Feifei Bu’s research while affiliated with University College London and other places

There is a wealth of phenotypic literature on the interplay between mental health and social connections. However, how genetic propensity to mental health traits may be associated with distinct social connections phenotypes (i.e., structural, functional and quality aspects) is largely unexplored. Using polygenic scores (PGSs), we explored the associations between genetic propensity for five mental health traits (PGS-depressive-symptoms, PGS-anxiety, PGS-bipolar-disorder, PGS-schizophrenia, PGS-wellbeing) and four social connection phenotypes (social isolation, loneliness, social support and relationship strain). Linear regressions were conducted in a representative sample of unrelated older adults living in the UK, and analyses were controlled for age, sex, and principal components to account for population stratification. The results show that higher PGS-depressive-symptoms was associated with greater loneliness (B=0.11, CI-95%=0.07, 0.15) and relationship strain (B=0.09, CI-95%=0.05, 0.13) and lower social support (B=-0.07, CI-95%=-0.13, -0.01). Higher PGS-anxiety was associated with higher social isolation (B=0.05, CI-95%=0.00, 0.10) and greater relationship strain (B=0.05, CI-95%=0.01, 0.09). Higher PGS-bipolar-disorder was associated with greater loneliness (B=0.05, CI-95%=0.01, 0.09) and relationship strain (B=0.06, CI-95%=0.02, 0.10). Higher PGS-wellbeing was associated with lower loneliness (B=-0.07, CI-95%=-0.11, -0.03), relationship strain (B=-0.07, CI-95%=-0.11, -0.03), and social isolation (B=-0.07, CI-95%=-0.12, -0.02), and greater social support (B=0.14, CI-95%=0.08, 0.21). This suggests differential associations between different mental health PGSs and distinct aspects of social connections, indicating a nuanced picture. Our findings confirm that genetics play a role in having adequate social connections, which can be supported through social, community, and cultural schemes. They also highlight that genetic confounding is important when using observational data assessing the associations between mental health and social connections.

Background Breathlessness is a common and distressing symptom impacting quality of life and limiting activities of daily living. Social isolation and loneliness are associated with increased morbidity and mortality, and there is an increasing appreciation that these are global health priorities. Qualitative research suggests breathlessness could lead to increased social isolation and loneliness due to limiting participation in social activities and impairing the quality of social interaction. However, research is limited on the relationship of breathlessness with social isolation and loneliness, especially on a population scale. Improving understanding could inform intervention development. Methods Using a nationally representative sample of community dwelling adults aged ≥50years from the English Longitudinal Study of Ageing (N=6260)(44% male), mean(SD) age 70(10) years. We examined associations of breathlessness (MRC breathlessness scale) at baseline, with loneliness (3-item UCLA loneliness scale) and social isolation measured in three ways 1) low social contact (frequency of contact with friends and family); 2) social disengagement (frequency of participation in community organisations, clubs, societies or cultural activities); and 3) domestic isolation (living alone). Data was collected at baseline, and follow-up at 4 and 8 years later, and analysed using ordinary least squares regression. Results At baseline, breathlessness was associated with increased loneliness (p<0.001, coef 0.143), and social isolation, including low social contact (p=0.011, coef 0.084), social disengagement (p<0.001, coef 0.152), and living alone (p=0.019, OR 1.082). Longitudinally, also adjusting for baseline level of the outcome of interest, breathlessness was associated increasing loneliness at 4 (p<0.001, coef 0.111) and 8 (p<0.001, coef 0.134) year follow-up, and with reducing social contact at 4 (p<0.001, coef 0.126) and 8 (p<0.001, coef 0.155) year follow-up. Breathlessness was associated with increasing social disengagement at 8 (0.036, coef 0.075) but not 4 (p=0.303) year follow-up. Change in cohabitation status was not found to be related to breathlessness in our analyses. Findings were independent of all identified confounders. Discussion and Conclusion Breathlessness is related to increasing social isolation and loneliness over time. This may result from breathlessness limiting the amount and quality of social interactions. These findings suggest important psychosocial impacts of breathlessness requiring targeted and holistic management strategies.

