Epidemiological studies have previously shown a link between cardiometabolic disease and severe mental illness. The extent and mechanisms behind this link are poorly understood currently but links to impairments in the stress response and cortisol regulation have been thought to play a significant role. BMAL1 is a circadian rhythm regulation gene found on chromosome 11 which has been associated with a variety of pro-inflammatory states as well as conditions such as depression, schizophrenia, type 2 diabetes mellitus and myocardial infarction. Our study aimed to investigate the genetic structure of the BMAL1 gene locus and its associations with both cardiometabolic and psychiatric traits and conditions.

We used genetic data from the UK Biobank which recruited ~500,000 participants. Of these we used a population of ~430,000 self-reported white British participants and data from a variety of questionnaires and investigations looking at severe mental illness and cardiometabolic traits. We performed association analyses using Plink 1.07 with Bonferroni correction being performed for multiple testing using a number of genetic variants. Our threshold for significance was defined as a p-value < 5.35 × 10−5. Conditional analysis was then performed to identify if there were multiple independent signals for each phenotype.

BMAL1 variants were associated with BMI, diastolic, systolic blood pressure, waist-hip ratio and neuroticism score, and risk of anhedonia, major depressive disorder and risk-taking behaviour. Multiple significant independent signals were identified for BMI and waist-hip ratio. Linkage disequilibrium (LD) analysis showed significant coinheritance of specific traits which could suggest a role for BMAL1 and the encoded protein as a link between cardiometabolic and mental health traits.

This is the first study that systematically investigated associations between the BMAL1 locus across a variety of different mental and cardiometabolic phenotypes in a population-level cohort. Our study has shown that there is a link between the BMAL1 locus and both cardiometabolic and mental health phenotypes. Further research is required to investigate the exact biological mechanism by which BMAL1 connects severe mental illness and cardiometabolic disease.

Mobile phone reminding apps can be used by people with acquired brain injury (ABI) to compensate for their memory impairments. However off-the-shelf apps may be difficult to use. ApplTree has been developed to be accessible to this group, compared to off-the-shelf reminding apps such as Google Calendar. This pilot feasibility trial aimed to establish the feasibility of running (and issues that should be addressed to complete) a randomised controlled trial comparing ApplTree to Google Calendar in an ABI community treatment setting.

Adults with self or other reported memory difficulty after an ABI were enrolled (n=39). Those who completed the baseline phase were randomised (n=29) and randomly allocated to the Google Calendar or ApplTree intervention. They were shown a 30 minute video tutorial of the app and an assessment on their ability to use it. Timely completion of everyday memory tasks were measured for a 3 week pre-intervention baseline and 3 week post-intervention follow-up phase. Participants also completed neuropsychological tests assessing memory, attention and executive function and gave qualitative feedback on the app and their experience in the trial.

Recruitment rate was 58% of the target (29 were randomised, n=50 was the target in 2 years). Retention rate was 65.5% and adherence rate was 57.9%. While the feasibility trial was not powered to calculate efficacy, there was a 13% increase in everyday memory tasks completed on time for those in the ApplTree group (n=10) compared to baseline and no change for the Google Calendar group (n=9). Feasibility results indicate 72 participants would need to fully complete a trial to detect the minimum clinically important difference (12.5% increase in successful performance of everyday memory tasks) in the efficacy of ApplTree compared to Google Calendar, should such a difference exist.

The challenges with recruitment of people receiving community care for ABI are highlighted in this trial and discussed along with the impact of the Covid-19 pandemic. Methodological considerations for researchers or clinicians looking to measure everyday memory ability are discussed. The majority (19 of 21) of participants who were given an app were capable of learning to use it during an hour-long session. This indicates it is a feasible intervention that community ABI services could offer. Participant feedback highlighted the merits of design features implemented in ApplTree that can improve the uptake and utility of reminding apps.

Health and social care workers (HSCWs) are at risk of experiencing adverse mental health outcomes (e.g. higher levels of anxiety and depression) because of the COVID-19 pandemic. This can have a detrimental effect on quality of care, the national response to the pandemic and its aftermath.

A longitudinal design provided follow-up evidence on the mental health (changes in prevalence of disease over time) of NHS staff working at a remote health board in Scotland during the COVID-19 pandemic, and investigated the determinants of mental health outcomes over time.

A two-wave longitudinal study was conducted from July to September 2020. Participants self-reported levels of depression (Patient Health Questionnaire-9), anxiety (Generalised Anxiety Disorder-7) and mental well-being (Warwick-Edinburgh Mental Well-being Scale) at baseline and 1.5 months later.

