Key Points Question How has the mental health of the UK population changed from before to during the COVID-19 pandemic? Findings This cohort study of 49 993 participants in 11 longitudinal studies found that mental health has deteriorated from before the start of the COVID-19 pandemic, and this deterioration was sustained across the first year of the pandemic. Deterioration in mental health varied by sociodemographic factors, namely age, sex, and education, and did not recover when social restrictions were eased. Meaning The substantial deterioration in mental health during the ongoing COVID-19 pandemic observed in this study highlights the need for improved mental health care provision and broader support to minimize the risk of longer-term mental health consequences and widening health inequalities.
Background Depression is a disabling and highly prevalent condition where genetic and epigenetic, such as DNA methylation (DNAm), differences contribute to disease risk. DNA methylation is influenced by genetic variation but the association between polygenic risk of depression and DNA methylation is unknown. Methods We investigated the association between polygenic risk scores (PRS) for depression and DNAm by conducting a methylome-wide association study (MWAS) in Generation Scotland (N = 8898, mean age = 49.8 years) with replication in the Lothian Birth Cohorts of 1921 and 1936 and adults in the Avon Longitudinal Study of Parents and Children (ALSPAC) (Ncombined = 2049, mean age = 79.1, 69.6 and 47.2 years, respectively). We also conducted a replication MWAS in the ALSPAC children (N = 423, mean age = 17.1 years). Gene ontology analysis was conducted for the cytosine-guanine dinucleotide (CpG) probes significantly associated with depression PRS, followed by Mendelian randomisation (MR) analysis to infer the causal relationship between depression and DNAm. Results Widespread associations (NCpG = 71, pBonferroni < 0.05, p < 6.3 × 10−8) were found between PRS constructed using genetic risk variants for depression and DNAm in CpG probes that localised to genes involved in immune responses and neural development. The effect sizes for the significant associations were highly correlated between the discovery and replication samples in adults (r = 0.79) and in adolescents (r = 0.82). Gene Ontology analysis showed that significant CpG probes are enriched in immunological processes in the human leukocyte antigen system. Additional MWAS was conducted for each lead genetic risk variant. Over 47.9% of the independent genetic risk variants included in the PRS showed associations with DNAm in CpG probes located in both the same (cis) and distal (trans) locations to the genetic loci (pBonferroni < 0.045). Subsequent MR analysis showed that there are a greater number of causal effects found from DNAm to depression than vice versa (DNAm to depression: pFDR ranged from 0.024 to 7.45 × 10−30; depression to DNAm: pFDR ranged from 0.028 to 0.003). Conclusions PRS for depression, especially those constructed from genome-wide significant genetic risk variants, showed methylome-wide differences associated with immune responses. Findings from MR analysis provided evidence for causal effect of DNAm to depression.
Background Young adults and especially those with pre-existing mental health conditions, such as disordered eating and self-harm, appear to be at greater risk of developing metal health problems during the COVID-19 pandemic. However, it is unclear whether this increased risk is affected by any changes in lockdown restrictions, and whether any lifestyle changes could moderate this increased risk. Methods In a longitudinal UK-based birth cohort (The Avon Longitudinal Study of Parents and Children, ALSPAC) we assessed the relationship between pre-pandemic measures of disordered eating and self-harm and mental health during the COVID-19 pandemic in 2657 young adults. Regression models examined the relationship between self-reported disordered eating, self-harm, and both disordered eating and self-harm at age 25 years and depressive symptoms, anxiety symptoms and mental wellbeing during a period of eased restrictions in the COVID-19 pandemic (May–July 2020) when participants were aged 27–29 years. Analyses were adjusted for sex, questionnaire completion date, pre-pandemic socioeconomic disadvantage and pre-pandemic mental health and wellbeing. We also examined whether lifestyle changes (sleep, exercise, alcohol, visiting green space, eating, talking with family/friends, hobbies, relaxation) in the initial UK lockdown (April–May 2020) moderated these associations. Results Pre-existing disordered eating, self-harm and comorbid disordered eating and self-harm were all associated with the reporting of a higher frequency of depressive symptoms and anxiety symptoms, and poorer mental wellbeing during the pandemic compared to individuals without disordered eating and self-harm. Associations remained when adjusting for pre-pandemic mental health measures. There was little evidence that interactions between disordered eating and self-harm