful life events were assessed using computerized self-completion and a face-to-face interview, respectively. RESULTS: People with epilepsy were sevenfold more likely to have reported experiencing discrimination due to health problems (adjusted odds ratio [OR] 7.1; 95% confidence interval [CI] 3.1-16.3), than the general population without epilepsy. This estimate was substantially greater in people with epilepsy than for people with other chronic conditions. People with epilepsy also had greater odds of experiencing domestic violence and sexual abuse than the general population, although these associations were also found in people with other chronic conditions. There was less evidence of an association between epilepsy and a history of physical abuse or having a greater burden of other stressful life events. In exploratory analyses, assuming they lie on the causal pathway, discrimination, domestic violence, and sexual abuse explained 42.7% of the total effect of the relationship between epilepsy and depression or anxiety disorders. SIGNIFICANCE: People with epilepsy can face a range of psychosocial adversities and extensively report feeling discriminated against as compared to the general population. In addition, if confirmed in longitudinal studies, the results suggest that these psychosocial adversities may have a significant role in the development of psychiatric comorbidity and may be targets for future interventions.

UK health performance: findings of the Global Burden of Disease Study 2010.

BACKGROUND: The UK has had universal free health care and public health programmes for more than six decades. Several policy initiatives and structural reforms of the health system have been undertaken. Health expenditure has increased substantially since 1990, albeit from relatively low levels compared with other countries. We used data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2010 (GBD 2010) to examine the patterns of health loss in the UK, the leading preventable risks that explain some of these patterns, and how UK outcomes compare with a set of comparable countries in the European Union and elsewhere in 1990 and 2010. METHODS: We used results of GBD 2010 for 1990 and 2010 for the UK and 18 other comparator nations (the original 15 members of the European Union, Australia, Canada, Norway, and the USA; henceforth EU15+). We present analyses of trends and relative performance for mortality, causes of death, years of life lost (YLLs), years lived with disability (YLDs), disability-adjusted life-years (DALYs), and healthy life expectancy (HALE). We present results for 259 diseases and injuries and for 67 risk factors or clusters of risk factors relevant to the UK. We assessed the UK's rank for age-standardised YLLs and DALYs for their leading causes compared with EU15+ in 1990 and 2010. We estimated 95% uncertainty intervals (UIs) for all measures. FINDINGS: For both mortality and disability, overall health has improved substantially in absolute terms in the UK from 1990 to 2010. Life expectancy in the UK increased by 4·2 years (95% UI 4·2-4·3) from 1990 to 2010. However, the UK performed significantly worse than the EU15+ for age-standardised death rates, age-standardised YLL rates, and life expectancy in 1990, and its relative position had worsened by 2010. Although in most age groups, there have been reductions in age-specific mortality, for men aged 30-34 years, mortality rates have hardly changed (reduction of 3·7%, 95% UI 2·7-4·9). In terms of premature mortality, worsening ranks are most notable for men and women aged 20-54 years. For all age groups, the contributions of Alzheimer's disease (increase of 137%, 16-277), cirrhosis (65%, ?15 to 107), and drug use disorders (577%, 71-942) to premature mortality rose from 1990 to 2010. In 2010, compared with EU15+, the UK had significantly lower rates of age-standardised YLLs for road injury, diabetes, liver cancer, and chronic kidney disease, but significantly greater rates for ischaemic heart disease, chronic obstructive pulmonary disease, lower respiratory infections, breast cancer, other cardiovascular and circulatory disorders, oesophageal cancer, preterm birth complications, congenital anomalies, and aortic aneurysm. Because YLDs per person by age and sex have not changed substantially from 1990 to 2010 but age-specific mortality has been falling, the importance of chronic disability is rising. The major causes of YLDs in 2010 were mental and behavioural disorders (including substance abuse; 21·5% [95 UI 17·2-26·3] of YLDs), and musculoskeletal disorders (30·5% [25·5-35·7]). The leading risk factor in the UK was tobacco (11·8% [10·5-13·3] of DALYs), followed by increased blood pressure (9·0 % [7·5-10·5]), and high body-mass index (8·6% [7·4-9·8]). Diet and physical inactivity accounted for 14·3% (95% UI 12·8-15·9) of UK DALYs in 2010. INTERPRETATION: The performance of the UK in terms of premature mortality is persistently and significantly below the mean of EU15+ and requires additional concerted action. Further progress in premature mortality from several major causes, such as cardiovascular diseases and cancers, will probably require improved public health, prevention, early intervention, and treatment activities. The growing burden of disability, particularly from mental disorders, substance use, musculoskeletal disorders, and falls deserves an integrated and strategic response. FUNDING: Bill & Melinda Gates Foundation.

