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UK Biobank is a well-characterised cohort of over 500 000 participants including genetics, environmental data and imaging. An online mental health questionnaire was designed for UK Biobank participants to expand its potential.
Describe the development, implementation and results of this questionnaire.
An expert working group designed the questionnaire, using established measures where possible, and consulting a patient group. Operational criteria were agreed for defining likely disorder and risk states, including lifetime depression, mania/hypomania, generalised anxiety disorder, unusual experiences and self-harm, and current post-traumatic stress and hazardous/harmful alcohol use.
A total of 157 366 completed online questionnaires were available by August 2017. Participants were aged 45–82 (53% were ≥65 years) and 57% women. Comparison of self-reported diagnosed mental disorder with a contemporary study shows a similar prevalence, despite respondents being of higher average socioeconomic status. Lifetime depression was a common finding, with 24% (37 434) of participants meeting criteria and current hazardous/harmful alcohol use criteria were met by 21% (32 602), whereas other criteria were met by less than 8% of the participants. There was extensive comorbidity among the syndromes. Mental disorders were associated with a high neuroticism score, adverse life events and long-term illness; addiction and bipolar affective disorder in particular were associated with measures of deprivation.
The UK Biobank questionnaire represents a very large mental health survey in itself, and the results presented here show high face validity, although caution is needed because of selection bias. Built into UK Biobank, these data intersect with other health data to offer unparalleled potential for crosscutting biomedical research involving mental health.
UK Biobank is a well-characterised cohort of over 500 000 participants that offers unique opportunities to investigate multiple diseases and risk factors.
An online mental health questionnaire completed by UK Biobank participants was expected to expand the potential for research into mental disorders.
An expert working group designed the questionnaire, using established measures where possible, and consulting with a patient group regarding acceptability. Case definitions were defined using operational criteria for lifetime depression, mania, anxiety disorder, psychotic-like experiences and self-harm, as well as current post-traumatic stress and alcohol use disorders.
157 366 completed online questionnaires were available by August 2017. Comparison of self-reported diagnosed mental disorder with a contemporary study shows a similar prevalence, despite respondents being of higher average socioeconomic status than the general population across a range of indicators. Thirty-five per cent (55 750) of participants had at least one defined syndrome, of which lifetime depression was the most common at 24% (37 434). There was extensive comorbidity among the syndromes. Mental disorders were associated with high neuroticism score, adverse life events and long-term illness; addiction and bipolar affective disorder in particular were associated with measures of deprivation.
The questionnaire represents a very large mental health survey in itself, and the results presented here show high face validity, although caution is needed owing to selection bias. Built into UK Biobank, these data intersect with other health data to offer unparalleled potential for crosscutting biomedical research involving mental health.
Declaration of interest
G.B. received grants from the National Institute for Health Research during the study; and support from Illumina Ltd. and the European Commission outside the submitted work. B.C. received grants from the Scottish Executive Chief Scientist Office and from The Dr Mortimer and Theresa Sackler Foundation during the study. C.S. received grants from the Medical Research Council and Wellcome Trust during the study, and is the Chief Scientist for UK Biobank. M.H. received grants from the Innovative Medicines Initiative via the RADAR-CNS programme and personal fees as an expert witness outside the submitted work.
Understanding the origin of modern communities is a fundamental goal of ecology, but reconstructing communities with durations of 103–106 years requires data from the fossil record. Early Pliocene to latest Pleistocene faunas and sediments in the Meade Basin and modern soils and rodents from the same area are used to examine the role of environmental change in the emergence of the modern community. Paleoenvironmental proxies measured on modern surface soils and paleosols are described, and faunal dynamics of fossil rodents are discussed. Mean annual precipitation (MAP) was estimated from elemental concentrations and magnetic properties, and warm-season temperature and δ18O of soil water was estimated using carbonate isotope paleothermometry on pedogenic nodules. MAP and temperature estimates from paleosols exhibit no short-term variability, no long-term trends, and generally bracket modern values. Estimated soil water δ18O values increased through time, suggesting aridification played a role in the evolution of the regional grassland ecosystem. Carbon isotope analyses of biomarkers are used to examine the abundance of C4 grasses, which suggest more C4 biomass and more variability in C4 biomass than carbonate proxies. Rodent species richness remained constant due to balanced rates of extinction and immigration, both of which show episodic spikes consistent with a balance between forcing mechanisms that result in equilibrium on long time scales. Overall, these results suggest that different mechanisms of faunal change may be acting at different time scales, although the stratigraphic resolution of paleoenvironmental proxies needs to be increased, and body size and dietary distributions of rodents need to be determined before which processes of change are most important can be decided.
