Psychosocial factors and hospitalisations for COVID-19: Prospective cohort study based on a community sample.

BACKGROUND: While certain infectious diseases have been linked to socioeconomic disadvantage, mental health problems, and lower cognitive function, relationships with COVID-19 are either uncertain or untested. Our objective was to examine the association of a range of psychosocial factors with hospitalisation for COVID-19. METHODS: UK Biobank, a prospective cohort study, comprises around half a million people who were aged 40-69 years at study induction between 2006 and 2010 when information on psychosocial factors and covariates were captured. Hospitalisations for COVID-19 were ascertained between 16th March and 26th April 2020. RESULTS: There were 908 hospitalisations for COVID-19 in an analytical sample of 431,051 England-based study members. In age- and sex-adjusted analyses, an elevated risk of COVID-19 was related to disadvantaged levels of education (odds ratio; 95% confidence interval: 2.05; 1.70, 2.47), income (2.00; 1.63, 2,47), area deprivation (2.20; 1.86, 2.59), occupation (1.39; 1.14, 1.69), psychological distress (1.58; 1.32, 1.89), mental health (1.50; 1.25, 1.79), neuroticism (1.19; 1.00, 1.42), and performance on two tests of cognitive function - verbal and numerical reasoning (2.66; 2.06, 3.34) and reaction speed (1.27; 1.08, 1.51). These associations were graded (p-value for trend ≤ 0.038) such that effects were apparent across the full psychosocial continua. After mutual adjustment for these characteristics plus ethnicity, comorbidity, and lifestyle factors, only the relationship between lower cognitive function as measured using the reasoning test and risk of the infection remained (1.98; 1.38, 2.85). CONCLUSIONS: A range of psychosocial factors revealed associations with hospitalisation for COVID-19 of which the relation with cognitive function, a marker of health literacy, was most robust.

Does inflammation provide a link between psychosocial work characteristics and diabetes? Analysis of the role of interleukin-6 and C-reactive protein in the Whitehall II cohort study.

OBJECTIVE: Inflammation may underlie the association between psychological stress and cardiometabolic diseases, but this proposition has not been tested longitudinally. We investigated whether the circulating inflammatory markers interleukin-6 (IL-6) and C-reactive protein (CRP) mediate the relationship between psychosocial work characteristics and diabetes. METHODS: We used three phases of data at 5 years intervals from the Whitehall II cohort study, originally recruiting 10,308 civil service employees aged 35-55 years. The data included repeat self-reports of job demands, control and social support, IL-6 from plasma samples, CRP from serum samples, and diabetes, ascertained through oral glucose tolerance test, medications, and self-reports of doctor-diagnosed diabetes. RESULTS: Structural equation models with age, sex and occupational position considering men and women combined, showed that low social support at work, but not high job demands or low job control, was prospectively associated with diabetes (standardized ß  =  0.05, 95% confidence interval (CI) 0.01-0.09) and higher levels of IL-6 (ß  =  0.03, CI 0.00-0.06). The inflammatory markers and diabetes were bidirectionally associated over time. A mediation model including workplace social support, IL-6 and diabetes further showed that 10% of the association between social support and diabetes over the three repeat examinations (total effect ß  =  0.08, CI 0.01-0.15) was attributable to a weak indirect effect through IL-6 (ß  =  0.01, CI 0.00-0.02). A similar indirect effect was observed for CRP in men only, while job control was prospectively associated with IL-6 among women. CONCLUSIONS: This study indicates an association between poor workplace support and diabetes that is partially ascribed to an inflammatory response.

Association of objectively measured physical activity with brain structure: UK Biobank study.

BACKGROUND: Physical activity may be beneficial for cognition but mechanisms are unclear. We examined the association between objectively assessed physical activity and brain volume, with a focus on the hippocampus region. METHODS: We used data from UK Biobank (n = 5272; aged 55.4 ± 7.5 years; 45.6% men) collected through 2013-2016. Participants wore the Axivity AX3 wrist-worn triaxial accelerometer for 7 days to assess habitual physical activity. Structural magnetic resonance imaging was performed using a standard Siemens Skyra 3T running VD13A SP4 to obtain images of the brain. RESULTS: There was an association between physical activity (per SD increase) and grey matter volume after adjustment for a range of covariates, although this association was only detected in older adults (>60 years old). We also observed associations of physical activity with both left (B = 0.52, 95% CI, 0.01, 1.03; P = 0.046) and right hippocampal volume (B = 0.59, 95% CI, 0.08, 1.10; P = 0.024) in covariate-adjusted models. CONCLUSION: In summary, physical activity may play a role in the prevention of neurodegenerative diseases.