over the past decade, ageing clocks have become widely adopted as important tools for understanding biological ageing and have been redefining notions of pro-longevity lifestyles. However, this work is still at an early stage. Some leisure activities, such as arts and cultural engagement (ACEng) have never been studied at all, while others such as physical activity (PA) have only received scant attention. In particular, there is little understanding of whether frequency of engagement or diversity (which provides access to more active ingredients) is more important. This study used 3,354 adults in the UK Household Longitudinal Study - a large, nationally-representative cohort study, which includes six derived epigenetic clocks. We used a doubly robust estimation using the inverse-probability-weighted regression adjustment estimator adjusted for demographic, socioeconomic, behavioural and health covariates, data collection gaps and technical covariates of epigenetic clocks. ACEng and PA were related to slower biological ageing in the PhenoAge and DunedinPoAm clocks, although not to the other measured clocks, with comparable effect sizes between ACEng and PA (Lin, Horvath2018, Horvath2013 and Hannum). For ACEng, diversity and frequency of engagement were related to DunedinPoAm, while for PhenoAge, there was a slightly clearer relationship for frequency than diversity. For PA, higher levels of frequency, diversity, and activeness were related to DunedinPoAm, while only the highest diversity and activeness were related to PhenoAge. These findings were all stronger amongst middle-aged and older adults. This was the first study to show a relationship between ACEng and epigenetic ageing, with comparable effect sizes to PA, suggesting the value of its exploration alongside other lifestyle factors. Decelerations in ageing clocks, including those within our study, have been demonstrated to have clinical (as well as statistical) importance, supporting future exploration as to whether lifestyle changes have any value to slowing or potentially reversing epigenetic ageing.

Background Social prescribing is growing rapidly globally as a way to tackle social determinants of health. However, whom it is reaching and how effectively it is being implemented remains unclear. Aims To gain a comprehensive picture of social prescribing in the UK, from referral routes, reasons, to contacts with link workers and prescribed interventions. Method This study undertook the first analyses of a large database of administrative data from over 160 000 individuals referred to social prescribing across the UK. Data were analysed using descriptive analyses and regression modelling, including logistic regression for binary outcomes and negative binomial regression for count variables. Results Mental health was the most common referral reason and mental health interventions were the most common interventions prescribed. Between 72% and 85% of social prescribing referrals were from medical routes (primary or secondary healthcare). Although these referrals demonstrated equality in reaching across sociodemographic groups, individuals from more deprived areas, younger adults, men, and ethnic minority groups were reached more equitably via non-medical routes (e.g. self-referral, school, charity). Despite 90% of referrals leading to contact with a link worker, only 38% resulted in any intervention being received. A shortage of provision of community activities – especially ones relevant to mental health, practical support and social relationships – was evident. There was also substantial heterogeneity in how social prescribing is implemented across UK nations. Conclusions Mental health is the leading reason for social prescribing referrals, demonstrating its relevance to psychiatrists. But there are inequalities in referrals. Non-medical referral routes could play an important role in addressing inequality in accessing social prescribing and therefore should be prioritised. Additionally, more financial and infrastructural resource and strategic planning are needed to address low intervention rates. Further investment into large-scale data platforms and staff training are needed to continue monitoring the development and distribution of social prescribing.

Increasing evidence links arts engagement with mental health, but the directionality of the link remains unclear. Applying a novel approach to causal inference, we used non-recursive instrumental variable models to analyse two waves of data from the United Kingdom Household Longitudinal Study (N = 17,927). Our findings reveal bidirectional causal relationships between arts engagement (arts participation, cultural attendance, heritage visits) and mental health (GHQ-12 mental distress, SF-12 MCS mental well-being). After adjusting for Time 1 measures and identified confounders, cultural attendance and heritage visits were reciprocally associated with mental distress and mental well-being, while arts participation was only reciprocally associated with mental well-being. The bidirectional effects between arts engagement and mental health are modest but clearly demonstrated not just from mental health to arts but also from arts to mental health. Our findings indicate that previous evidence of an association between arts engagement and mental health is due to bidirectional causal effects. Interventions that boost arts participation, cultural attendance and heritage visits may help break the negative feedback loop and enhance mental health.

Background Social connections have been associated with the risk of several individual chronic conditions, mental health, and biomarkers of health. However, associations between the social connections and multiple long-term conditions (MLTCs) remain unclear. To address this gap, this study aims to assess whether social connections are associated with the number of MLTCs. Methods A cross-sectional study based on core members of wave 2 (2004-2005) of the English Longitudinal Study of Ageing (ELSA) was conducted. MTLCs were measured using a count of 25 self-reported long-term conditions available in ELSA. Social connections included: a summarised measure of perceived social support from children, spouses, friends and other relatives (scores ranging 0-4); summarised in-person contact from children, spouses, friends and other relatives (‘low’, ‘medium’, and ‘high’); and summarised social participation (‘low’, ‘medium’, ‘high'). The outcome distribution fitted a negative binomial curve. Models were adjusted for confounders sequentially. These models were: the crude association; adjustment for age, sex, and ethnicity; further adjustment for wealth quintile and educational attainment; and further adjustment for household composition and labour force status. Multiple imputation was implemented for missing data which occurred across analysis variables. The sensitivity of results was tested against a stricter criterion for counting conditions – a count of the bodily systems affected by MLTCs. All analysis was conducted using Stata v18. Results The analytical sample included 7803 participants with a mean of 2.07 conditions, and variance of 3.12. Whilst controlling for all confounders, social support (IRR=0.81, 95%CI=0.77, 0.85, p<0.001), social contact (high vs. low: IRR=0.94, 95%CI=0.90, 0.99, p<0.026), and social participation (high vs. low: IRR=0.91, 95%CI=0.86, 0.97, p<0.001) were found to associate with the number of MLTCs. These results were not sensitive to the use of a count of the number of bodily systems affected by MLTCs. Conclusion The associations found in this study lend some support to the hypotheses that the presence of social connections may be associated with MLTCs, particularly the presence of social support and social participation. The literature base on this topic is sparce, and by design, this study cannot provide detail on the directionality of findings or whether these associations hold longitudinally. Further research is required to address these limitations and validate the findings here.

