Carotid Intima-Media Thickness: Novel Loci, Sex-Specific Effects, and Genetic Correlations With Obesity and Glucometabolic Traits in UK Biobank.

OBJECTIVE: Atherosclerosis is the underlying cause of most cardiovascular disease, but mechanisms underlying atherosclerosis are incompletely understood. Ultrasound measurement of the carotid intima-media thickness (cIMT) can be used to measure vascular remodeling, which is indicative of atherosclerosis. Genome-wide association studies have identified many genetic loci associated with cIMT, but heterogeneity of measurements collected by many small cohorts have been a major limitation in these efforts. Here, we conducted genome-wide association analyses in UKB (UK Biobank; N=22 179), the largest single study with consistent cIMT measurements. Approach and Results: We used BOLT-LMM software to run linear regression of cIMT in UKB, adjusted for age, sex, and genotyping chip. In white British participants, we identified 5 novel loci associated with cIMT and replicated most previously reported loci. In the first sex-specific analyses of cIMT, we identified a locus on chromosome 5, associated with cIMT in women only and highlight VCAN as a good candidate gene at this locus. Genetic correlations with body mass index and glucometabolic traits were also observed. Two loci influenced risk of ischemic heart disease. CONCLUSIONS: These findings replicate previously reported associations, highlight novel biology, and provide new directions for investigating the sex differences observed in cardiovascular disease presentation and progression.

Dietary advice for people with schizophrenia.

BACKGROUND: People with serious mental illness have consistently higher levels of mortality and morbidity than the general population. They have greater levels of cardiovascular disease, metabolic disease, diabetes, and respiratory illness. Although genetics may have a role in the physical health problems of these people, lifestyle and environmental factors such as smoking, obesity, poor diet, and low levels of physical activity play a prominent part. OBJECTIVES: To review the effects of dietary advice for schizophrenia and schizophrenia-like psychosis. SEARCH METHODS: We searched the Cochrane Schizophrenia Group's Trials Register (September 09, 2013 and February 24, 2016). SELECTION CRITERIA: We planned to include all randomised clinical trials focusing on dietary advice versus standard care. DATA COLLECTION AND ANALYSIS: The review authors (RP, KTP) independently screened search results but did not identify any studies that fulfilled the review's criteria. MAIN RESULTS: We did not identify any studies that met our inclusion criteria. AUTHORS' CONCLUSIONS: Dietary advice has been shown to improve the dietary intake of the general population. Research is needed to determine whether dietary advice can have a similar benefit in people with serious mental illness.

Understanding the problems developing a healthy living programme in patients with serious mental illness: a qualitative study.

BACKGROUND: People with serious mental illness are at an increased risk of physical ill health. Mortality rates are around twice those of the general population with higher levels of cardiovascular disease, metabolic disease, diabetes, and respiratory illness. Although genetics may have a role in the physical health problems of these patients, lifestyle and environmental factors such as smoking, obesity, poor diet, and low levels of physical activity play a prominent part. METHODS: A qualitative grounded theory approach was used to understand the problems experienced by these individuals when asked to attend a healthy living programme. Three main areas were explored: the influence of potential barriers, health problems, and general attitudes towards healthy living. RESULTS: Thirteen patients were interviewed during the study. Many did not recall receiving an initial invitation letter to the programme. Several believed that there was no necessity to attend as they had already had recent routine health checks by their general practitioner. The patients' current level of mental and physical health was important with symptoms such as depression, anxiety or arthritis affecting interest in the programme. Patients described that they found smoking enjoyable or calming in its effect. Dietary intake was determined by taste or gaining pleasure in eating certain types of food. Several lessons were learnt during this research that may aid future research and practice. Participation seemed to be better if the approach was first made by the patient's own community keyworker. This contact may have provided a greater opportunity to explain the purpose and importance of the programme. Alternative appointments should be considered when certain patients are in better physical and mental health. Healthy living programmes need to be flexible and adaptive to individual patient needs. Assistance from their community worker may help engagement. Simple measures may improve participation and reduce potential barriers. CONCLUSION: These findings highlighted some of the problems encountered by patients when attempting to participate in a healthy living programme. These results may be useful when implementing future healthy living interventions for patients with serious mental disorders.

Exercise therapy in adults with serious mental illness: a systematic review and meta-analysis.

