Search

Environmental exposures during the perinatal period are known to have a long-term effect on adult physical and mental health. One such influential environmental exposure is the time of year of birth which affects the amount of daylight, nutrients, and viral load that an individual is exposed to within this key developmental period. Here, we investigate associations between season of birth (seasonality), four mental health traits (n = 137,588) and multi-modal neuroimaging measures (n = 33,212) within the UK Biobank. Summer births were associated with probable recurrent Major Depressive Disorder (β = 0.026, pcorr= 0.028) and greater mean cortical thickness in temporal and occipital lobes (β = 0.013 to 0.014, pcorr<0.05). Winter births were associated with greater white matter integrity globally, in the association fibers, thalamic radiations, and six individual tracts (β = -0.013 to -0.022, pcorr<0.05). Results of sensitivity analyses adjusting for birth weight were similar, with an additional association between winter birth and white matter microstructure in the forceps minor and between summer births, greater cingulate thickness and amygdala volume. Further analyses revealed associations between probable depressive phenotypes and a range of neuroimaging measures but a paucity of interactions with seasonality. Our results suggest that seasonality of birth may affect later-life brain structure and play a role in lifetime recurrent Major Depressive Disorder. Due to the small effect sizes observed, and the lack of associations with other mental health traits, further research is required to validate birth season effects in the context of different latitudes, and by co-examining genetic and epigenetic measures to reveal informative biological pathways. [ABSTRACT FROM AUTHOR]

This article outlines a novel conceptual framework to examine English society's ruling institutions. Usually called 'The Establishment', the term has been a thorn in the side of analyses of class, status and power in British sociology as it stands between polemic and an explanation for England's peculiar exaggeration of status over class. Drawing upon Lévi-Strauss's concept of a 'house-society', the article rethinks how England's ruling institutions are called upon to do two things at once: disguise political-economic interests through the language of kinship and naturalise status and belonging. English society's ruling institutions are overdetermined in the call to create legitimate and exclusive membership to something, perhaps anachronistically, called ' Great Britain'. Tracing this to the origins of English class nomenclature in early modern political thought, the article applies this framework to a discussion of Eton College and the Etonians' relationship to our present political crisis. [ABSTRACT FROM AUTHOR]

Background: Metabolite profiling of blood by nuclear magnetic resonance (NMR) is invaluable to clinical biomarker discovery. To ensure robustness, biomarkers require validation in large cohorts and across multiple centres. However, collection procedures are known to impact on the stability of biofluids that may, in turn, degrade biomarker signals. We trialled three blood collection tubes with the aim of solving technical challenges due to preanalytical variation in blood metabolite levels that are common in cohort studies. Methods: We first investigated global NMR-based metabolite variability between biobanks, including the large-scale UK Biobank and TwinsUK biobank of the general UK population, and more targeted biobanks derived from multicentre clinical trials relating to inflammatory bowel disease. We then compared the blood metabolome of 12 healthy adult volunteers when collected into either sodium fluoride/potassium oxalate, lithium heparin, or serum blood tubes using different pre-processing parameters. Results: Preanalytical variation in the method of blood collection strongly influences metabolite composition within and between biobanks. This variability can largely be attributed to glucose and lactate. In the healthy control cohort, the fluoride oxalate collection tube prevented fluctuation in glucose and lactate levels for 24 hours at either 4 °C or room temperature (20 °C). Conclusions: Blood collection into a fluoride oxalate collection tube appears to preserve the blood metabolome with delayed processing up to 24 hours at 4 °C. This method may be considered as an alternative when rapid processing is not feasible. [ABSTRACT FROM AUTHOR]

Early in the nineteenth century, members in the UK Parliament (MPs) hardly ever debated education. When they did, it was nearly always in the context of aid for the religious instruction of the poor. Indeed, even by 1850, nearly two decades after the first Great Reform Act (1832), the Prime Minister Lord John Russell made the case that a system of compulsory state schooling would be immoral and un-British. Yet, by the '80s, MPs debating in Westminster routinely drew connections between schooling and the most critical social issues of the day: social-class mobility and equity, child welfare, national development, emigration, and the civil service, among others. What explains the expanding, and expansive, political uses that elite policymakers put to schooling? How did schooling and education take on such an aggrandized role in society for British statesmen? To address these questions, this paper combines natural language processing techniques, semantic network, discourse, and regression analyses to read and interpret the ∼1.1 million political speeches given in the UK Houses of Parliament during the long nineteenth century (1804–1913). In contrast to explanations emphasizing the direct role that economic, social, and political development as well as conflict played in the UK state's historic expansion, this piece demonstrates how social scientization, the sweeping international epistemic movement that institutionalized and diffused functionalist social theory, created the context that made it possible for political elites to see and promote schooling as an effective policy instrument of greater cultural rationalization supporting the development of capitalist industrial society. [ABSTRACT FROM AUTHOR]

Key Points: Questions: Are hypothesized associations between familial risk of depression and lower cognitive performance evident across the life span for both family history and genetic risk measures? Findings: In this cohort study including 57 308 participants from 4 cohorts, among the 3 younger cohorts (age range, 6 to 42 years), family history of depression was primarily associated with lower performance in the memory domain, whereas in the older cohort (age range, 44 to 83 years), the associations were shown for processing speed, attention, and executive function. Associations were similar in the polygenic risk score analyses and were evident even in participants who had never been depressed themselves but had a family history of depression. Meaning: In this study, whether assessed by family history or genetic data, depression in prior generations was associated with lower cognitive performance in offspring, which has important implications for understanding and addressing potentially modifiable risk factors. This cohort study evaluates associations between familial risk of depression and cognitive performance in 4 independent cohorts with varied depth of assessment, using both family history and genetic risk measures. Importance: Cognitive impairment in depression is poorly understood. Family history of depression is a potentially useful risk marker for cognitive impairment, facilitating early identification and targeted intervention in those at highest risk, even if they do not themselves have depression. Several research cohorts have emerged recently that enable findings to be compared according to varying depths of family history phenotyping, in some cases also with genetic data, across the life span. Objective: To investigate associations between familial risk of depression and cognitive performance in 4 independent cohorts with varied depth of assessment, using both family history and genetic risk measures. Design, Setting, and Participants: This study used data from the Three Generations at High and Low Risk of Depression Followed Longitudinally (TGS) family study (data collected from 1982 to 2015) and 3 large population cohorts, including the Adolescent Brain Cognitive Development (ABCD) study (data collected from 2016 to 2021), National Longitudinal Study of Adolescent to Adult Health (Add Health; data collected from 1994 to 2018), and UK Biobank (data collected from 2006 to 2022). Children and adults with or without familial risk of depression were included. Cross-sectional analyses were conducted from March to June 2022. Exposures: Family history (across 1 or 2 prior generations) and polygenic risk of depression. Main Outcomes and Measures: Neurocognitive tests at follow-up. Regression models were adjusted for confounders and corrected for multiple comparisons. Results: A total of 57 308 participants were studied, including 87 from TGS (42 [48%] female; mean [SD] age, 19.7 [6.6] years), 10 258 from ABCD (4899 [48%] female; mean [SD] age, 12.0 [0.7] years), 1064 from Add Health (584 [49%] female; mean [SD] age, 37.8 [1.9] years), and 45 899 from UK Biobank (23 605 [51%] female; mean [SD] age, 64.0 [7.7] years). In the younger cohorts (TGS, ABCD, and Add Health), family history of depression was primarily associated with lower performance in the memory domain, and there were indications that this may be partly associated with educational and socioeconomic factors. In the older UK Biobank cohort, there were associations with processing speed, attention, and executive function, with little evidence of education or socioeconomic influences. These associations were evident even in participants who had never been depressed themselves. Effect sizes between familial risk of depression and neurocognitive test performance were largest in TGS; the largest standardized mean differences in primary analyses were −0.55 (95% CI, −1.49 to 0.38) in TGS, −0.09 (95% CI, −0.15 to −0.03) in ABCD, −0.16 (95% CI, −0.31 to −0.01) in Add Health, and −0.10 (95% CI, −0.13 to −0.06) in UK Biobank. Results were generally similar in the polygenic risk score analyses. In UK Biobank, several tasks showed statistically significant associations in the polygenic risk score analysis that were not evident in the family history models. Conclusions and Relevance: In this study, whether assessed by family history or genetic data, depression in prior generations was associated with lower cognitive performance in offspring. There are opportunities to generate hypotheses about how this arises through genetic and environmental determinants, moderators of brain development and brain aging, and potentially modifiable social and lifestyle factors across the life span. [ABSTRACT FROM AUTHOR]