History, politics and vulnerability: explaining excess mortality in Scotland and Glasgow.

OBJECTIVES: High levels of excess mortality (i.e. that not explained by deprivation) have been observed for Scotland compared with England & Wales, and especially for Glasgow in comparison with similar post-industrial cities such as Liverpool and Manchester. Many potential explanations have been suggested. Based on an assessment of these, the aim was to develop an understanding of the most likely underlying causes. Note that this paper distils a larger research report, with the aim of reaching wider audiences beyond Scotland, as the important lessons learnt are relevant to other populations. STUDY DESIGN: Review and dialectical synthesis of evidence. METHODS: Forty hypotheses were examined, including those identified from a systematic review. The relevance of each was assessed by means of Bradford Hill's criteria for causality alongside-for hypotheses deemed causally linked to mortality-comparisons of exposures between Glasgow and Liverpool/Manchester, and between Scotland and the rest of Great Britain. Where gaps in the evidence base were identified, new research was undertaken. Causal chains of relevant hypotheses were created, each tested in terms of its ability to explain the many different aspects of excess mortality. The models were further tested with key informants from public health and other disciplines. RESULTS: In Glasgow's case, the city was made more vulnerable to important socioeconomic (deprivation, deindustrialisation) and political (detrimental economic and social policies) exposures, resulting in worse outcomes. This vulnerability was generated by a series of historical factors, processes and decisions: the lagged effects of historical overcrowding; post-war regional policy including the socially selective relocation of population to outside the city; more detrimental processes of urban change which impacted on living conditions; and differences in local government responses to UK government policy in the 1980s which both impacted in negative terms in Glasgow and also conferred protective effects on comparator cities. Further resulting protective factors were identified (e.g. greater 'social capital' in Liverpool) which placed Glasgow at a further relative disadvantage. Other contributory factors were highlighted, including the inadequate measurement of deprivation. A similar 'explanatory model' resulted for Scotland as a whole. This included: the components of the Glasgow model, given their impact on nationally measured outcomes; inadequate measurement of deprivation; the lagged effects of deprivation (in particular higher levels of overcrowding historically); and additional key vulnerabilities. CONCLUSIONS: The work has helped to further understanding of the underlying causes of Glasgow's and Scotland's high levels of excess mortality. The implications for policy include the need to address three issues simultaneously: to protect against key exposures (e.g. poverty) which impact detrimentally across all parts of the UK; to address the existing consequences of Glasgow's and Scotland's vulnerability; and to mitigate against the effects of future vulnerabilities which are likely to emerge from policy responses to contemporary problems which fail sufficiently to consider and to prevent long-term, unintended social consequences.

Intelligence and neuroticism in relation to depression and psychological distress: Evidence from two large population cohorts.

BACKGROUND: Neuroticism is a risk factor for selected mental and physical illnesses and is inversely associated with intelligence. Intelligence appears to interact with neuroticism and mitigate its detrimental effects on physical health and mortality. However, the inter-relationships of neuroticism and intelligence for major depressive disorder (MDD) and psychological distress has not been well examined. METHODS: Associations and interactions between neuroticism and general intelligence (g) on MDD, self-reported depression, and psychological distress were examined in two population-based cohorts: Generation Scotland: Scottish Family Health Study (GS:SFHS, n=19,200) and UK Biobank (n=90,529). The Eysenck Personality Scale Short Form-Revised measured neuroticism and g was extracted from multiple cognitive ability tests in each cohort. Family structure was adjusted for in GS:SFHS. RESULTS: Neuroticism was strongly associated with increased risk for depression and higher psychological distress in both samples. Although intelligence conferred no consistent independent effects on depression, it did increase the risk for depression across samples once neuroticism was adjusted for. Results suggest that higher intelligence may ameliorate the association between neuroticism and self-reported depression although no significant interaction was found for clinical MDD. Intelligence was inversely associated with psychological distress across cohorts. A small interaction was found across samples such that lower psychological distress associates with higher intelligence and lower neuroticism, although effect sizes were small. CONCLUSIONS: From two large cohort studies, our findings suggest intelligence acts a protective factor in mitigating the effects of neuroticism on psychological distress. Intelligence does not confer protection against diagnosis of depression in those high in neuroticism.