This study introduces a special series on validity studies of the Cognition Battery (CB) from the U.S. National Institutes of Health Toolbox for the Assessment of Neurological and Behavioral Function (NIHTB) (Gershon, Wagster et al., 2013) in an adult sample. This first study in the series describes the sample, each of the seven instruments in the NIHTB-CB briefly, and the general approach to data analysis. Data are provided on test–retest reliability and practice effects, and raw scores (mean, standard deviation, range) are presented for each instrument and the gold standard instruments used to measure construct validity. Accompanying papers provide details on each instrument, including information about instrument development, psychometric properties, age and education effects on performance, and convergent and discriminant construct validity. One study in the series is devoted to a factor analysis of the NIHTB-CB in adults and another describes the psychometric properties of three composite scores derived from the individual measures representing fluid and crystallized abilities and their combination. The NIHTB-CB is designed to provide a brief, comprehensive, common set of measures to allow comparisons among disparate studies and to improve scientific communication. (JINS, 2014, 20, 1–12)
This chapter lists the factors that differentiate pharmacogenomics from conventional biomarker research on a strategic, operational, and technical level. The "-omics" technologies and conventional methods are mutually complementary approaches in the search for biomarkers. The genetic component of multiple sclerosis (MS) risk has been the focus of study for a long time, and beyond the classic association with the MHC locus, seven genome-wide association studies (GWAS) reported in recent years have helped identify other candidate genes, such as the IL-7 and IL-2 receptors. Compared with DNA- and RNA-based analyses, proteomics and metabolomics are less advanced techniques. The requirements for establishing a comprehensive and integrated matrix of genotype/phenotype interaction are: development of technologies for proteomics and metabolomics to the same level as genotyping and trancriptomics, development of bioinformatic tools, and development of longitudinally studied cohorts characterized using standardized, high-quality clinical and paraclinical methods.
The pharmacokinetics of a single I.V dose of natalizumab were studied in a phase 1, dose-escalation study in 28 multiple sclerosis (MS) patients. As part of the clinical trial program to establish the pharmacokinetic/pharmacodynamic and safety profiles of natalizumab, four Phase 1, dose-finding studies were conducted. An additional Phase 2 study was conducted to evaluate the safety and efficacy of natalizumab in combination with glatiramer acetate (GA). One of the recommendations of the therapeutics and technology assessment subcommittee of the AAN about the use of natalizumab was to carefully monitor patients receiving natalizumab to establish its long-term safety i.e. the true risk of progressive multifocal leukoencephalopathy (PML). Large Phase 3 trials of natalizumab alone or in combination with interferon (IFN)β-1a show that natalizumab reduces the progression of disability, and dramatically reduces the frequency of relapses and magnetic resonance imaging (MRI) lesion formation in patients with relapsing MS.
The pleiotropic effect of the rose-comb gene (R) on fertility when combined with artificial selection against the single-comb type (r) results in an interesting example of operational over-dominance. An evaluation of the equilibrium frequency of the rose-comb gene based on this over-dominance concept provides a plausible explanation for the relatively high frequency of single-comb birds appearing in the Wyandotte breed of fowls.
To compare the efficacy of computed tomographic angiography (CTA) to that of digital subtraction angiography (DSA) in the detection of secondary causes of intracerebral hemorrhage (ICH).
Between January 2001 and February 2007 there were 286 patients that had both CTA and DSA for intracranial hemorrhage of all types. Those with primarily subarachnoid hemorrhage or recent trauma were excluded. Fifty-five patients formed the study cohort. Three reviewers independently analyzed the CTAs in a blinded protocol and classified them based on presence or absence of a secondary etiology. Results were compared with the reference standard DSA and kappa values determined for interobserver variability.
The overall sensitivity, specificity, positive predictive value, negative predictive value and accuracy of CTA were 89%, 92%, 91%, 91% and 91%, respectively. Kappa value for interobserver agreement ranged from 0.78 to 0.89. Two of four dural arteriovenous fistulas (dAVF) were missed on CTA by all three reviewers.
CTA is nearly as effective as DSA at determining the cause of secondary intracerebral hemorrhage, but with a lower sensitivity for dAVFs. This supports the use of CTA as the first screening test in patients presenting with spontaneous ICH.