Background: Widening participation (WP) for underrepresented students through six-year gateway courses helps to widen the demographic representation of doctors in the UK. 'Most students from gateway courses graduate, even though many enter with lower grades than standard entry medicine students.' This study aims to compare the graduate outcomes of gateway and SEM cohorts from the same universities. Methods: Data from 2007–13 from the UK Medical Education Database (UKMED) were available for graduates of gateway and SEM courses at three UK medical schools. Outcome measures were passing an entry exam on the first attempt, Annual Review of Competency Progression (ARCP) outcome and being offered a level one training position from the first application. The univariate analysis compared the two groups. Logistic regressions, predicting outcomes by course type, controlled for attainment on completion of medical school. Results: Four thousand four hundred forty-five doctors were included in the analysis. There was no difference found in the ARCP outcome between gateway and SEM graduates. Gateway graduates were less likely to pass their first attempt at any membership exam than graduates of SEM courses (39% vs 63%). Gateway graduates were less likely to be offered a level 1 training position on their first application (75% vs 82%). Graduates of gateway courses were more likely to apply to General Practitioner (GP) training programmes than SEM graduates (56% vs 39%). Conclusions: Gateway courses increase the diversity of backgrounds represented within the profession and importantly the number of applications to GP training. However, differences in cohort performance are shown to continue to exist in the postgraduate arena and further research is required to ascertain the reasons for this. [ABSTRACT FROM AUTHOR]

Background Non-random selection of analytic subsamples could introduce selection bias in observational studies. We explored the potential presence and impact of selection in studies of SARS-CoV-2 infection and COVID-19 prognosis. Methods We tested the association of a broad range of characteristics with selection into COVID-19 analytic subsamples in the Avon Longitudinal Study of Parents and Children (ALSPAC) and UK Biobank (UKB). We then conducted empirical analyses and simulations to explore the potential presence, direction and magnitude of bias due to this selection (relative to our defined UK-based adult target populations) when estimating the association of body mass index (BMI) with SARS-CoV-2 infection and death-with-COVID-19. Results In both cohorts, a broad range of characteristics was related to selection, sometimes in opposite directions (e.g. more-educated people were more likely to have data on SARS-CoV-2 infection in ALSPAC, but less likely in UKB). Higher BMI was associated with higher odds of SARS-CoV-2 infection and death-with-COVID-19. We found non-negligible bias in many simulated scenarios. Conclusions Analyses using COVID-19 self-reported or national registry data may be biased due to selection. The magnitude and direction of this bias depend on the outcome definition, the true effect of the risk factor and the assumed selection mechanism; these are likely to differ between studies with different target populations. Bias due to sample selection is a key concern in COVID-19 research based on national registry data, especially as countries end free mass testing. The framework we have used can be applied by other researchers assessing the extent to which their results may be biased for their research question of interest. [ABSTRACT FROM AUTHOR]

Background: There is uncertainty whether unipolar mania is a discrete sub‐type of bipolar disorder. Disrupted rest/activity rhythms are a key feature of bipolar disorder (BD) but have not been well characterised in unipolar mania/hypomania (UM). We compared subjective and objective rest/activity patterns, demographic and mental health outcomes across BD, UM and control groups. Methods: UK residents aged 37–73 years were recruited into UK Biobank from 2006 to 2010. BD, UM and control groups were identified via a mental health questionnaire. Demographic, mental health and subjective sleep outcomes were self‐reported. Accelerometery data were available for a subset of participants, and objective measures of sleep and activity were derived. Results: A greater proportion of males met UM criteria, and more females were in the BD group. Both BD and UM groups had poor mental health outcomes vs. controls. Objectively measured activity differed between all three groups: UM had highest levels of activity and BD lowest. The UM group had shorter sleep duration compared to controls. Subjective rest/activity measures showed that both mood disorder groups (compared to controls) had later chronotype preference, more disturbed sleep and increased difficulty getting up in the morning. However, the UM group were more likely to report an early chronotype compared to BD and control groups. Conclusions: BD and UM share features in common, but key differences support the proposition that UM may be a distinct and more clinically homogenous disorder. UM was characterised by a higher proportion of males, early chronotype, increased activity and shorter sleep duration. [ABSTRACT FROM AUTHOR]

The history of British and French society over the long nineteenth century can be framed as two contrasting histories of bureaucratization. In France, a "rational" body of organizational rules and procedures coalesced quickly around the state, taking their paradigmatic form during the First Republic and Empire (1792-1814) but stagnating thereafter. In Britain, these structures developed piecemeal, and over a longer time, gaining relative coherence by the midcentury. In both cases, however, office work became a major social, ideological, and cultural phenomenon, one that warranted literary portrayal despite its apparent unconduciveness to conventional narrative forms. In this article I illustrate the shifting character of "office novels" within these contexts, and I accordingly operate from both a comparative and a longitudinal perspective: comparing novels from France and Britain produced during the midcentury period (pivotal in the history of bureaucracy and of the novel) that focus on office life. I argue that the changing role of the office career between William Makepeace Thackeray's abortive office Bildungsroman The History of Samuel Titmarsh (1841) and Anthony Trollope's The Three Clerks (1858) reflects the reform, saturation, and ideological legitimation of bureaucratic forms in Britain over this period. Meanwhile, the transition from Honor'e de Balzac's highly reflexive satirical novel Les Employ'es (1844) to E' mile Gaboriau's office-hopping Picaresque Les Gens de Bureau (1862) reflects an increasing jadedness in France about the ability of these structures to change. [ABSTRACT FROM AUTHOR]

Introduction: Situational judgement tests (SJTs) have been widely adopted, internationally, into medical selection. It was hoped that such assessments could identify candidates likely to exhibit future professional behaviours. Understanding how performance on such tests may predict the risk of disciplinary action during medical school would provide evidence for the validity of such SJTs within student selection. It would also inform the implementation of such tests within student recruitment. Methods: This cohort study used data for 6910 medical students from 36 UK medical schools who sat the University Clinical Aptitude Test (UCAT) SJT in 2013. The relationship between SJT scores at application and the risk of subsequent disciplinary action during their studies was modelled. The incremental ability of the SJT scores to predict the risk of disciplinary action, above that already provided by UCAT cognitive test scores and secondary (high) school achievement, was also evaluated in 5535 of the students with information available on this latter metric. Results: Two hundred and ten (3.05%) of the students in the cohort experienced disciplinary action. The risk of disciplinary action reduced with increasing performance on the admissions SJT (odds ratio (OR) 0.80, 95% confidence interval (CI) 0.69 to 0.92, p = 0.002). This effect remained similar after adjusting for cognitive performance and prior academic attainment (OR 0.77, 95% CI 0.65 to 0.92, p = 0.004). The overall estimated effect‐size was small (Cohen's d = 0.08) and no evidence of 'threshold' effects were observed for the SJT scores and risk of disciplinary action. Conclusions: Performance on admissions SJTs can, at least modestly, incrementally predict the risk of subsequent disciplinary action, supporting their use in this context. However, for this SJT and outcome, there did not seem a distinct threshold score above which the risk of disciplinary action disproportionately increased. This should be considered when using the scores within medical selection. Performance on an admissions Situational Judgment Test is reported to predict risk of formal disciplinary action in medical students with implications for how such tests should be used to improve medical professionalism. [ABSTRACT FROM AUTHOR]

Traditional accounts of state expansion and of the rise of state schooling in the nineteenth century emphasize economic, political, and social development as well as conflict and domination. These accounts explain the introduction of new state structures, like ministries of education, rules of compulsion, and the general elaboration of bureaucracies. This article contributes to the historical sociological study of state expansion with specific regard to schooling by refocusing on the role that macrocultural processes of social scientization played in shaping the discursive construction and expansion of the state. Designed to analyze the 1.3 million speeches given in the UK parliament during the nineteenth century, the research reported here supports the argument that the development, professionalization, and institutionalization of the social sciences—social scientization—was a powerful force of cultural construction across the West and was positively associated with expanded notions of the state, as evidenced with the case of the United Kingdom. This article therefore not only provides an important alternative view to those who emphasize economic and social transformation but it also advances the empirical study of the powerful role that social science, as generative institution of cultural construction, played in shaping official discourses of the state—in this instance, the schooling state. [ABSTRACT FROM AUTHOR]