Job strain as a risk factor for clinical depression: systematic review and meta-analysis with additional individual participant data.

BACKGROUND: Adverse psychosocial working environments characterized by job strain (the combination of high demands and low control at work) are associated with an increased risk of depressive symptoms among employees, but evidence on clinically diagnosed depression is scarce. We examined job strain as a risk factor for clinical depression. METHOD: We identified published cohort studies from a systematic literature search in PubMed and PsycNET and obtained 14 cohort studies with unpublished individual-level data from the Individual-Participant-Data Meta-analysis in Working Populations (IPD-Work) Consortium. Summary estimates of the association were obtained using random-effects models. Individual-level data analyses were based on a pre-published study protocol. RESULTS: We included six published studies with a total of 27 461 individuals and 914 incident cases of clinical depression. From unpublished datasets we included 120 221 individuals and 982 first episodes of hospital-treated clinical depression. Job strain was associated with an increased risk of clinical depression in both published [relative risk (RR) = 1.77, 95% confidence interval (CI) 1.47-2.13] and unpublished datasets (RR = 1.27, 95% CI 1.04-1.55). Further individual participant analyses showed a similar association across sociodemographic subgroups and after excluding individuals with baseline somatic disease. The association was unchanged when excluding individuals with baseline depressive symptoms (RR = 1.25, 95% CI 0.94-1.65), but attenuated on adjustment for a continuous depressive symptoms score (RR = 1.03, 95% CI 0.81-1.32). CONCLUSIONS: Job strain may precipitate clinical depression among employees. Future intervention studies should test whether job strain is a modifiable risk factor for depression.

Insulin-like growth factor 1 and risk of depression in older people: the English Longitudinal Study of Ageing.

Depressive disorders are a leading cause of disability in older age. Although the role of psychosocial and behavioural predictors has been well examined, little is known about the biological origins of depression. Findings from animal studies have implicated insulin-like growth factor 1 (IGF-1) in the aetiology of this disorder. A total of 6017 older adults (mean age of 65.7 years; 55% women) from the English Longitudinal Study of Ageing provided serum levels of IGF-1 (mean=15.9 nmol l(-1), s.d. 5.7) during a nurse visit in 2008. Depression symptoms were assessed in the same year and again in 2012 using the eight-item Center for Epidemiologic Studies Depression Scale. Self-reports of a physician-diagnosis of depression were also collected at both time points. In separate analyses for men and women, the results from both the cross-sectional and longitudinal analyses revealed a 'U'-shaped pattern of association, such that lower and higher levels of IGF-1 were associated with a slightly elevated risk of depression, whereas the lowest risk was seen around the median levels. Thus, in men, with the lowest quintile of IGF-1 as the referent, the age-adjusted odds ratios (95% confidence interval) of developing depression symptoms after 4 years of follow-up, for increasing quintiles of IGF-1, were: 0.51 (0.28-0.91), 0.50 (0.27-0.92), 0.63 (0.35-1.15) and 0.63 (0.35-1.13) (P-value for quadratic association 0.002). Some attenuation of these effects was apparent after adjustment for co-morbidity, socioeconomic status and health behaviours. In conclusion, in the present study of older adults, there was some evidence that moderate levels of IGF-1 levels conferred a reduced risk of depression.

Depressive symptoms and obesity: instrumental variable analysis using mother-offspring pairs in the 1970 British Cohort Study.