The analytic sample of 169 participants, working in community (43%) and hospital (44%) settings, reported substantial levels of depression and anxiety, and low mental well-being at baseline (depression, 30.8%; anxiety, 20.1%; well-being, 31.9%). Although mental health remained mostly constant over time, the proportion of participants meeting the threshold for anxiety increased to 27.2% at follow-up. Multivariable modelling indicated that working with, and disruption because of, COVID-19 were associated with adverse mental health changes over time.

HSCWs working in a remote area with low COVID-19 prevalence reported substantial levels of anxiety and depression, similar to those working in areas with high COVID-19 prevalence. Efforts to support HSCW mental health must remain a priority, and should minimise the adverse effects of working with, and disruption caused by, the COVID-19 pandemic.

To propose a set of internationally harmonized procedures and methods for assessing neurocognitive functions, smell, taste, mental, and psychosocial health, and other factors in adults formally diagnosed with COVID-19 (confirmed as SARS-CoV-2 + WHO definition).

We formed an international and cross-disciplinary NeuroCOVID Neuropsychology Taskforce in April 2020. Seven criteria were used to guide the selection of the recommendations’ methods and procedures: (i) Relevance to all COVID-19 illness stages and longitudinal study design; (ii) Standard, cross-culturally valid or widely available instruments; (iii) Coverage of both direct and indirect causes of COVID-19-associated neurological and psychiatric symptoms; (iv) Control of factors specifically pertinent to COVID-19 that may affect neuropsychological performance; (v) Flexibility of administration (telehealth, computerized, remote/online, face to face); (vi) Harmonization for facilitating international research; (vii) Ease of translation to clinical practice.

The three proposed levels of harmonization include a screening strategy with telehealth option, a medium-size computerized assessment with an online/remote option, and a comprehensive evaluation with flexible administration. The context in which each harmonization level might be used is described. Issues of assessment timelines, guidance for home/remote assessment to support data fidelity and telehealth considerations, cross-cultural adequacy, norms, and impairment definitions are also described.

The proposed recommendations provide rationale and methodological guidance for neuropsychological research studies and clinical assessment in adults with COVID-19. We expect that the use of the recommendations will facilitate data harmonization and global research. Research implementing the recommendations will be crucial to determine their acceptability, usability, and validity.

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.

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 84,268 UK Biobank 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.

Increased serum CRP was significantly associated with mood disorder history (Kruskal–Wallis H = 196.06, p < 0.001, η2 = 0.002) but increased polygenic risk for CRP was not (F = 0.668, p = 0.648, η2 < 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.

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.

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.

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.

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.

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.

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.

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.

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.

I.J.D. is a UK Biobank participant. J.P.P. is a member of the UK Biobank Steering Committee.

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.

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.

The relative contribution of demographic, lifestyle and medication factors to the association between affective disorders and cardiometabolic diseases is poorly understood.

To assess the relationship between cardiometabolic disease and features of depresion and bipolar disorder within a large population sample.

Cross-sectional study of 145 991 UK Biobank participants: multivariate analyses of associations between features of depression or bipolar disorder and five cardiometabolic outcomes, adjusting for confounding factors.

There were significant associations between mood disorder features and ‘any cardiovascular disease’ (depression odds ratio (OR) = 1.15, 95% CI 1.12–1.19; bipolar OR = 1.28, 95% CI 1.14–1.43) and with hypertension (depression OR = 1.15, 95% CI 1.13–1.18; bipolar OR = 1.26, 95% CI 1.12–1.42). Individuals with features of mood disorder taking psychotropic medication were significantly more likely than controls not on psychotropics to report myocardial infarction (depression OR = 1.47, 95% CI 1.24–1.73; bipolar OR = 2.23, 95% CI 1.53–3.57) and stroke (depression OR = 2.46, 95% CI 2.10–2.80; bipolar OR = 2.31, 95% CI 1.39–3.85).

Associations between features of depression or bipolar disorder and cardiovascular disease outcomes were statistically independent of demographic, lifestyle and medication confounders. Psychotropic medication may also be a risk factor for cardiometabolic disease in individuals without a clear history of mood disorder.

There is controversy about whether late-onset schizophrenia is a precursor of cognitive decline.

To examine the long-term outcome of a group of patients with late-onset schizophrenia.

Patients with onset of DSM–III–R schizophrenia at age 50 years or over, but without dementia, and a healthy control group were assessed at baseline (n=27 and n=34, respectively), after 1 year and after 5 years (n=19 and n=24, respectively) on measures of psychopathology, cognition and general functioning, and compared on rates of decline and incidence of dementia.

Nine patients with late-onset schizophrenia and none of the control group were found to have dementia (5 Alzheimer type, 1 vascular, 3 dementia of unknown type) at 5-year follow-up. There appeared to be a subgroup of late-onset schizophrenia patients without signs of dementia at baseline or at 1 year follow-up who subsequently declined.

Late-onset schizophrenia may be a prodrome of Alzheimer-type dementia. More longitudinal studies are required to determine its nosological status.