Recent research suggests genetic variation in the Klotho locus may modify the association between APOE ɛ4 and cognitive impairment. We tested for associations and interactions between these genotypes versus risk of dementia, cognitive abilities, and brain structure in older UK Biobank participants. Klotho status was indexed with rs9536314 heterozygosity (versus not), in unrelated people with versus without APOE ɛ4 genotype, corrected for various confounders. APOE ɛ4 associated with increased risk of dementia, worse cognitive abilities, and brain structure. Klotho was associated with better reasoning. There were no interactions; potentially suggesting an age- and pathology-dependent Klotho effect. [ABSTRACT FROM AUTHOR]

Background: Treatment Resistant Bipolar Depression (TRBD) is a major contributor to the burden of disease associated with Bipolar Disorder (BD). Treatment options for people experiencing bipolar depression are limited to three interventions listed by National Institute for Health and Care: lamotrigine, quetiapine and olanzapine, of which the latter two are often not well tolerated. The majority of depressed people with BD are therefore prescribed antidepressants despite limited efficacy. This demonstrates an unmet need for additional interventions. Pramipexole has been shown to improve mood symptoms in animal models of depression, in people with Parkinson's Disease and two proof of principle trials of pramipexole for people with BD who are currently depressed. Methods: The PAX-BD study, funded by the United Kingdom (UK) National Institute for Health Research, aims to extend previous findings by assessing the efficacy, safety and health economic impact of pramipexole in addition to mood stabilisers for patients with TRBD. A randomised, double-blind, placebo controlled design is conducted in a naturalistic UK National Health Service setting. An internal pilot study to examine feasibility and acceptability of the study design is included. Participants with TRBD are screened from National Health Service secondary care services in up to 40 mental health trusts in the UK, with the aim of recruiting approximately 414 participants into a pre-randomisation phase to achieve a target of 290 randomised participants. Primary safety and efficacy measures are at 12 weeks following randomisation, with follow up of participants to 52 weeks. The primary outcome is depressive symptoms as measured by Quick Inventory for Depressive Symptomatology – Self Report. Secondary outcomes include changes in anxiety, manic symptoms, tolerability, acceptability, quality of life and cost-effectiveness. Outcome measures are collected remotely using self-report tools implemented online, and observer-rated assessments conducted via telephone. ANCOVA will be used to examine the difference in rating scale scores between treatment arms, and dependent on compliance in completion of weekly self-report measures. A mixed effects linear regression model may also be used to account for repeated measures. Trial registration: ISRCTN72151939. Registered on 28 August 2019, http://www.isrctn.com/ISRCTN72151939 Protocol Version: 04-FEB-2021, Version 9.0. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 pandemic and mitigation measures are likely to have a marked effect on mental health. It is important to use longitudinal data to improve inferences.Aims: To quantify the prevalence of depression, anxiety and mental well-being before and during the COVID-19 pandemic. Also, to identify groups at risk of depression and/or anxiety during the pandemic.Method: Data were from the Avon Longitudinal Study of Parents and Children (ALSPAC) index generation (n = 2850, mean age 28 years) and parent generation (n = 3720, mean age 59 years), and Generation Scotland (n = 4233, mean age 59 years). Depression was measured with the Short Mood and Feelings Questionnaire in ALSPAC and the Patient Health Questionnaire-9 in Generation Scotland. Anxiety and mental well-being were measured with the Generalised Anxiety Disorder Assessment-7 and the Short Warwick Edinburgh Mental Wellbeing Scale.Results: Depression during the pandemic was similar to pre-pandemic levels in the ALSPAC index generation, but those experiencing anxiety had almost doubled, at 24% (95% CI 23-26%) compared with a pre-pandemic level of 13% (95% CI 12-14%). In both studies, anxiety and depression during the pandemic was greater in younger members, women, those with pre-existing mental/physical health conditions and individuals in socioeconomic adversity, even when controlling for pre-pandemic anxiety and depression.Conclusions: These results provide evidence for increased anxiety in young people that is coincident with the pandemic. Specific groups are at elevated risk of depression and anxiety during the COVID-19 pandemic. This is important for planning current mental health provisions and for long-term impact beyond this pandemic. [ABSTRACT FROM AUTHOR]

Chronic pain is highly prevalent worldwide and imparts a significant socioeconomic and public health burden. Factors influencing susceptibility to, and mechanisms of, chronic pain development, are not fully understood, but sex is thought to play a significant role, and chronic pain is more prevalent in women than in men. To investigate sex differences in chronic pain, we carried out a sex-stratified genome-wide association study of Multisite Chronic Pain (MCP), a derived chronic pain phenotype, in UK Biobank on 178,556 men and 209,093 women, as well as investigating sex-specific genetic correlations with a range of psychiatric, autoimmune and anthropometric phenotypes and the relationship between sex-specific polygenic risk scores for MCP and chronic widespread pain. We also assessed whether MCP-associated genes showed expression pattern enrichment across tissues. A total of 123 SNPs at five independent loci were significantly associated with MCP in men. In women, a total of 286 genome-wide significant SNPs at ten independent loci were discovered. Meta-analysis of sex-stratified GWAS outputs revealed a further 87 independent associated SNPs. Gene-level analyses revealed sex-specific MCP associations, with 31 genes significantly associated in females, 37 genes associated in males, and a single gene, DCC, associated in both sexes. We found evidence for sex-specific pleiotropy and risk for MCP was found to be associated with chronic widespread pain in a sex-differential manner. Male and female MCP were highly genetically correlated, but at an rg of significantly less than 1 (0.92). All 37 male MCP-associated genes and all but one of 31 female MCP-associated genes were found to be expressed in the dorsal root ganglion, and there was a degree of enrichment for expression in sex-specific tissues. Overall, the findings indicate that sex differences in chronic pain exist at the SNP, gene and transcript abundance level, and highlight possible sex-specific pleiotropy for MCP. Results support the proposition of a strong central nervous-system component to chronic pain in both sexes, additionally highlighting a potential role for the DRG and nociception. Author summary: Chronic pain is a highly prevalent and debilitating condition, which is more common in women than in men. Sex differences in this condition may be a result of several factors, including differences between the sexes in genetic variation related to chronic pain and gene expression differences related to sex. To explore sex differences in chronic pain from a genetic perspective, we looked for genetic variants associated with chronic pain in men and women separately in a large general-population cohort, and compared the variants we identified between the sexes. We assessed the degree of overlap between genetic variants associated with chronic pain in each sex and those associated with a wide range of other traits, including major depression, body-mass index and suicidality. We also investigated gene expression patterns across a range of tissues for genes associated with chronic pain in each sex, in particular examining expression in neural and non-neural human and mouse tissues and assessing the degree of Dorsal Root Ganglion (DRG) enrichment, an important peripheral nervous system component involved in chronic pain. This work contributes to understanding of chronic pain as a trait and of sex differences in chronic pain at the levels of genetics and gene expression. [ABSTRACT FROM AUTHOR]

Whilst previous observational studies have linked negative thought processes such as an external locus of control and holding negative cognitive styles with depression, the directionality of these associations and the potential role that these factors play in the transition to adulthood and parenthood has not yet been investigated. This study examined the association between locus of control and negative cognitive styles in adolescence and probable depression in young adulthood and whether parenthood moderated these associations. Using a UK prospective population-based birth cohort study: the Avon Longitudinal Study of Parents and Children (ALSPAC), we examined the association between external locus of control and negative cognitive styles in adolescence with odds of depression in 4,301 young adults using logistic regression models unadjusted and adjusted for potential confounding factors. Interaction terms were employed to examine whether parenthood (i.e., having become a parent or not) moderated these associations. Over 20% of young adults in our sample were at or above the clinical threshold indicating probable depression. For each standard deviation (SD) increase in external locus of control in adolescence, there was a 19% (95% CI: 8–32%) higher odds of having probable depression in young adulthood, after adjusting for various confounding factors including baseline mood and different demographic and life events variables. Similarly, for each SD increase in negative cognitive styles in adolescence, there was a 29% (95% CI: 16–44%) higher odds of having probable depression in the adjusted model. We found little evidence that parenthood status moderated the relationship between external locus of control or negative cognitive styles in adolescence and probable depression following adjustment for confounding factors. Effect estimates were comparable when performed in the complete case dataset. These findings suggest that having an external locus of control and holding negative cognitive styles in mid- to late adolescence is associated with an increased likelihood of probable depression in young adulthood. [ABSTRACT FROM AUTHOR]