BACKGROUND: The extent to which depression and obesity are causally related remains to be determined. We used intergenerational data on mother-offspring pairs in an instrumental variable analysis to examine the longitudinal association between adolescent depressive symptoms and body mass index (BMI) in adulthood. METHODS: A total of 4733 mother-offspring pairs were identified from the 1970 British Cohort Study. Mothers completed the Malaise Inventory to assess depressive symptoms on three occasions across their offsprings' childhood/adolescence (aged 5, 10 and 16 years). Height and weight were recorded in mother and offspring (aged 16 years). Measures of height, weight and the Malaise Inventory were repeated in the participant at the age of 42 years. RESULTS: Maternal malaise score was associated with offspring malaise score, thus confirming the validity of the chosen instrumental variable. A higher mother's malaise score was associated with higher offspring BMI at follow-up (B=0.043; 95% confidence interval (CI): 0.013, 0.072). There was a higher risk of adulthood offspring obesity in mothers with two or three episodes of depression compared with one or none (odds ratio, 1.42; 95% CI: 1.14, 1.76). The maternal malaise-offspring BMI association remained (P=0.003) after adjustment for offspring malaise score, suggesting that maternal mental health influences offspring obesity through mechanisms other than depression. Results from standard and instrumental variable analyses did not support a causal pathway in a direction from BMI to depression. CONCLUSIONS: Our data support a causal pathway linking adolescent depressive symptoms to adiposity in adulthood over 26 years follow-up. The reverse direction, that is, adiposity to depression, was not supported.

Sarcopenic obesity and risk of new onset depressive symptoms in older adults: English Longitudinal Study of Ageing.

BACKGROUND: We examined the role of sarcopenic obesity as a risk factor for new-onset depressive symptoms over 6-year follow-up in a large sample of older adults. METHODS: The sample comprised 3862 community dwelling participants (1779 men, 2083 women; mean age 64.6±8.3 years) without depressive symptoms at baseline, recruited from the English Longitudinal Study of Ageing. At baseline and 4-year follow-up, handgrip strength (kg) of the dominant hand was assessed using a hand-held dynamometer, as a measure of sarcopenia. The outcome was new onset depressive symptoms at 6-year follow-up, defined as a score of ⩾4 on the 8-item Centre of Epidemiological Studies Depression scale. Sarcopenic obesity was defined as obese individuals (body mass index ⩾30 kg m(-)(2)) in the lowest tertile of sex-specific grip strength (<35.3 kg men; <19.6 kg women). RESULTS: Using a multivariable logistic regression model, the risk of depressive symptoms was greatest in obese adults in the lowest tertile of handgrip strength (odds ratio (OR), 1.79, 95% confidence interval (CI), 1.10, 2.89) compared with non-obese individuals with high handgrip strength. Participants who were obese at baseline and had a decrease of more than 1 s.d. in grip strength over 4-year follow-up were at greatest risk of depressive symptoms (OR=1.97, 95% CI, 1.22, 3.17) compared with non-obese with stable grip strength. CONCLUSIONS: A reduction in grip strength was associated with higher risk of depressive symptoms in obese participants only, suggesting that sarcopenic obesity is a risk factor for depressive symptoms.

Severity of depressive symptoms as a predictor of mortality: the English longitudinal study of ageing.

BACKGROUND: Major depressive disorder and subthreshold depression have been associated with premature mortality. We investigated the association between depressive symptoms and mortality across the full continuum of severity. METHOD: We used Cox proportional hazards models to examine the association between depressive symptom severity, assessed using the eight-item Center for Epidemiological Studies Depression Scale (CES-D; range 0-8), and the risk of all-cause mortality over a 9-year follow-up, in 11 104 members of the English Longitudinal Study of Ageing. RESULTS: During follow-up, one fifth of study members died (N = 2267). Depressive symptoms were associated with increased mortality across the full range of severity (p trend < 0.001). Relative to study members with no symptoms, an increased risk of mortality was found in people with depressive symptoms of a low [hazard ratio (HR) for a score of 2 was 1.59, 95% confidence interval (CI) 1.40-1.82], moderate (score of 4: HR 1.80, 95% CI 1.52-2.13) and high (score of 8: HR 2.27, 95% CI 1.69-3.04) severity, suggesting risk emerges at low levels but plateaus thereafter. A third of participants (36.4%, 95% CI 35.5-37.3) reported depressive symptoms associated with an increased mortality risk. Adjustment for physical activity, physical illnesses, and impairments in physical and cognitive functioning attenuated this association (p trend = 0.25). CONCLUSIONS: Depressive symptoms are associated with an increased mortality risk even at low levels of symptom severity. This association is explained by physical activity, physical illnesses, and impairments in physical and cognitive functioning.

Interleukin-6 as a predictor of symptom resolution in psychological distress: a cohort study.