exposures and lifestyle change moderators affected pandemic mental health and wellbeing. Conclusions Young adults with pre-pandemic disordered eating, self-harm and comorbid disordered eating and self-harm were at increased risk for developing symptoms of depression, anxiety and poor mental wellbeing during the COVID-19 pandemic, even when accounting for pre-pandemic mental health. Lifestyle changes during the pandemic do not appear to alter this risk. A greater focus on rapid and responsive service provision is essential to reduce the impact of the pandemic on the mental health of these already vulnerable individuals. Plain English summary The aim of this project was to explore the mental health of young adults with disordered eating behaviours (such as fasting, vomiting/taking laxatives, binge-eating and excessive exercise) and self-harm during the COVID-19 pandemic. We analysed data from an established study that has followed children from birth (in 1991 and 1992) up to present day, including during the pandemic when participants were 28 years old. We looked at the relationship between disordered eating and/or self-harm behaviours from before the pandemic and mental health problems (symptoms of depression and anxiety) and mental wellbeing during the pandemic. We also explored whether there were any lifestyle changes (such as changes in sleep, exercise, visiting green space) that might be linked to better mental health and wellbeing in young adults with disordered eating and self-harm. We found that young adults with prior disordered eating and/or self-harm had more symptoms of depression and anxiety, and worse mental wellbeing than individuals without prior disordered eating or self-harm. However, lifestyle changes did not appear to affect mental health and wellbeing in these young adults. Our findings suggest that people with a history of disordered eating and/or self-harm were at high risk for developing mental health problems during the pandemic, and they will need help from mental health services.
Background: SARS-CoV-2 antibody levels can be used to assess humoral immune responses following SARS-CoV-2 infection or vaccination, and may predict risk of future infection. Higher levels of SARS-CoV-2 anti-Spike antibodies are known to be associated with increased protection against future SARS-CoV-2 infection. However, variation in antibody levels and risk factors for lower antibody levels following each round of SARS-CoV-2 vaccination have not been explored across a wide range of socio-demographic, SARS-CoV-2 infection and vaccination, and health factors within population-based cohorts. Methods: Samples were collected from 9,361 individuals from TwinsUK and ALSPAC UK population-based longitudinal studies and tested for SARS-CoV-2 antibodies. Cross-sectional sampling was undertaken jointly in April-May 2021 (TwinsUK, N = 4,256; ALSPAC, N = 4,622), and in TwinsUK only in November 2021-January 2022 (N = 3,575). Variation in antibody levels after first, second, and third SARS-CoV-2 vaccination with health, socio-demographic, SARS-CoV-2 infection and SARS-CoV-2 vaccination variables were analysed. Using multivariable logistic regression models, we tested associations between antibody levels following vaccination and: (1) SARS-CoV-2 infection following vaccination(s); (2) health, socio-demographic, SARS-CoV-2 infection and SARS-CoV-2 vaccination variables. Results: Within TwinsUK, single-vaccinated individuals with the lowest 20% of anti-Spike antibody levels at initial testing had 3-fold greater odds of SARS-CoV-2 infection over the next six to nine months (OR = 2.9, 95% CI: 1.4, 6.0), compared to the top 20%. In TwinsUK and ALSPAC, individuals identified as at increased risk of COVID-19 complication through the UK 'Shielded Patient List' had consistently greater odds (2- to 4-fold) of having antibody levels in the lowest 10%. Third vaccination increased absolute antibody levels for almost all individuals, and reduced relative disparities compared with earlier vaccinations. Conclusions: These findings quantify the association between antibody level and risk of subsequent infection, and support a policy of triple vaccination for the generation of protective antibodies. Funding: Antibody testing was funded by UK Health Security Agency. The National Core Studies program is funded by COVID-19 Longitudinal Health and Wellbeing - National Core Study (LHW-NCS) HMT/UKRI/MRC (MC_PC_20030 & MC_PC_20059). Related funding was also provided by the NIHR 606 (CONVALESCENCE grant COV-LT-0009). TwinsUK is funded by the Wellcome Trust, Medical Research Council, Versus Arthritis, European Union Horizon 2020, Chronic Disease Research Foundation (CDRF), Zoe Ltd and the National Institute for Health Research (NIHR) Clinical Research Network (CRN) and Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust in partnership with King's College London. The UK Medical Research Council and Wellcome (Grant ref: 217065/Z/19/Z) and the University of Bristol provide core support for ALSPAC.
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