Levels of activity are often affected in psychiatric disorders and can be core symptoms of illness. Advances in technology now allow the accurate assessment of activity levels but it remains unclear whether alterations in activity arise from shared risk factors for developing psychiatric disorders, such as genetics, or are better explained as consequences of the disorders and their associated factors. We aimed to examine objectively-measured physical activity in individuals with psychiatric disorders, and assess the role of genetic liability for psychiatric disorders on physical activity. Accelerometer data were available on 95,529 UK Biobank participants, including measures of overall mean activity and minutes per day of moderate activity, walking, sedentary activity, and sleep. Linear regressions measured associations between psychiatric diagnosis and activity levels, and polygenic risk scores (PRS) for psychiatric disorders and activity levels. Genetic correlations were calculated between psychiatric disorders and different types of activity. Having a diagnosis of schizophrenia, bipolar disorder, depression, or autism spectrum disorders (ASD) was associated with reduced overall activity compared to unaffected controls. In individuals without a psychiatric disorder, reduced overall activity levels were associated with PRS for schizophrenia, depression, and ASD. ADHD PRS was associated with increased overall activity. Genetic correlations were consistent with PRS findings. Variation in physical activity is an important feature across psychiatric disorders. Whilst levels of activity are associated with genetic liability to psychiatric disorders to a very limited extent, the substantial differences in activity levels in those with psychiatric disorders most likely arise as a consequences of disorder-related factors. [ABSTRACT FROM AUTHOR]

Background. Systemic inflammation has been linked with mood disorder and cognitive impairment. The extent of this relationship remains uncertain, with the effects of serum inflammatory biomarkers compared to genetic predisposition toward inflammation yet to be clearly established. Methods. We investigated the magnitude of associations between C-reactive protein (CRP) measures, lifetime history of bipolar disorder or major depression, and cognitive function (reaction time and visuospatial memory) in 84,268UKBiobank participants. CRP was measured in serum and a polygenic risk score for CRP was calculated, based on a published genome-wide association study. Multiple regression models adjusted for sociodemographic and clinical confounders. Results. Increased serum CRP was significantly associated with mood disorder history (Kruskal-Wallis H = 196.06, p <0.001, X² =0.002) but increased polygenic risk for CRP was not (F =0.668, p =0.648, X² < 0.001). Compared to the lowest quintile, the highest serum CRP quintile was significantly associated with both negative and positive differences in cognitive performance (fully adjusted models: reaction time B =-0.030, 95% CI=-0.052, -0.008; visuospatial memory B = 0.066, 95% CI= 0.042, 0.089). More severe mood disorder categories were significantly associated with worse cognitive performance and this was not moderated by serum or genetic CRP level. Conclusions. In this large cohort study, we found that measured inflammation was associated with mood disorder history, but genetic predisposition to inflammation was not. The association between mood disorder and worse cognitive performance was very small and did not vary by CRP level. The inconsistent relationship between CRP measures and cognitive performance warrants further study. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) is a neurodegenerative condition where the underlying etiology is still unclear. Investigating the potential influence of apolipoprotein E (APOE), a major genetic risk factor, on common blood biomarkers could provide a greater understanding of the mechanisms of AD and dementia risk.Objective: Our objective was to conduct the largest (to date) single-protocol investigation of blood biomarkers in the context of APOE genotype, in UK Biobank.Methods: After quality control and exclusions, data on 395,769 participants of White European ancestry were available for analysis. Linear regressions were used to test potential associations between APOE genotypes and biomarkers.Results: Several biomarkers significantly associated with APOEɛ4 'risk' and ɛ2 'protective' genotypes (versus neutral ɛ3/ɛ3). Most associations supported previous data: for example, ɛ4 genotype was associated with elevated low-density lipoprotein cholesterol (LDL) (standardized beta [b] = 0.150 standard deviations [SDs] per allele, p < 0.001) and ɛ2 with lower LDL (b = -0.456 SDs, p < 0.001). There were however instances of associations found in unexpected directions: e.g., ɛ4 and increased insulin-like growth factor (IGF-1) (b = 0.017, p < 0.001) where lower levels have been previously suggested as an AD risk factor.Conclusion: These findings highlight biomarker differences in non-demented people at genetic risk for dementia. The evidence herein supports previous hypotheses of involvement from cardiometabolic and neuroinflammatory pathways. [ABSTRACT FROM AUTHOR]

Background: Medical schools differ, particularly in their teaching, but it is unclear whether such differences matter, although influential claims are often made. The Medical School Differences (MedDifs) study brings together a wide range of measures of UK medical schools, including postgraduate performance, fitness to practise issues, specialty choice, preparedness, satisfaction, teaching styles, entry criteria and institutional factors.Method: Aggregated data were collected for 50 measures across 29 UK medical schools. Data include institutional history (e.g. rate of production of hospital and GP specialists in the past), curricular influences (e.g. PBL schools, spend per student, staff-student ratio), selection measures (e.g. entry grades), teaching and assessment (e.g. traditional vs PBL, specialty teaching, self-regulated learning), student satisfaction, Foundation selection scores, Foundation satisfaction, postgraduate examination performance and fitness to practise (postgraduate progression, GMC sanctions). Six specialties (General Practice, Psychiatry, Anaesthetics, Obstetrics and Gynaecology, Internal Medicine, Surgery) were examined in more detail.Results: Medical school differences are stable across time (median alpha = 0.835). The 50 measures were highly correlated, 395 (32.2%) of 1225 correlations being significant with p < 0.05, and 201 (16.4%) reached a Tukey-adjusted criterion of p < 0.0025. Problem-based learning (PBL) schools differ on many measures, including lower performance on postgraduate assessments. While these are in part explained by lower entry grades, a surprising finding is that schools such as PBL schools which reported greater student satisfaction with feedback also showed lower performance at postgraduate examinations. More medical school teaching of psychiatry, surgery and anaesthetics did not result in more specialist trainees. Schools that taught more general practice did have more graduates entering GP training, but those graduates performed less well in MRCGP examinations, the negative correlation resulting from numbers of GP trainees and exam outcomes being affected both by non-traditional teaching and by greater historical production of GPs. Postgraduate exam outcomes were also higher in schools with more self-regulated learning, but lower in larger medical schools. A path model for 29 measures found a complex causal nexus, most measures causing or being caused by other measures. Postgraduate exam performance was influenced by earlier attainment, at entry to Foundation and entry to medical school (the so-called academic backbone), and by self-regulated learning. Foundation measures of satisfaction, including preparedness, had no subsequent influence on outcomes. Fitness to practise issues were more frequent in schools producing more male graduates and more GPs.Conclusions: Medical schools differ in large numbers of ways that are causally interconnected. Differences between schools in postgraduate examination performance, training problems and GMC sanctions have important implications for the quality of patient care and patient safety. [ABSTRACT FROM AUTHOR]

Objective: To assess the cross-sectional and prospective associations between depressive symptoms, neuroticism, and participation in breast and cervical screening in the UK.Methods: Women in the UK Biobank cohort with complete data who were eligible for breast cancer screening (aged 50-70 years, N = 143 461) and/or cervical screening (<65 years, N = 141 753) at baseline recruitment (2006-2010) and those with follow-up data (2014-2019) were identified (N = 11 050 and N = 9780 for breast and cervical screening). Depressive symptoms and neuroticism were self-reported at baseline (range 0-12 with higher scores reflecting greater severity). Primary outcomes were reporting being up to date with breast and cervical screening. For prospective analyses, patterns of screening participation from baseline to follow-up were identified. Logistic regression was used to analyse associations, adjusted for potential confounding factors.Results: More severe depressive symptoms were associated with reduced likelihood of breast (OR = 0.960, 95% CI: 0.950,0.970) and cervical (OR = 0.958, 95% CI: 0.950,0.966) screening participation, in cross-sectional analyses. Higher neuroticism scores were associated with reduced cervical screening participation, but the opposite was found for breast cancer screening. Examination of individual neuroticism items revealed that anxiety and worry were associated with increased breast screening. At follow-up, higher baseline depressive symptoms were related to decreased cervical screening (OR = 0.955, 95% CI: 0.913,0.999), but not with breast screening.Conclusions: More severe depressive symptoms may be a barrier for breast and cervical screening and could be an indicator for more proactive strategies to improve uptake. [ABSTRACT FROM AUTHOR]