BACKGROUND: Individuals with serious mental illness are at a higher risk of physical ill health. Mortality rates are at least twice those of the general population with higher levels of cardiovascular disease, metabolic disease, diabetes, and respiratory illness. Although genetics may have a role in the physical health problems of these patients, lifestyle and environmental factors such as levels of smoking, obesity, poor diet, and low levels of physical activity also play a prominent part. METHODS: We conducted a systematic review and meta-analysis of randomised controlled trials comparing the effect of exercise interventions on individuals with serious mental illness.Searches were made in Ovid MEDLINE, Embase, CINAHL, PsycINFO, Biological Abstracts on Ovid, and The Cochrane Library (January 2009, repeated January 2013) through to February 2013. RESULTS: Eight RCTs were identified in the systematic search. Six compared exercise versus usual care. One study assessed the effect of a cycling programme versus muscle strengthening and toning exercises. The final study compared the effect of adding specific exercise advice and motivational skills to a simple walking programme. The review found that exercise improved levels of exercise activity (n = 13, standard mean difference [SMD] 1.81, CI 0.44 to 3.18, p = 0.01). No beneficial effect was found on negative (n = 84, SMD = -0.54, CI -1.79 to 0.71, p = 0.40) or positive symptoms of schizophrenia (n = 84, SMD = -1.66, CI -3.78 to 0.45, p = 0.12). No change was found on body mass index compared with usual care (n = 151, SMD = -0.24, CI -0.56 to 0.08, p = 0.14), or body weight (n = 77, SMD = 0.13, CI -0.32 to 0.58, p = 0.57). No beneficial effect was found on anxiety and depressive symptoms (n = 94, SMD = -0.26, CI -0.91 to 0.39, p = 0.43), or quality of life in respect of physical and mental domains. CONCLUSIONS: This systematic review showed that exercise therapies can lead to a modest increase in levels of exercise activity but overall there was no noticeable change for symptoms of mental health, body mass index, and body weight.

Living alone, loneliness and lack of emotional support as predictors of suicide and self-harm: A nine-year follow up of the UK Biobank cohort.

BACKGROUND: The association between loneliness and suicide is poorly understood. We investigated how living alone, loneliness and emotional support were related to suicide and self-harm in a longitudinal design. METHODS: Between 2006 and 2010 UK Biobank recruited and assessed in detail over 0.5 million people in middle age. Data were linked to prospective hospital admission and mortality records. Adjusted Cox regression models were used to investigate relationships between living arrangements, loneliness and emotional support, and both suicide and self-harm as outcomes. RESULTS: For men, both living alone (Hazard Ratio (HR) 2.16, 95%CI 1.51-3.09) and living with non-partners (HR 1.80, 95%CI 1.08-3.00) were associated with death by suicide, independently of loneliness, which had a modest relationship with suicide (HR 1.43, 95%CI 0.1.01-2.03). For women, there was no evidence that living arrangements, loneliness or emotional support were associated with death by suicide. Associations between living alone and self-harm were explained by health for women, and by health, loneliness and emotional support for men. In fully adjusted models, loneliness was associated with hospital admissions for self-harm in both women (HR 1.89, 95%CI 1.57-2.28) and men (HR 1.74, 95%CI 1.40-2.16). LIMITATIONS: Loneliness and emotional support were operationalized using single item measures. CONCLUSIONS: For men - but not for women - living alone or living with a non-partner increased the risk of suicide, a finding not explained by subjective loneliness. Overall, loneliness may be more important as a risk factor for self-harm than for suicide. Loneliness also appears to lessen the protective associations of cohabitation.

Mental health in UK Biobank - development, implementation and results from an online questionnaire completed by 157 366 participants: a reanalysis.

BACKGROUND: 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. AIMS: Describe the development, implementation and results of this questionnaire. METHOD: 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. RESULTS: 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. CONCLUSIONS: 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.

Pharmacological and behavioural interventions to promote smoking cessation in adults with schizophrenia and bipolar disorders: a systematic review and meta-analysis of randomised trials.

OBJECTIVE: Smoking in people with serious mental illness is a major public health problem and contributes to significant levels of morbidity and mortality. The aim of the review was to systematically examine the efficacy of methods used to aid smoking cessation in people with serious mental illness. METHOD: A systematic review and meta-analysis of randomised controlled trials to compare the effectiveness and safety of pharmacological and behavioural programmes for smoking cessation in people with serious mental illness. Electronic databases were searched for trials to July 2018. We used the Cochrane Collaboration's tool for assessing the risk of bias. RESULTS: Twenty-eight randomised controlled trials were identified. Varenicline increased the likelihood of smoking cessation at both 3 months (risk ratio (RR) 3.56, 95% CI 1.82 to 6.96, p=0.0002) and at 6 months (RR 3.69, 95% CI 1.08 to 12.60, p=0.04). Bupropion was effective at 3 months (RR 3.96, 95% CI 1.86 to 8.40, p=0.0003), especially at a dose of 300 mg/day, but there was no evidence of effect at 6 months (RR 2.22, 95% CI 0.52 to 9.47, p=0.28). In one small study, nicotine therapy proved effective at increasing smoking cessation up to a period of 3 months. Bupropion used in conjunction with nicotine replacement therapy showed more effect than single use. Behavioural and bespoke interventions showed little overall benefit. Side effects were found to be low. CONCLUSION: The new information of this review was the effectiveness of varenicline for smoking cessation at both 3 and 6 months and the lack of evidence to support the use of both bupropion and nicotine products for sustained abstinence longer than 3 months. Overall, the review found relatively few studies in this population.