BACKGROUND: Elevated levels of interleukin-6 (IL-6) have been associated with the development of common mental disorders, such as depression, but its role in symptom resolution is unclear. METHOD: We examined the association between IL-6 and symptom resolution in a non-clinical sample of participants with psychological distress. RESULTS: Relative to high IL-6 levels, low levels at baseline were associated with symptom resolution at follow-up [age- and sex-adjusted risk ratio (RR) = 1.15, 95% confidence interval (CI) 1.06-1.25]. Further adjustment for covariates had little effect on the association. Symptomatic participants with repeated low IL-6 were more likely to be symptom-free at follow-up compared with those with repeated high IL-6 (RR = 1.21, 95% CI 1.03-1.41). Among the symptomatic participants with elevated IL-6 at baseline, IL-6 decreased along with symptom resolution. CONCLUSIONS: IL-6 is potentially related to the mechanisms underlying recovery from symptoms of mental ill health. Further studies are needed to examine these mechanisms and to confirm the findings in relation to clinical depression.

Job strain and the risk of severe asthma exacerbations: a meta-analysis of individual-participant data from 100 000 European men and women.

BACKGROUND: Many patients and healthcare professionals believe that work-related psychosocial stress, such as job strain, can make asthma worse, but this is not corroborated by empirical evidence. We investigated the associations between job strain and the incidence of severe asthma exacerbations in working-age European men and women. METHODS: We analysed individual-level data, collected between 1985 and 2010, from 102 175 working-age men and women in 11 prospective European studies. Job strain (a combination of high demands and low control at work) was self-reported at baseline. Incident severe asthma exacerbations were ascertained from national hospitalization and death registries. Associations between job strain and asthma exacerbations were modelled using Cox regression and the study-specific findings combined using random-effects meta-analyses. RESULTS: During a median follow-up of 10 years, 1 109 individuals experienced a severe asthma exacerbation (430 with asthma as the primary diagnostic code). In the age- and sex-adjusted analyses, job strain was associated with an increased risk of severe asthma exacerbations defined using the primary diagnostic code (hazard ratio, HR: 1.27, 95% confidence interval, CI: 1.00, 1.61). This association attenuated towards the null after adjustment for potential confounders (HR: 1.22, 95% CI: 0.96, 1.55). No association was observed in the analyses with asthma defined using any diagnostic code (HR: 1.01, 95% CI: 0.86, 1.19). CONCLUSIONS: Our findings suggest that job strain is probably not an important risk factor for severe asthma exacerbations leading to hospitalization or death.

Is personality associated with cancer incidence and mortality? An individual-participant meta-analysis of 2156 incident cancer cases among 42,843 men and women.

BACKGROUND: The putative role of personality in cancer risk has been controversial, and the evidence remains inconclusive. METHODS: We pooled data from six prospective cohort studies (British Household Panel Survey; Health and Retirement Study; Household, Income, and Labour Dynamics in Australia; Midlife in the United Survey; Wisconsin Longitudinal Study Graduate; and Sibling samples) for an individual-participant meta-analysis to examine whether personality traits of the Five Factor Model (extraversion, neuroticism, agreeableness, conscientiousness, and openness to experience) were associated with the incidence of cancer and cancer mortality in 42,843 cancer-free men and women at baseline (mean age 52.2 years, 55.6% women). RESULTS: During an average follow-up of 5.4 years, there were 2156 incident cancer cases. In random-effects meta-analysis adjusted for age, sex, and race/ethnicity, none of the personality traits were associated with the incidence of all cancers or any of the six site-specific cancers included in the analysis (lung, colon, breast, prostate, skin, and leukaemia/lymphoma). In the three cohorts with cause-specific mortality data (421 cancer deaths among 21,835 participants), none of the personality traits were associated with cancer mortality. CONCLUSIONS: These data suggest that personality is not associated with increased risk of incident cancer or cancer-related mortality.

Association of metabolically healthy obesity with depressive symptoms: pooled analysis of eight studies.