Common values in assessing health outcomes from disease and injury: disability weights measurement study for the Global Burden of Disease Study 2010.

BACKGROUND: Measurement of the global burden of disease with disability-adjusted life-years (DALYs) requires disability weights that quantify health losses for all non-fatal consequences of disease and injury. There has been extensive debate about a range of conceptual and methodological issues concerning the definition and measurement of these weights. Our primary objective was a comprehensive re-estimation of disability weights for the Global Burden of Disease Study 2010 through a large-scale empirical investigation in which judgments about health losses associated with many causes of disease and injury were elicited from the general public in diverse communities through a new, standardised approach. METHODS: We surveyed respondents in two ways: household surveys of adults aged 18 years or older (face-to-face interviews in Bangladesh, Indonesia, Peru, and Tanzania; telephone interviews in the USA) between Oct 28, 2009, and June 23, 2010; and an open-access web-based survey between July 26, 2010, and May 16, 2011. The surveys used paired comparison questions, in which respondents considered two hypothetical individuals with different, randomly selected health states and indicated which person they regarded as healthier. The web survey added questions about population health equivalence, which compared the overall health benefits of different life-saving or disease-prevention programmes. We analysed paired comparison responses with probit regression analysis on all 220 unique states in the study. We used results from the population health equivalence responses to anchor the results from the paired comparisons on the disability weight scale from 0 (implying no loss of health) to 1 (implying a health loss equivalent to death). Additionally, we compared new disability weights with those used in WHO's most recent update of the Global Burden of Disease Study for 2004. FINDINGS: 13,902 individuals participated in household surveys and 16,328 in the web survey. Analysis of paired comparison responses indicated a high degree of consistency across surveys: correlations between individual survey results and results from analysis of the pooled dataset were 0·9 or higher in all surveys except in Bangladesh (r=0·75). Most of the 220 disability weights were located on the mild end of the severity scale, with 58 (26%) having weights below 0·05. Five (11%) states had weights below 0·01, such as mild anaemia, mild hearing or vision loss, and secondary infertility. The health states with the highest disability weights were acute schizophrenia (0·76) and severe multiple sclerosis (0·71). We identified a broad pattern of agreement between the old and new weights (r=0·70), particularly in the moderate-to-severe range. However, in the mild range below 0·2, many states had significantly lower weights in our study than previously. INTERPRETATION: This study represents the most extensive empirical effort as yet to measure disability weights. By contrast with the popular hypothesis that disability assessments vary widely across samples with different cultural environments, we have reported strong evidence of highly consistent results. FUNDING: Bill & Melinda Gates Foundation.

Gender differences in mental health expectancies in early- and midlife in six European countries.

BACKGROUND: Health expectancies, taking into account both quality and quantity of life, have generally been based on disability and physical functioning. AIMS: To compare mental health expectancies at age 25 and 55 based on common mental disorders both across countries and between males and females. METHOD: Mental health expectancies were calculated by combining mortality data from population life tables and the age-specific prevalence of selected common mental disorders obtained from the European Study of the Epidemiology of Mental Disorders (ESEMeD). RESULTS: For the male population aged 25 (all countries combined) life expectancy was 52 years and life expectancy spent with a common mental disorder was 1.8 years (95% CI 0.7-2.9), 3.4% of overall life expectancy. In comparison, for the female population life expectancy at age 25 was higher (57.9 years) as was life expectancy spent with a common mental disorder (5.1 years, 95% CI 3.6-6.6) and as a proportion of overall life expectancy, 8.8%. By age 55 life expectancy spent with a common mental disorder had reduced to 0.7 years (males) and 2.3 years (females). CONCLUSIONS: Age and gender differences underpin our understanding of years spent with common mental disorders in adulthood. Greater age does not mean living relatively more years with common mental disorder. However, the female population spends more years with common mental disorders and a greater proportion of their longer life expectancy with them (and with each studied separate mental disorder).

Feelings of loneliness among adults with mental disorder.