Cross-sectional and some longitudinal evidence suggests doing hobbies can reduce substance use, but findings have been inconsistent, and whether associations differ across adolescence remains unclear. This study included 7454 Add Health participants (50% female, 77% White, age mean=14.95 and SD = 1.56). Participants were split into three groups, according to whether they were early (aged 11–14 at baseline), mid (aged 15–16), or late (aged 17–20) adolescents at baseline. The trajectories of binge drinking, marijuana, and tobacco use were analysed in latent growth models across Waves 1–5 (1994–2018). Concurrent associations between substance use and hobby engagement were tested at Waves 1–3 separately in the three age groups. Doing hobbies more frequently was associated with lower odds of binge drinking and marijuana and tobacco use in early adolescence. Although there was initially a similar protective association in mid and late adolescence, this had reversed by Wave 3 for binge drinking and marijuana use, when participants were young adults. This change in the association could be a result of differing social contexts, changes in peer influence, or an indication that creative hobbies are particularly beneficial. It could explain previous inconsistent findings and demonstrates the importance of considering developmental differences when investigating engagement in hobbies.

Population-based proteomics offer a groundbreaking avenue to predict dementia onset. This study employed a proteome-wide, data-driven approach to investigate protein-dementia associations in 229 incident all-cause dementia (ACD) among 3,249 participants from the English Longitudinal Study of Ageing (ELSA) over a median 9.8-year follow-up, then validated in 1,506 incident ACD among 52,745 individuals from the UK Biobank (UKB) over median 13.7 years. NEFL and RPS6KB1 were robustly associated with incident ACD; MMP12 was associated with vascular dementia in ELSA. Additional markers EDA2R and KIM1 (HAVCR1) were identified from sensitivity analyses. Combining NEFL and RPS6KB1 with other factors yielded high predictive accuracy (area under the curve (AUC)=0.871) for incident ACD. Replication in the UKB confirmed associations between identified proteins with various dementia subtypes. Results from reverse Mendelian Randomization also supported the role of several proteins as early dementia biomarkers. These findings underscore proteomics’ potential in identifying novel risk screening targets for dementia.

Background: Social prescribing (SP) is growing rapidly across the world as a way to tackle social determinants of health. However, whom it is reaching and how effectively it is being implemented remains unclear. Methods: This study undertook the first analyses of a large database of administrative data from over 160,000 individuals referred to SP across the UK. Data were analysed using descriptive analyses and regression modelling, including logistic regression for binary outcomes and negative binomial regression for count variables. Findings: 72-85% of referrals for SP were from medical routes (primary or secondary health care). While these referrals demonstrate equality in reaching across socio-demographic groups, individuals from more deprived areas, younger adults, men, and ethnic minority groups were reached more equitably via non-medical referral routes. Despite 90% of referrals leading to contact with a link worker, only 38% resulted in any intervention being received. A shortage of provision of community activities - especially ones relevant to mental health, practical support, and social relationships - was evident. There was also substantial heterogeneity in how SP is being implemented across UK nations. Interpretation: Non-medical referral routes could play an important role in addressing inequality in accessing social prescribing, therefore should be prioritised. Additionally, more financial and infrastructural resource and strategic planning are needed to address low intervention rates. Further investment into large-scale data platforms and staff training are needed to continue monitoring the development and distribution of social prescribing.

Leisure engagement has potential to slow health and functional decline in older age. However, the benefits of different leisure domains for different aspects of aging remains unclear. In 8771 older adults from the Health and Retirement Study (a longitudinal panel study), we measured engagement in physical, creative, cognitive, and community activities. Outcome-wide analyses used 23 aging experiences across seven domains eight years later (daily functioning, physical fitness, long-term physical health problems, heart health, weight, sleep, subjective perceptions of health). Physical activity was related to more positive experiences in all domains but heart health eight years later. Creative engagement was positively related to aging experiences in four domains longitudinally. Cognitive and community engagement were less consistently related to aging experiences. Physical and creative activities may influence important aging metrics, reducing age-related decline and keeping older adults functionally independent for longer, potentially limiting increasing healthcare costs.