Background: Gateway courses are increasingly popular widening participation routes into medicine. These six year courses provide a more accessible entry route into medical school and aim to support under-represented students' progress and graduation as doctors. There is little evidence on the performance of gateway students and this study compares attainment and aptitude on entry, and outcomes at graduation of students on the UK's three longest running gateway courses with students studying on a standard entry medical degree (SEMED) course at the same institutions. Methods: Data were obtained from the UK Medical Education Database for students starting between 2007 and 2012 at three UK institutions. These data included A-levels and Universities Clinical Aptitude Test scores on entry to medical school and the Educational Performance Measure (EPM) decile, Situational Judgement Test (SJT) and Prescribing Safety Assessment (PSA) scores as outcomes measures. Multiple regression models were used to test for difference in outcomes between the two types of course, controlling for attainment and aptitude on entry. Results: Four thounsand three hundred forty students were included in the analysis, 560 on gateway courses and 3785 on SEMED courses. Students on SEMED courses had higher attainment (Cohen's d = 1.338) and aptitude (Cohen's d = 1.078) on entry. On exit SEMED students had higher EPM scores (Cohen's d = 0.616) and PSA scores (Cohen's d = 0.653). When accounting for attainment and aptitude on entry course type is still a significant predictor of EPM and PSA, but the proportion of the variation in outcome explained by course type drops from 6.4 to 1.6% for EPM Decile and from 5.3% to less than 1% for the PSA score. There is a smaller significant difference in SJT scores, with SEMED having higher scores (Cohen's d = 0.114). However, when measures of performance on entry are accounted for, course type is no longer a significant predictor of SJT scores. Conclusions: This study shows the differences of the available measures between gateway students and SEMED students on entry to their medical degrees are greater than the differences on exit. This provides modest evidence that gateway courses allow students from under-represented groups to achieve greater academic potential. [ABSTRACT FROM AUTHOR]

Background: There is strong evidence that people born in winter and in spring have a small increased risk of schizophrenia. As this 'season of birth' effect underpins some of the most influential hypotheses concerning potentially modifiable risk exposures, it is important to exclude other possible explanations for the phenomenon. Methods: Here we sought to determine whether the season of birth effect reflects gene-environment confounding rather than a pathogenic process indexing environmental exposure. We directly measured, in 136 538 participants from the UK Biobank (UKBB), the burdens of common schizophrenia risk alleles and of copy number variants known to increase the risk for the disorder, and tested whether these were correlated with a season of birth. Results: Neither genetic measure was associated with season or month of birth within the UKBB sample. Conclusions: As our study was highly powered to detect small effects, we conclude that the season of birth effect in schizophrenia reflects a true pathogenic effect of environmental exposure. [ABSTRACT FROM AUTHOR]

Background: Cognitive impairment is strongly linked with persistent disability in people with mood disorders, but the factors that explain cognitive impairment in this population are unclear.Aims: To estimate the total effect of (a) bipolar disorder and (b) major depression on cognitive function, and the magnitude of the effect that is explained by potentially modifiable intermediate factors.Method: Cross-sectional study using baseline data from the UK Biobank cohort. Participants were categorised as having bipolar disorder (n = 2709), major depression (n = 50 975) or no mood disorder (n = 102 931 and n = 105 284). The outcomes were computerised tests of reasoning, reaction time and memory. The potential mediators were cardiometabolic disease and psychotropic medication. Analyses were informed by graphical methods and controlled for confounding using regression, propensity score-based methods and G-computation.Results: Group differences of small magnitude were found on a visuospatial memory test. Z-score differences for the bipolar disorder group were in the range -0.23 to -0.17 (95% CI -0.39 to -0.03) across different estimation methods, and for the major depression group they were approximately -0.07 (95% CI -0.10 to -0.03). One-quarter of the effect was mediated via psychotropic medication in the bipolar disorder group (-0.05; 95% CI -0.09 to -0.01). No evidence was found for mediation via cardiometabolic disease.Conclusions: In a large community-based sample in middle to early old age, bipolar disorder and depression were associated with lower visuospatial memory performance, in part potentially due to psychotropic medication use. Mood disorders and their treatments will have increasing importance for population cognitive health as the proportion of older adults continues to grow.Declaration Of Interest: I.J.D. is a UK Biobank participant. J.P.P. is a member of the UK Biobank Steering Committee. [ABSTRACT FROM AUTHOR]

Depression and chronic inflammatory medical conditions have been linked to impaired cognitive ability. However despite frequent comorbidity, their combined association with cognitive ability has rarely been examined. This study examined associations between self-reported depression and chronic inflammatory diseases and their interaction with cognitive performance in 456,748 participants of the UK Biobank, adjusting for sociodemographic and lifestyle factors. Numbers with available data ranged from 94,899 to 453,208 depending on the cognitive test. Self-reported depression was associated with poorer performance compared to controls in several cognitive tests (fully adjusted models, reaction time: B = 6.08, 95% CI = 5.09, 7.07; pairs matching: incidence rate ratio = 1.02, 95% CI = 1.02, 1.03; Trail Making Test B: B = 1.37, 95% CI = 0.88, 1.87; Digit Symbol Substitution Test (DSST): B = −0.35, 95% CI = −0.44, −0.27). Self-reported chronic inflammatory conditions were associated with slower reaction time (B = 3.79, 95% CI = 2.81, 4.78) and lower DSST scores (B = −0.21, 95% CI = −0.30, −0.13). No interaction effects were observed. In this large, population-based study we provide evidence of lower cognitive performance in both depression and a comprehensive category of chronic inflammatory conditions. Results are consistent with additive effects of both types of disorder on cognitive ability. Clinicians should be aware of such effects, particularly as cognitive impairment is linked to poorer disease outcomes and quality of life. [ABSTRACT FROM AUTHOR]

Background: Studies involving clinically recruited samples show that genetic liability to schizophrenia overlaps with that for several psychiatric disorders including bipolar disorder, major depression and, in a population study, anxiety disorder and negative symptoms in adolescence.AimsWe examined whether, at a population level, association between schizophrenia liability and anxiety disorders continues into adulthood, for specific anxiety disorders and as a group. We explored in an epidemiologically based cohort the nature of adult psychopathology sharing liability to schizophrenia.Method: Schizophrenia polygenic risk scores (PRSs) were calculated for 590 European-descent individuals from the Christchurch Health and Development Study. Logistic regression was used to examine associations between schizophrenia PRS and four anxiety disorders (social phobia, specific phobia, panic disorder and generalised anxiety disorder), schizophrenia/schizophreniform disorder, manic/hypomanic episode, alcohol dependence, major depression, and - using linear regression - total number of anxiety disorders. A novel population-level association with hypomania was tested in a UK birth cohort (Avon Longitudinal Study of Parents and Children).Results: Schizophrenia PRS was associated with total number of anxiety disorders and with generalised anxiety disorder and panic disorder. We show a novel population-level association between schizophrenia PRS and manic/hypomanic episode.Conclusions: The relationship between schizophrenia liability and anxiety disorders is not restricted to psychopathology in adolescence but is present in adulthood and specifically linked to generalised anxiety disorder and panic disorder. We suggest that the association between schizophrenia liability and hypomanic/manic episodes found in clinical samples may not be due to bias.Declarations of interestNone. [ABSTRACT FROM AUTHOR]

Background Cannabis use in young people is common and associated with psychiatric disorders. However, the prospective link between cannabis use and bipolar disorder symptoms has rarely been investigated. The study hypothesis was that adolescent cannabis use is associated with hypomania in early adulthood via several potential etiological pathways. Methods Data were used from the Avon Longitudinal Study of Parents and Children, a UK birth cohort study. The prospective link between cannabis use at age 17 and hypomania at age 22–23 years was tested using regression analysis, adjusted for gender, early environmental risk factors, alcohol and drug use, and depression and psychotic symptoms at age 18 years. Path analysis examined direct and indirect effects of the link and whether gender, childhood family adversity, or childhood abuse are associated with hypomania via an increased risk of cannabis use. Results Data were available on 3370 participants. Cannabis use at least 2–3 times weekly was associated with later hypomania (OR = 2.21, 95% CI = 1.49–3.28) after adjustment. There was a dose–response relationship (any use vs weekly). Cannabis use mediated the association of both childhood sexual abuse and hypomania, and male gender and hypomania. The cannabis use-hypomania link was not mediated by depression or psychotic symptoms. Conclusions Adolescent cannabis use may be an independent risk factor for future hypomania, and the nature of the association suggests a potential causal link. Cannabis use mediates the link between childhood abuse and future hypomania. As such it might be a useful target for indicated prevention of hypomania. [ABSTRACT FROM AUTHOR]