PURPOSE: Loneliness can affect people at any time and for some it can be an overwhelming feeling leading to negative thoughts and feelings. The current study, based on the Adult Psychiatric Morbidity Survey in England, 2007, quantified the association of loneliness with a range of specific mental disorders and tested whether the relationship was influenced by formal and informal social participation and perceived social support.Methods Using a random probability sample design,7,461 adults were interviewed in a cross-sectional national survey in England in 2007. Common Mental Disorders were assessed using the revised Clinical Interview Schedule;the diagnosis of psychosis was based on the administration of the Schedules of the Clinical Assessment of Neuropsychiatry, while loneliness was derived from an item in the Social Functioning Questionnaire.Results Feelings of loneliness were more prevalent in women (OR = 1.34, 95 % CI 1.20­1.50, P\0.001) as well as in those who were single (OR = 2.24, 95 % C I1.96­2.55, P<0.001), widowed, divorced or separated(OR = 2.78, 95 % CI 2.38­3.23, P<0.001), economically inactive (OR = 1.24, 95 % CI 1.11­1.44,P = 0.007), living in rented accommodation (OR = 1.73,95 % CI 1.53­1.95, P<0.001) or in debt (OR = 2.47,95 % CI 2.07­1.50, P<0.001). Loneliness was associated with all mental disorders, especially depression [corrected].

Methodology and reporting of systematic reviews and meta-analyses of observational studies in psychiatric epidemiology: systematic review.

BACKGROUND: Relatively little is known of the use of systematic review and synthesis methods of non-randomised psychiatric epidemiological studies, which play a vital role in aetiological research, planning and policy-making. AIMS: To evaluate reviews of psychiatric epidemiological studies of functional mental disorders that employed synthesis methods such as systematic review or meta-analysis, or other forms of quantitative review. METHOD: We searched the literature to identify appropriate reviews published during the period 1996 to April 2009. Selected reviews were evaluated using published review guidelines. RESULTS: We found 106 reviews in total, of which 38 (36%) did not mention method of data abstraction from primary studies at all. Many failed to mention study quality, publication bias, bias and confounding. In 73 studies that performed a meta-analysis, 58 (79%) tested for heterogeneity and of these, 47 found significant heterogeneity. Studies that detected heterogeneity made some allowance for this. A major obstacle facing reviewers is the wide variation between primary studies in the use of instruments to measure outcomes and in sampling methods used. CONCLUSIONS: Many deficiencies found in systematic reviews are potentially remediable, although synthesis of primary study findings in a field characterised by so many sources of heterogeneity will remain challenging.

Epilepsy and psychiatric comorbidity: a nationally representative population-based study.

PURPOSE: In a nationally representative population-based study in England, we estimated the burden of psychiatric and neurodevelopmental comorbidities in people with epilepsy. We investigated whether any overrepresentation of comorbidities could be explained by epilepsy being a chronic medical or neurologic condition, or by the confounding effect of demographic and socioeconomic factors or other health conditions. METHODS: The Adult Psychiatric Morbidity Survey 2007 comprised detailed interviews with 7,403 individuals living in private households in England. Doctor-diagnosed epilepsy (and asthma, diabetes, and migraine, chronic conditions for comparison) was ascertained by self-report, and extensive diagnostic and screening interviews were used to assess psychiatric and neurodevelopmental conditions. KEY FINDINGS: The estimated lifetime prevalence of epilepsy in the adult (≥ 16 years old) population of England was 1.2% (95% confidence interval [CI] 1.0-1.5). Almost one-third of the people with epilepsy had an International Classification of Diseases, Tenth Revision (ICD-10) anxiety or depressive disorder (compared with one in six people without epilepsy). Among these, social phobia and agoraphobia, generalized anxiety disorder, depression, and measures of suicidality had strong associations with epilepsy, which remained robust after accounting for potential confounders. These associations were consistently stronger than those in people with asthma or diabetes, and similar to those in people reporting migraine or chronic headaches. Epilepsy was also strongly associated with autism spectrum disorders (odds ratio [OR] 7.4, 95% CI 1.5-35.5) and possible eating disorders, and these associations were not evident in people with asthma, diabetes, or migraine. SIGNIFICANCE: Psychiatric and neurodevelopmental conditions were overrepresented in people with epilepsy. These associations were stronger than with other nonneurologic chronic conditions, and not explained by confounding. Some overlap in the psychopathology observed in epilepsy and migraine cannot rule out the presence of common pathways of psychiatric comorbidity in neurologic conditions. However, associations of epilepsy with conditions such as autism spectrum disorders point to comorbidities specific to epilepsy that may not be shared by other neurologic conditions.

Association of Task-Shared Psychological Interventions With Depression Outcomes in Low- and Middle-Income Countries: A Systematic Review and Individual Patient Data Meta-analysis.