The hypothesis of metabolically healthy obesity posits that adverse health effects of obesity are largely avoided when obesity is accompanied by a favorable metabolic profile. We tested this hypothesis with depressive symptoms as the outcome using cross-sectional data on obesity, metabolic health and depressive symptoms. Data were extracted from eight studies and pooled for individual-participant meta-analysis with 30,337 men and women aged 15-105 years (mean age=46.1). Clinic measures included height, weight and metabolic risk factors (high blood pressure, high triglycerides, low high-density lipoprotein cholesterol, high C-reactive protein and high glycated hemoglobin). Depressive symptoms were assessed using clinical interview or standardized rating scales. The pooled sample comprised 7673 (25%) obese participants (body mass index ⩾30 kg m(-2)). Compared to all non-obese individuals, the OR for depressive symptoms was higher in metabolically unhealthy obese individuals with two or more metabolic risk factors (1.45; 95% confidence interval (CI)=1.30, 1.61) and for metabolically healthy obese with ⩽1 metabolic risk factor (1.19; 95% CI=1.03, 1.37), adjusted for sex, age and race/ethnicity. Metabolically unhealthy obesity was associated with higher depression risk (OR=1.23; 95% CI=1.05, 1.45) compared with metabolically healthy obesity. These associations were consistent across studies with no evidence for heterogeneity in estimates (all I(2)-values<4%). In conclusion, obese persons with a favorable metabolic profile have a slightly increased risk of depressive symptoms compared with non-obese, but the risk is greater when obesity is combined with an adverse metabolic profile. These findings suggest that metabolically healthy obesity is not a completely benign condition in relation to depression risk.

Physical activity patterns over 10 years in relation to body mass index and waist circumference: the Whitehall II cohort study.

OBJECTIVE: Physical activity patterns over 10-years in relation to changes in body mass index (BMI) and waist circumference (WC) were examined. DESIGN AND METHODS: Participants (4,880, mean age 49.3 years at baseline) from the Whitehall II cohort study were included. Self-reported physical activity and anthropometric data were collected at baseline (1991) and twice during follow-up (1997 and 2002). RESULTS: At baseline, meeting established guidelines for physical activity, particularly through vigorous activity, was associated with lower WC (multivariable adjusted B compared to not meeting the guidelines -2.08 cm, 95% CI, -1.39, -0.75) and BMI (-0.34 kg/m(2) , -0.10, -0.59). Based on repeat data, "high adherence" to the guidelines compared to "rare adherence" over follow-up was associated with lower BMI (adjusted difference, -0.43 kg/m(2) , 95% CI, -0.79, -0.08) and WC (-2.50 cm, 95% CI, -3.46, -1.54) at follow-up. Compared to participants that remained stable between 1997 and 2002 (change of <2.5 h/week), those that reported an increase in moderate-vigorous physical activity of at least 2.5 h/week displayed lower BMI (-0.40 kg/m(2) , 95% CI, -0.71, -0.08) and WC (-1.10 cm, 95% CI, -1.95, -0.75). CONCLUSION: Regular physical activity, confirmed by repeated assessments, is associated with relatively favorable levels of adiposity markers after 10 years follow-up.

Ageing and the prevalence and treatment of mental health problems.

BACKGROUND: Ageing is an important factor in the development of mental health problems and their treatment. We assessed age trajectories of common mental disorders (CMDs) and psychotherapy utilization from adolescence to old age, and examined whether these trajectories were modified by time period or birth cohort effects. METHOD: British Household Panel Survey (BHPS) with an 18-year follow-up between 1991 and 2009 (n=30 224 participants, aged 15­100 years, with an average 7.3 person-observations per person). CMDs were assessed with the 12-item version of the General Health Questionnaire (GHQ). Psychotherapy treatment utilization during the past year was self-reported by the participants. The modifying influences of time period and cohort effects were assessed in a cohort-sequential longitudinal setting. RESULTS: Following a moderate decrease after age 50, the prevalence of GHQ caseness increased steeply from age 75. This increase was more marked in the 2000s (GHQ prevalence increasing from 24% to 43%) than in the 1990s (from 22% to 34%). Psychotherapy utilization decreased after age 55, with no time period or cohort effects modifying the age trajectory. These ageing patterns were replicated in within-individual longitudinal analysis. CONCLUSIONS: Old age is associated with higher risk of CMDs, and this association has become more marked during the past two decades. Ageing is also associated with an increasing discrepancy between prevalence of mental disorders and provision of treatment, as indicated by lower use of psychotherapy in older individuals.