Abstract: British sociologists have long been interested in youth sub‐cultures. However British sociologists have tended to focus on working class subcultures and avoided engagement with exclusive sub‐cultures of elite social groups. This article seeks to attend to this gap by examining the subculture of a British elite: ex‐public school students at select universities in the UK in the twenty‐first century. This group consists of a relatively small group of young adults, aged between 18 and 23, who attended public schools, especially one of the nine Clarendon schools (Eton, Winchester, Westminster, St. Paul's, Merchant Taylor's, Shrewsbury, Rugby, Harrow and Charterhouse), and were students at a selective group of British universities, primarily Oxford and Cambridge, Durham, Bristol, Exeter, Bath, Manchester, St Andrews and Edinburgh. The article examines the way in which this group has reconfigured and re‐constituted itself in the face of globalizing challenges. Specifically, it examines the way in which participation of ex‐public school students in events run by and under the patronage of the high street retailing company, Jack Wills, has played a galvanising role for this group in the last decade. The Jack Wills crowd is an example of how some young adults form exclusive social networks and reproduce prevailing forms of privilege. The social networks built around the Jack Wills subculture is likely to provide them with advantages in the job market through a prodigious network of connections and patrons. The Jack Wills subculture potentially contributions to the socio‐economic reproduction of the higher professional middle classes. [ABSTRACT FROM AUTHOR]

Background: Educating doctors is expensive and poor performance by future graduates can literally cost lives. Whilst the practice of medicine is highly evidence based, medical education is much less so. Research on medical school selection, undergraduate progression, Fitness to Practise (FtP) and postgraduate careers has been hampered across the globe by the challenges of uniting the data required. This paper describes the creation, structure and access arrangements for the first UK-wide attempt to do so. Overview: A collaborative approach has created a research database commencing with all entrants to UK medical schools in 2007 and 2008 (UKMED Phase 1). Here the content is outlined, governance arrangements considered, system access explained, and the potential implications of this new resource discussed. The data currently include achievements prior to medical school entry, admissions tests, graduation point information and also all subsequent data collected by the General Medical Council, including FtP, career progression, annual National Training Survey (NTS) responses, career choice and postgraduate exam performance data. UKMED has grown since the pilot phase with additional datasets; all subsequent years of students/trainees and stronger governance processes. The inclusion of future cohorts and additional information such as admissions scores or bespoke surveys or assessments is now being piloted. Thus, for instance, new scrutiny can be applied to selection techniques and the effectiveness of educational interventions. Data are available free of charge for approved studies from suitable research groups worldwide. Conclusion: It is anticipated that UKMED will continue on a rolling basis. This has the potential to radically change the volume and types of research that can be envisaged and, therefore, to improve standards, facilitate workforce planning and support the regulation of medical education and training. This paper aspires to encourage proposals to utilise this exciting resource. [ABSTRACT FROM AUTHOR]

Digital data is constitutive of many forms of popular culture and user engagement. How data feeds back and is integrated into practice is of critical importance when it comes to analysing the place of the ‘self’ in contemporary culture. This article provides an account of video-blogging on YouTube. It takes as its case study three UK ‘YouTube Celebrities’ – Charlie McDonnell, Chris Kendall and Benjamin Cook – and focuses upon three vlogs which all express disquiet with their celebrity. This unease is articulated in relation to the digital consummation of self YouTube provides its users. Through a textual and performance analysis the article explores the cultural heritage of the vlog in what Charles Taylor calls western culture’s ‘expressive turn’. It argues that what a digitised popular culture gives us is a novel space to rework longstanding cultural ideals around the self, individuality and self-expression. [ABSTRACT FROM AUTHOR]

Background: the apolipoprotein (APOE) e4 locus is a genetic risk factor for dementia. Carriers ofthe e4 allele may be more vulnerable to conditions that are independent risk factors for cognitive decline, such as cardiometabolic diseases. Objective: we tested whether any association with APOE e4 status on cognitive ability was larger in older ages or in those with cardiometabolic diseases. Subjects: UK Biobank includes over 500,000 middle- and older aged adults who have undergone detailed medical and cognitive phenotypic assessment. Around 150,000 currently have genetic data. We examined 111,739 participants with complete genetic and cognitive data. Methods: baseline cognitive data relating to information processing speed, memory and reasoning were used. We tested for interactions with age and with the presence versus absence of type 2 diabetes (T2D), coronary artery disease (CAD) and hypertension. Results: in several instances, APOE e4 dosage interacted with older age and disease presence to affect cognitive scores. When adjusted for potentially confounding variables, there was no APOE e4 effect on the outcome variables. Conclusions: future research in large independent cohorts should continue to investigate this important question, which has potential implications for aetiology related to dementia and cognitive impairment. [ABSTRACT FROM AUTHOR]

UK Biobank includes 502,649 middle- and older-aged adults from the general population who have undergone detailed phenotypic assessment. The majority of participants completed tests of cognitive functioning, and on average four years later a sub-group of N = 20,346 participants repeated most of the assessment. These measures will be used in a range of future studies of health outcomes in this cohort. The format and content of the cognitive tasks were partly novel. The aim of the present study was to validate and characterize the cognitive data: to describe the inter-correlational structure of the cognitive variables at baseline assessment, and the degree of stability in scores across longitudinal assessment. Baseline cognitive data were used to examine the inter-correlational/factor-structure, using principal components analysis (PCA). We also assessed the degree of stability in cognitive scores in the subsample of participants with repeat data. The different tests of cognitive ability showed significant raw inter-correlations in the expected directions. PCA suggested a one-factor solution (eigenvalue = 1.60), which accounted for around 40% of the variance. Scores showed varying levels of stability across time-points (intraclass correlation range = 0.16 to 0.65). UK Biobank cognitive data has the potential to be a significant resource for researchers looking to investigate predictors and modifiers of cognitive abilities and associated health outcomes in the general population. [ABSTRACT FROM AUTHOR]

Background: Comorbid chronic pain and depression is a challenging dyad of conditions to manage in primary care and reporting has shown to vary by ethnic group. Whether the relationship between depression and chronic pain varies by ethnicity is unclear. This study aims to explore chronic pain and depression reporting across ethnic groups and examine whether this association differs, independently of potential confounding factors. Methods: Cross-sectional study of UK Biobank participants with complete data on chronic pain and probable lifetime history of depression, who reported their ethnic group as White, Asian/Asian British or Black/Black British. Chronic pain classification: present if participants had ≥ 1 site of body pain (up to seven sites or "pain all over the body" could be selected) that lasted ≥ 3 months; extent of chronic pain categories: 0, 1, 2-3, 4-7 sites or pain all over the body. Probable depression classification: an algorithm of low mood, anhedonia and help-seeking behaviour. Relationship between depression and presence/extent of chronic pain assessed using logistic/ multinomial regression models (odds ratio (OR); relative risk ratio (RRR), 95 % confidence intervals), adjusted for sociodemographic, lifestyle, and morbidity factors; and a final adjustment for current depressive symptoms. Results: The number of participants eligible for inclusion was 144,139: 35,703 (94 %) White, 4539 (3 %) Asian, and 3897 (3 %) Black. Chronic pain was less (40.5 %, 45.8 %, 45.0 %, respectively) and depression more (22.1 %, 12.9 %, 13.8 %, respectively) commonly reported in White participants than Asian and Black participants. Statistically significant associations between depression and presence/extent of chronic pain persisted following adjustment for potential confounding variables; this relationship was strongest for Black participants (presence of chronic pain: OR 1.86 (1.52, 2.27); RRR 1 site 1.49 (1.16, 1.91), 2-3 sites 1.98 (1.53, 2.56), 4-7 sites 3.23 (2.09, 4.99), pain all over the body 3.31 (2.05, 5.33). When current depressive symptoms were considered these relationships were attenuated. Conclusions: Chronic pain and depression reporting varies across ethnic groups. Differences in health seeking behaviour between ethnic groups may impact on the results reported. Clinicians, particularly in primary care, need to be aware of the cultural barriers within certain ethic groups to expressing concern over mood and to consider their approach accordingly. [ABSTRACT FROM AUTHOR]

Background Chronic pain has a strong association with major depressive disorder (MDD), but there is a relative paucity of studies on the association between chronic multisite pain and bipolar disorder (BD). Such studies are required to help elucidate the complex biological and psychological overlap between pain and mood disorders. The aim of this study is to investigate the relationship between chronic multisite pain and mood disorder across the unipolar-bipolar spectrum. Methods We conducted a cross-sectional study of 149,611 UK Biobank participants. Self-reported depressive and bipolar features were used to categorise participants into MDD and BD groups and a non-mood disordered comparison group. Multinomial logistic regression was used to establish whether there was an association between extent of chronic pain (independent variable) and mood disorder category (dependent variable), using no pain as the referent category, and adjusting for a wide range of potential sociodemographic, lifestyle and comorbidity confounders. Results Multisite pain was significantly more prevalent in participants with BD and MDD, for example, 4-7 pain sites: BD 5.8%, MDD 4.5%, and comparison group 1.8% (p < 0.001). A relationship was observed between extent of chronic pain and risk of BD and persisted after adjusting for confounders (relative to individuals with no chronic pain): 2-3 sites RRR of BD 1.84 (95% CI 1.61, 2.11); 4-7 sites RRR of BD 2.39 (95%CI 1.88, 3.03) and widespread pain RRR of BD 2.37 (95%CI 1.73, 3.23). A similar relationship was observed between chronic pain and MDD: 2-3 sites RRR of MDD 1.59 (95%CI 1.54, 1.65); 4-7 sites RRR of MDD 2.13 (95%CI 1.98, 2.30); widespread pain RRR of MDD 1.86 (95%CI 1.66, 2.08). Conclusions Individuals who report chronic pain and multiple sites of pain are more likely to have MDD and are at higher risk of BD. These findings highlight an important aspect of comorbidity in MDD and BD and may have implications for understanding the shared neurobiology of chronic pain and mood disorders. [ABSTRACT FROM AUTHOR]