Importance: Task sharing, the training of nonspecialist workers with no formal experience in counseling, is a promising strategy for addressing the large gap in treatment for depression in low- and middle-income countries (LMICs). Objective: To examine the outcomes and moderators of task-shared psychological interventions associated with depression severity, response, and remission. Data Sources: Systematic literature searches in PubMed, Embase, PsycINFO, and Cochrane Library up to January 1, 2021. Study Selection: Randomized clinical trials (RCTs) of task-shared psychological interventions compared with control conditions for adults with depressive symptoms in LMICs were included. Data Extraction and Synthesis: Two researchers independently reviewed the titles, abstracts, and full text of articles from an existing generic meta-analytic database that includes all RCTs on psychotherapy for depression. A systematic review and individual patient data (IPD) meta-analysis was used to estimate the outcomes of task-shared psychological interventions across patient characteristics using mixed-effects models. Procedures for abstracting data and assessing data quality and validity followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline. Main Outcomes and Measures: Primary outcome was reduction in depression symptom severity measured by the 9-item Patient Health Questionnaire (PHQ-9). Response and remission rates were also estimated. Results: Of 13 eligible trials, 11 (4145 participants) contributed IPD. Task-shared psychological interventions were associated with a greater decrease in depressive symptom severity than control conditions (Hedges g, 0.32; 95% CI, -0.26 to -0.38). Participants in the intervention groups had a higher chance of responding (odds ratio, 2.11; 95% CI, 1.60 to 2.80) and remitting (odds ratio, 1.87; 95% CI, 1.20 to 1.99). The presence of psychomotor symptoms was significantly associated with the outcomes of task-shared psychological interventions (ß [SE], -1.21 [0.39]; P = .002). No other significant associations were identified. Heterogeneity among the trials with IPD was 74% (95% CI, 53%-86%). Conclusions and Relevance: In this meta-analysis of IPD, task-shared psychological interventions were associated with a larger reduction in depressive symptom severity and a greater chance of response and remission than control conditions. These findings show potential for the use of task-sharing of psychological interventions across different groups of patients with depression. Further research would help identify which people are most likely to benefit and strengthen larger-scale implementation of this strategy to address the burden of depression in LMICs.

Chronic neuropsychiatric sequelae of SARS-CoV-2: Protocol and methods from the Alzheimer's Association Global Consortium.

Introduction: Coronavirus disease 2019 (COVID-19) has caused >3.5 million deaths worldwide and affected >160 million people. At least twice as many have been infected but remained asymptomatic or minimally symptomatic. COVID-19 includes central nervous system manifestations mediated by inflammation and cerebrovascular, anoxic, and/or viral neurotoxicity mechanisms. More than one third of patients with COVID-19 develop neurologic problems during the acute phase of the illness, including loss of sense of smell or taste, seizures, and stroke. Damage or functional changes to the brain may result in chronic sequelae. The risk of incident cognitive and neuropsychiatric complications appears independent from the severity of the original pulmonary illness. It behooves the scientific and medical community to attempt to understand the molecular and/or systemic factors linking COVID-19 to neurologic illness, both short and long term. Methods: This article describes what is known so far in terms of links among COVID-19, the brain, neurological symptoms, and Alzheimer's disease (AD) and related dementias. We focus on risk factors and possible molecular, inflammatory, and viral mechanisms underlying neurological injury. We also provide a comprehensive description of the Alzheimer's Association Consortium on Chronic Neuropsychiatric Sequelae of SARS-CoV-2 infection (CNS SC2) harmonized methodology to address these questions using a worldwide network of researchers and institutions. Results: Successful harmonization of designs and methods was achieved through a consensus process initially fragmented by specific interest groups (epidemiology, clinical assessments, cognitive evaluation, biomarkers, and neuroimaging). Conclusions from subcommittees were presented to the whole group and discussed extensively. Presently data collection is ongoing at 19 sites in 12 countries representing Asia, Africa, the Americas, and Europe. Discussion: The Alzheimer's Association Global Consortium harmonized methodology is proposed as a model to study long-term neurocognitive sequelae of SARS-CoV-2 infection. Key Points: The following review describes what is known so far in terms of molecular and epidemiological links among COVID-19, the brain, neurological symptoms, and AD and related dementias (ADRD)The primary objective of this large-scale collaboration is to clarify the pathogenesis of ADRD and to advance our understanding of the impact of a neurotropic virus on the long-term risk of cognitive decline and other CNS sequelae. No available evidence supports the notion that cognitive impairment after SARS-CoV-2 infection is a form of dementia (ADRD or otherwise). The longitudinal methodologies espoused by the consortium are intended to provide data to answer this question as clearly as possible controlling for possible confounders. Our specific hypothesis is that SARS-CoV-2 triggers ADRD-like pathology following the extended olfactory cortical network (EOCN) in older individuals with specific genetic susceptibility.The proposed harmonization strategies and flexible study designs offer the possibility to include large samples of under-represented racial and ethnic groups, creating a rich set of harmonized cohorts for future studies of the pathophysiology, determinants, long-term consequences, and trends in cognitive aging, ADRD, and vascular disease.We provide a framework for current and future studies to be carried out within the Consortium. and offers a "green paper" to the research community with a very broad, global base of support, on tools suitable for low- and middle-income countries aimed to compare and combine future longitudinal data on the topic.The Consortium proposes a combination of design and statistical methods as a means of approaching causal inference of the COVID-19 neuropsychiatric sequelae. We expect that deep phenotyping of neuropsychiatric sequelae may provide a series of candidate syndromes with phenomenological and biological characterization that can be further explored. By generating high-quality harmonized data across sites we aim to capture both descriptive and, where possible, causal associations.