Health screening, cardiometabolic disease and adverse health outcomes in individuals with severe mental illness.

BACKGROUND: Poor physical health in severe mental illness (SMI) remains a major issue for clinical practice. AIMS: To use electronic health records of routinely collected clinical data to determine levels of screening for cardiometabolic disease and adverse health outcomes in a large sample (n = 7718) of patients with SMI, predominantly schizophrenia and bipolar disorder. METHOD: We linked data from the Glasgow Psychosis Clinical Information System (PsyCIS) to morbidity records, routine blood results and prescribing data. RESULTS: There was no record of routine blood monitoring during the preceding 2 years for 16.9% of the cohort. However, monitoring was poorer for male patients, younger patients aged 16-44, those with schizophrenia, and for tests of cholesterol, triglyceride and glycosylated haemoglobin. We estimated that 8.0% of participants had diabetes and that lipids levels, and use of lipid-lowering medication, was generally high. CONCLUSIONS: Electronic record linkage identified poor health screening and adverse health outcomes in this vulnerable patient group. This approach can inform the design of future interventions and health policy.

Indicators of mental disorders in UK Biobank-A comparison of approaches.

OBJECTIVES: For many research cohorts, it is not practical to provide a "gold-standard" mental health diagnosis. It is therefore important for mental health research that potential alternative measures for ascertaining mental disorder status are understood. METHODS: Data from UK Biobank in those participants who had completed the online Mental Health Questionnaire (n = 157,363) were used to compare the classification of mental disorder by four methods: symptom-based outcome (self-complete based on diagnostic interviews), self-reported diagnosis, hospital data linkage, and self-report medication. RESULTS: Participants self-reporting any psychiatric diagnosis had elevated risk of any symptom-based outcome. Cohen's κ between self-reported diagnosis and symptom-based outcome was 0.46 for depression, 0.28 for bipolar affective disorder, and 0.24 for anxiety. There were small numbers of participants uniquely identified by hospital data linkage and medication. CONCLUSION: Our results confirm that ascertainment of mental disorder diagnosis in large cohorts such as UK Biobank is complex. There may not be one method of classification that is right for all circumstances, but an informed and transparent use of outcome measure(s) to suit each research question will maximise the potential of UK Biobank and other resources for mental health research.

Identification of novel genome-wide associations for suicidality in UK Biobank, genetic correlation with psychiatric disorders and polygenic association with completed suicide.

BACKGROUND: Suicide is a major issue for global public health. Suicidality describes a broad spectrum of thoughts and behaviours, some of which are common in the general population. Although suicide results from a complex interaction of multiple social and psychological factors, predisposition to suicidality is at least partly genetic. METHODS: Ordinal genome-wide association study of suicidality in the UK Biobank cohort comparing: 'no suicidality' controls (N = 83,557); 'thoughts that life was not worth living' (N = 21,063); 'ever contemplated self-harm' (N = 13,038); 'act of deliberate self-harm in the past' (N = 2498); and 'previous suicide attempt' (N = 2666). OUTCOMES: We identified three novel genome-wide significant loci for suicidality (on chromosomes nine, 11 and 13) and moderate-to-strong genetic correlations between suicidality and a range of psychiatric disorders, most notably depression (rg 0·81). INTERPRETATION: These findings provide new information about genetic variants relating to increased risk of suicidal thoughts and behaviours. Future work should assess the extent to which polygenic risk scores for suicidality, in combination with non-genetic risk factors, may be useful for stratified approaches to suicide prevention at a population level. FUND: UKRI Innovation-HDR-UK Fellowship (MR/S003061/1). MRC Mental Health Data Pathfinder Award (MC_PC_17217). MRC Doctoral Training Programme Studentship at the University of Glasgow (MR/K501335/1). MRC Doctoral Training Programme Studentship at the Universities of Glasgow and Edinburgh. UKRI Innovation Fellowship (MR/R024774/1).

Erratum: Mental health in UK Biobank: development, implementation and results from an online questionnaire completed by 157 366 participants - CORRIGENDUM.

[This corrects the article DOI: 10.1192/bjo.2018.12.].

Erratum: Mental health in UK Biobank: development, implementation and results from an online questionnaire completed by 157 366 participants - CORRIGENDUM.

[This corrects the article DOI: 10.1192/bjo.2018.12.].

Mental health in UK Biobank: development, implementation and results from an online questionnaire completed by 157 366 participants.

BACKGROUND: UK Biobank is a well-characterised cohort of over 500 000 participants that offers unique opportunities to investigate multiple diseases and risk factors. AIMS: An online mental health questionnaire completed by UK Biobank participants was expected to expand the potential for research into mental disorders. METHOD: 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. RESULTS: 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. CONCLUSIONS: 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.