Background The Quality and Outcomes Framework (QOF) has specific targets for body mass index (BMI) and blood pressure recording in major mental illness (MMI), diabetes, and chronic kidney disease (CKD). Although aspects of MMI (schizophrenia, bipolar disorder, and related psychoses) are incentivised, barriers to care may occur. Aim To compare payment, population achievement, and exception rates for blood pressure and BMI recording in MMI relative to diabetes and CKD across the UK. Design and setting Analysis of 2012/2013 QOF data from 9731 UK general practices 2 years after the introduction of the mental health, BMI, and blood pressure QOF indicators. Method Payment, exception, and population achievement rates for the MMI and CKD blood pressure indicators and the MMI and diabetes BMI indicators were calculated and compared. Results UK payment and population achievement rates for BMI recording for MMI were significantly lower than for diabetes (payment: 92.7% versus 95.5% and population achievement: 84.0% versus 92.5%, P<0.001) and exception rates were higher (8.1% versus 2.0%, P<0.001). For blood pressure recording, UK payment and population achievement rates were significantly lower for MMI than for CKD (94.1% versus 97.8% and 87.0% versus 97.1%, P<0.001), while exception rate was higher (6.5% versus 0.0%, P<0.001). This was observed for all countries. Compared with England, Northern Ireland had higher population achievement rates for both mental health indicators, whereas Scotland and Wales had lower rates. There were no cross-jurisdiction differences for CKD and diabetes. Conclusion Differences in payment, exception, and population achievement rates for blood pressure and BMI recording for MMI relative to CKD and diabetes were observed across the UK. These findings suggest potential inequalities in the monitoring of physical health in MMI within the UK primary care system. [ABSTRACT FROM AUTHOR]

Background Previous studies on the association between adiposity and mood disorder have produced contradictory results, and few have used measurements other than body mass index (BMI). We examined the association between probable major depression and several measurements of adiposity: BMI, waist circumference (WC), waist-hip-ratio (WHR), and body fat percentage (BF%). Methods We conducted a cross-sectional study using baseline data on the sub-group of UK Biobank participants who were assessed for mood disorder. Multivariate logistic regression models were used, adjusting for potential confounders including: demographic and life-style factors, comorbidity and psychotropic medication. Results Of the 140,564 eligible participants, evidence of probable major depression was reported by 30,145 (21.5%). The fully adjusted odds ratios (OR) for obese participants were 1.16 (95% confidence interval (CI) 1.12, 1.20) using BMI, 1.15 (95% CI 1.11, 1.19) using WC, 1.09 (95% CI 1.05, 1.13) using WHR and 1.18 (95% CI 1.12, 1.25) using BF% (all p < 0.001). There was a significant interaction between adiposity and gender (p = 0.001). Overweight women were at increased risk of depression with a dose response relationship across the overweight (25.0-29.9 kg/m²), obese I (30.0-34.9 kg/m²), II (35.0-39.9 kg/m²) and III (≥40.0 kg/m²) categories; fully adjusted ORs 1.14, 1.20, 1.29 and 1.48, respectively (all p < 0.001). In contrast, only obese III men had significantly increased risk of depression (OR 1.29, 95% CI 1.08, 1.54, p = 0.006). Conclusion Adiposity was associated with probable major depression, irrespective of the measurement used. The association was stronger in women than men. Physicians managing overweight and obese women should be alert to this increased risk. [ABSTRACT FROM AUTHOR]

Background Obesity is known to increase the risk of many diseases and reduce overall quality of life. This study examines the relationship with self-reported health (SRH) and happiness. Methods We conducted a cross-sectional study of the 163 066 UK Biobank participants who completed the happiness rating. The association between adiposity and SRH and happiness was examined using logistic regression. SRH was defined as good (excellent, good), or poor (fair, poor). Self-reported happiness was defined as happy (extremely, very, moderately) or unhappy (moderately, very, extremely). Results Poor health was reported by 44 457 (27.3%) participants. The adjusted ORs for poor health were 3.86, 2.92, 2.60 and 6.41 for the highest, compared with lowest, deciles of Body Mass Index, waist circumference, waist to hip ratio and body fat percent, respectively. The associations were stronger in men (p<0.001). Overall, 7511 (4.6%) participants felt unhappy, and only class III obese participants were more likely to feel unhappy (adjusted OR 1.33, 95% CI 1.15 to 1.53, p<0.001) but the associations differed by sex (p<0.001). Among women, there was a significant association between unhappiness and all levels of obesity. By contrast, only class III obese men had significantly increased risk and overweight and class I obese men were less likely to be unhappy. Conclusions Obesity impacts adversely on happiness as well as health, but the association with unhappiness disappeared after adjustment for self-reported health, indicating this may be mediated by health. Compared with obese men, obese women are less likely to report poor health, but more likely to feel unhappy. [ABSTRACT FROM AUTHOR]

Background Major depressive disorder (MDD) is often a chronic disorder with relapses usually detected and managed in primary care using a validated depression symptom questionnaire. However, for individuals with recurrent depression the choice of which questionnaire to use and whether a shorter measure could suffice is not established. Aim To compare the nine-item Patient Health Questionnaire (PHQ-9), the Beck Depression Inventory, and the Hospital Anxiety and Depression Scale against shorter PHQ-derived measures for detecting episodes of DSM-IV major depression in primary care patients with recurrent MDD. Design and setting Diagnostic accuracy study of adults with recurrent depression in primary care predominantly from Wales Method Scores on each of the depression questionnaire measures were compared with the results of a semi-structured clinical diagnostic interview using Receiver Operating Characteristic curve analysis for 337 adults with recurrent MDD. Results Concurrent questionnaire and interview data were available for 272 participants. The onemonth prevalence rate of depression was 22.2%. The area under the curve (AUC) and positive predictive value (PPV) at the derived optimal cut-off value for the three longer questionnaires were comparable (AUC = 0.86-0.90, PPV = 49.4-58.4%) but the AUC for the PHQ-9 was significantly greater than for the PHQ-2. However, by supplementing the PHQ-2 score with items on problems concentrating and feeling slowed down or restless, the AUC (0.91) and the PPV (55.3%) were comparable with those for the PHQ-9. Conclusion A novel four-item PHQ-based questionnaire measure of depression performs equivalently to three longer depression questionnaires in identifying depression relapse in patients with recurrent MDD. [ABSTRACT FROM AUTHOR]

Objectives: UK Biobank is a landmark cohort of over 500,000 participants which will be used to investigate genetic and non-genetic risk factors for a wide range of adverse health outcomes. This is the first study to systematically assess the prevalence and validity of proposed criteria for probable mood disorders within the cohort (major depression and bipolar disorder). Methods: This was a descriptive epidemiological study of 172,751 individuals assessed for a lifetime history of mood disorder in relation to a range of demographic, social, lifestyle, personality and health-related factors. The main outcomes were prevalence of a probable lifetime (single) episode of major depression, probable recurrent major depressive disorder (moderate), probable recurrent major depressive disorder (severe), probable bipolar disorder and no history of mood disorder (comparison group). Outcomes were compared on age, gender, ethnicity, socioeconomic status, educational attainment, functioning, self-reported health status, current depressive symptoms, neuroticism score, smoking status and alcohol use. Results: Prevalence rates for probable single lifetime episode of major depression (6.4%), probable recurrent major depression (moderate) (12.2%), probable recurrent major depression (severe) (7.2%) and probable bipolar disorder (1.3%) were comparable to those found in other population studies. The proposed diagnostic criteria have promising validity, with a gradient in evidence from no mood disorder through major depression and probable bipolar disorder in terms of gender distribution, socioeconomic status, self-reported health rating, current depressive symptoms and smoking. Significance: The validity of our proposed criteria for probable major depression and probable bipolar disorder within this cohort are supported by these cross-sectional analyses. Our findings are likely to prove useful as a framework for a wide range of future genetic and non-genetic studies. [ABSTRACT FROM AUTHOR]