Contribution and legacy of John Wing, 1923-2010.

The death of Professor John Wing, one of the giants of 20th-century British and world psychiatry, rightly deserves to be marked by a tribute in the British Journal of Psychiatry. This article has been prepared by four people who knew John personally and through his work, his partner in private and work life, a colleague in Great Britain and one abroad and a pupil, which are set out as four separate contributions. John was born on 22 October 1923. He died on 18 April 2010, aged 87.

Age and birth cohort differences in the prevalence of common mental disorder in England: National Psychiatric Morbidity Surveys 1993-2007.

BACKGROUND: There are concerns that the prevalence of mental disorder is increasing. AIMS: To determine whether the prevalence of common adult mental disorders has increased over time, using age-period-cohort analysis. METHOD: The study consisted of a pseudocohort analysis of a sequence of three cross-sectional surveys of the English household population. The main outcome was common mental disorder, indicated by a score of 12 or above on the Revised Clinical Interview Schedule (CIS-R). Secondary outcomes were neurotic symptoms likely to require treatment, indicated by a CIS-R score of 18 or over, and individual subscale scores for fatigue, sleep problems, irritability and worry. RESULTS: There were 8670 participants in the 1993 survey, 6977 in the 2000 survey and 6815 in the 2007 survey. In men a significant increase in common mental disorder occurred between the cohort born in 1943-9 and that born in 1950-6 (odds ratio 1.4, 95% CI 1.1-1.9) but prevalence in subsequent cohorts remained largely stable. More extended increases in prevalence of sleep problems and mental disorders were observed in women, but not consistently across cohorts or measures. CONCLUSIONS: We found little evidence that the prevalence of common mental disorder is increasing.

Autism spectrum disorder.

Autism spectrum disorder is a construct used to describe individuals with a specific combination of impairments in social communication and repetitive behaviours, highly restricted interests and/or sensory behaviours beginning early in life. The worldwide prevalence of autism is just under 1%, but estimates are higher in high-income countries. Although gross brain pathology is not characteristic of autism, subtle anatomical and functional differences have been observed in post-mortem, neuroimaging and electrophysiological studies. Initially, it was hoped that accurate measurement of behavioural phenotypes would lead to specific genetic subtypes, but genetic findings have mainly applied to heterogeneous groups that are not specific to autism. Psychosocial interventions in children can improve specific behaviours, such as joint attention, language and social engagement, that may affect further development and could reduce symptom severity. However, further research is necessary to identify the long-term needs of people with autism, and treatments and the mechanisms behind them that could result in improved independence and quality of life over time. Families are often the major source of support for people with autism throughout much of life and need to be considered, along with the perspectives of autistic individuals, in both research and practice.

Is it always the same? Variability of depressive symptoms across six European countries.

Using common diagnostic systems together with structured interviews to assess mental disorders has made it possible to compare diagnostic groups of mental disorders across countries. The implicit assumption is that the symptomatology of a particular disorder as defined by the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) will not vary between different countries. However, it is conceivable that there will be some variability in the symptom patterns. The present study examines if differences in depressive symptom patterns across European countries can be found and if there are different associations between symptoms and the latent construct depression. Data from 4025 individuals of the European Study of the Epidemiology of Mental Disorders (ESEMeD) project were analysed. Individuals were interviewed using the Composite International Diagnostic Interview (CIDI 3.0). Confirmatory factor analysis was used to examine the associations between depressive symptoms and the latent construct of depression in each country. The proportions of endorsed symptoms of depression showed only slight variation across European countries and only minor to moderate differences in the associations between depressive symptoms and the latent construct depression. The results demonstrated that in European countries using a fully structured and standardized interview based on European-American diagnostic concepts leads to similar results with regard to depressive symptom patterns.