Bipolar disorder is a complex condition characterised by both manic and depressive episodes. Here the authors discuss the challenges faced in both diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Purpose: Supervisors play a key role in the development of postgraduate medical trainees both in the oversight of their day-to-day clinical practice but also in the support of their learning experiences. In the UK, there has been a clear distinction made between these two activities. In this article, we report on the development of a web-based multisource feedback (MSF) tool for educational supervisors in the London Deanery, an organisation responsible for 20% of the UK's doctors and dentists in training. Methods: A narrative review of the literature generated a question framework for a series of focus groups. Data were analysed using an interpretative thematic approach and the resulting instrument piloted online. Instrument performance was analysed using a variety of tools including factor analysis, generalisability theory and analysis of performance in the first year of implementation. Results: Two factors were initially identified. Three questions performed inadequately and were subsequently discarded. Educational supervisors scored well, generally rating themselves lower than they were by their trainees. The instrument was launched in July 2010, requiring five respondents to generate a summated report, with further validity evidence collated over the first year if implementation. Conclusions: Arising out of a robust development process, the London Deanery MSF instrument for educational supervisors is a tool that demonstrates considerable evidence of validity and can provide supervisors with useful evidence of their effectiveness. [ABSTRACT FROM AUTHOR]

The article presents a study on the impact of bullying trainee doctors in Great Britain. The learning ability and safety of patients are primarily affected when senior colleagues bully their trainee doctors. It suggests that trainee doctors should not be submitted to behaviours that weaken their self-confidence and professional self-esteem. It also provides a definition of bullying published in the recent report of the British Medical Association (BMA).

Context The West Midlands Matching Scheme has been in operation since 1999 and is one of a number of schemes used for the allocation of pre-registration house officer positions in the UK. Method and Results A questionnaire was distributed amongst candidates applying to the scheme in 2000. A response rate of 73·7% was obtained (160 replies from a sample population of 217). Half the responders reported to be dissatisfied with the explanation of the matching scheme given. A total of 66·6% were satisfied with the scheme being run via the Internet and E-mail. For 6-month positions in medicine, 85% of the candidates were happy with the job they had received. The figures for surgical jobs were similar and for rotations even higher. However, 23·8% of the sample was missing one or two jobs at the end of the matching process. This figure was still high when non-responders were taken into account. This group was not happy with the way in which the remaining jobs were distributed to them (71% dissatisfied). Conclusion Although the matching scheme matched a high proportion of responders to jobs they were satisfied with, there was a significant group without jobs who were unhappy with the scheme. Some of those with jobs were also dissatisfied with the jobs they had received. Both problems should be addressed in future schemes. Further work in this area should examine the characteristics of the group without jobs and look at the success of other schemes in order to determine the optimal way in which to allocate PRHO jobs. [ABSTRACT FROM AUTHOR]

The purpose of this research was to assess demographic differences in exposure to traumatic events and fear of crime. This is part of a larger project that assessed the impact of the 1992 Los Angeles civil disturbances on psychological functioning. Random digit dialing methods were used to obtain an adult household probability sample (age 18 or older) representative of the targeted region (Los Angeles County). A total of 1200 individuals completed a 40-minute comprehensive telephone interview. Four hundred interviews were sampled from South Central (the area most heavily affected by the rioting), and 800 were sampled from the remainder of L.A. County. A series of chi-square analyses indicated that there were differences in (a) prevalence of lifetime and past year victimization, (b) perception of neighborhood problems, (c) exposure to the disturbances, and (d) fear of crime as a function of demographic characteristics (i.e., gender, race, ethnicity, community). A hierarchical multiple regression was conducted using demographic variables, victimization, and exposure to the disturbances to predict fear of crime. Results indicated that demographic variables were significantly predictive of crime fear, but that report of neighborhood problems was the strongest predictor. Additionally, exposure to the disturbances remained a significant predictor of crime fear after controlling for the effects of victimization, demographics, and neighborhood problems. Results suggest that while diverse community, race, ethnicity, and gender variables contribute to differences in crime fear, neighborhood problems may be the most important predictor across all groups of subjects. © 2000 John Wiley & Sons, Inc. [ABSTRACT FROM AUTHOR]

Background: The link between cardiometabolic and psychiatric illness has long been attributed to human behaviour, however recent research highlights shared biological mechanisms. The ASTN2 locus has been previously implicated in psychiatric and cardiometabolic traits, therefore this study aimed to systematically investigate the genetic architecture of ASTN2 in relation to a wide range of relevant traits. Methods: Baseline questionnaire, assessment and genetic data of 402111 unrelated white British ancestry individuals from the UK Biobank was analysed. Genetic association analyses were conducted using PLINK 1.07, assuming an additive genetic model and adjusting for age, sex, genotyping chip, and population structure. Conditional analyses and linkage disequilibrium assessment were used to determine whether cardiometabolic and psychiatric signals were independent. Results: Associations between genetic variants in the ASTN2 locus and blood pressure, total and central obesity, neuroticism, anhedonia and mood instability were identified. All analyses support the independence of the cardiometabolic traits from the psychiatric traits. In silico analyses provide support for the central obesity signal acting through ASTN2, however most of the other signals are likely acting through other genes in the locus. Conclusions: Our systematic analysis demonstrates that ASTN2 has pleiotropic effects on cardiometabolic and psychiatric traits, rather than contributing to shared pathology. [ABSTRACT FROM AUTHOR]

Examines the different employment structures in leisure and retail organizations in the light of the recent Sunday Trading Act, 1994. Considers the make-up of staff; training methods; rates of pay and changing customer demand patterns in order to draw comparisons and identify possible emerging trends. Asks the question as to whether retail outlets and their leisure counterparts trade in similar conditions and what the impact will be on the Sunday labour pool and levels of pay. Draws interesting employment comparisons between leisure, part of the hospitality industry, and retailing as their opening times overlap to a greater degree. Finds that, consequently, they are increasingly competing for labour from similar sources. [ABSTRACT FROM AUTHOR]

The article focuses on how weather events affect liver fluke infections. It states that rainfall and temperature are related to an increase in the infection in livestock in Great Britain. It mentions that infection of snails is associated with fluke risk in the country. It highlights that metacercarial cysts which carry the infection survive in winter flooding.

People born in winter and early spring are at an elevated risk for schizophrenia [1 – 4]. Although the effect is small, with an increase in risk of about around 10%, this season of birth effect is one of the most robust findings in schizophrenia epidemiology [5]. It has also been influential in developing hypotheses of schizophrenia pathogenesis, forming one of the central planks of the viral infection hypothesis of the disorder [6] as well as other less intensively investigated putative mechanisms including vitamin D deficiency during fetal development [7]. However, at present, the mechanisms underpinning this season of birth effect are unknown. We implement PRS analysis of the UK Biobank (UKBB) to determine whether season of birth is associated with genetic risk for schizophrenia. We generated schizophrenia PRS for every participant in the UKBB (June 2015 release, N=136,538) and tested whether this score is associated with month or season of birth. As a secondary test of the plausibility of season of birth being a genetically correlated confound, we also conducted a GWAS of season of birth as a binary phenotype, comparing winter/spring births with summer/autumn. Our aim was to estimate heritability of season of birth as a phenotype. We found no association between schizophrenia PRS and season of birth in the UK Biobank sample and no differences in schizophrenia risk scores with respect to month of birth. No SNPs were associated with season of birth at genome-wide significance, there was no evidence for inflation in the test statistics indicative of polygenic inheritance and no evidence that SNP heritability contributed to this trait (total liability scale h2=-0.002 SE=0.0052 as estimated by LD-Score regression). In this study, we examined seasonality in regard to genetic risk to schizophrenia within UK Biobank. We used the largest schizophrenia dataset to date for identification of genetic risk loci and one of the largest available population cohorts to generate schizophrenia PRS and test for seasonal differences in genetic liability to schizophrenia. We found no trends of elevated schizophrenia polygenic risk scores in people born in winter or spring. These results were further supported by a lack of evidence that seasonality is a heritable trait. Since the PRS analysis and heritability estimates were based upon common SNPs, we don't exclude a possible role for rare SNPs, however the frequencies of rare CNVs, linked to neurodevelopmental disorders, also did not differ by season of birth. [ABSTRACT FROM AUTHOR]