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Masao Iwagami,1 Kathryn E Mansfield,1 Joseph F Hayes,2 Kate Walters,3 David PJ Osborn,2,4 Liam Smeeth,1 Dorothea Nitsch,1 Laurie A Tomlinson1 1Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK; 2Division of Psychiatry, University College London, London, UK; 3Department of Primary Care and Population Health, University College London, London, UK; 4Camden and Islington NHS Foundation Trust, London, UK Objective: We investigated the burden of chronic kidney disease (CKD) among patients with severe mental illness (SMI). Methods: We identified patients with SMI among all those aged 25–74 registered in the UK Clinical Practice Research Datalink as on March 31, 2014. We compared the prevalence of CKD (two measurements of estimated glomerular filtration rate

Background and Methods: Psychiatric research can occasionally present particular ethical dilemmas, but it is not clear what kind of problems local research ethics committees (LRECs) actually experience in this field. We aimed to assess the type of problems that committees encounter with psychiatric research, using a postal survey of 211 LRECs.Results: One hundred and seven (51%) of those written to replied within the time limit. Twenty eight (26%) experienced few problems with psychiatric applications. Twenty six (24%) emphasised the value of a psychiatric expert on the committee. The most common issues raised were informed consent (n=64, 60%) and confidentiality (n=17, 16%). The use of placebos (and washout periods) (n=18, 17%), the validity of psychiatric questionnaires (n=16, 15%) and overuse of psychiatric "jargon" (n=14, 13%) in psychiatric applications also raised concern.Conclusions: Our results suggest that LRECs have specific concerns regarding methodology, consent, and confidentiality in psychiatric research, and that they find psychiatric input invaluable. [ABSTRACT FROM AUTHOR]

Background: There is limited and conflicting evidence on the comparative cardiometabolic safety and effectiveness of aripiprazole in the management of severe mental illness. We investigated the hypothesis that aripiprazole has a favourable cardiometabolic profile, but similar effectiveness when compared to olanzapine, quetiapine, and risperidone., Methods and Findings: We conducted an observational emulation of a head-to-head trial of aripiprazole versus olanzapine, quetiapine, and risperidone in UK primary care using data from the Clinical Practice Research Datalink. We included adults diagnosed with severe mental illness (i.e., bipolar disorder, schizophrenia, and other non-organic psychoses) who were prescribed a new antipsychotic between 2005 and 2017, with a 2-year follow-up to 2019. The primary outcome was total cholesterol at 1 year (cardiometabolic safety). The main secondary outcome was psychiatric hospitalisation (effectiveness). Other outcomes included body weight, blood pressure, all-cause discontinuation, and mortality. Analyses adjusted for baseline confounders, including sociodemographics, diagnoses, concomitant medications, and cardiometabolic parameters. We included 26,537 patients (aripiprazole, n = 3,573, olanzapine, n = 8,554, quetiapine, n = 8,289, risperidone, n = 6,121). Median (IQR) age was 53 (42-67) years, 55.4% were female, 82.3% White, and 18.0% were diagnosed with schizophrenia. Patients prescribed aripiprazole had similar total cholesterol levels after 1 year to those prescribed olanzapine (adjusted mean difference [aMD], -0.03, 95% CI, -0.09 to 0.02, p = 0.261), quetiapine (aMD, -0.03, 95% CI, -0.09 to 0.03, p = 0.324), and risperidone (aMD, -0.01, 95% CI, -0.08 to 0.05, p = 0.707). However, there was evidence that patients prescribed aripiprazole had better outcomes on other cardiometabolic parameters, such as body weight and blood pressure, especially compared to olanzapine. After additional adjustment for prior hospitalisation, patients prescribed aripiprazole had similar rates of psychiatric hospitalisation as those prescribed olanzapine (adjusted hazard ratio [aHR], 0.91, 95% CI, 0.82 to 1.01, p = 0.078), quetiapine (aHR, 0.94, 95% CI, 0.85 to 1.04, p = 0.230), or risperidone (aHR, 1.01, 95% CI, 0.91 to 1.12, p = 0.854)., Conclusions: Data from our large, powered, diverse, real-world target trial emulation sample, followed over 2 years, suggest that adults diagnosed with severe mental illness prescribed aripiprazole have similar total cholesterol 1 year after first prescription compared to those prescribed olanzapine, quetiapine, and risperidone. However, patients prescribed aripiprazole had better outcomes on some other cardiometabolic parameters, and there was little evidence of differences in effectiveness. Our findings inform a common clinical dilemma and contribute to the evidence base for real-world clinical decision-making on antipsychotic choice for patients diagnosed with severe mental illness., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: JFH has received consultancy fees from Wellcome Trust and funding grants from juli Health unrelated to the results of the current study. All other authors declare no competing interests., (Copyright: © 2025 Richards-Belle et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: People with severe mental illness (SMI) are at increased risk of cardiovascular disease (CVD), and initiatives for CVD risk factor screening in the UK have not reduced disparities., Objectives: To describe the annual screening prevalence for CVD risk factors in people with SMI from April 2000 to March 2018, and to identify factors associated with receiving no screening and regular screening., Methods: We identified adults with a diagnosis of SMI (schizophrenia, bipolar disorder or 'other psychosis') from UK primary care records in Clinical Practice Research Datalink. We calculated the annual prevalence of screening for blood pressure, cholesterol, glucose, body mass index, alcohol consumption and smoking status using multinomial logistic regression to identify factors associated with receiving no screening and complete screening., Results: Of 216 136 patients with SMI, 55% received screening for all six CVD risk factors at least once during follow-up and 35% received all six within a 1-month period. Our findings suggest that patient characteristics and financial incentivisation influence screening prevalence of individual CVD risk factors, the likelihood of receiving screening for all six CVD risk factors annually and risk of receiving no screening., Conclusions: The low proportion of people with SMI receiving regular comprehensive CVD risk factor screening is concerning. Screening needs to be embedded as part of broad physical health checks to ensure the health needs of people with SMI are being met. If we are to improve cardiovascular health, interventions are needed where risk of receiving no screening or not receiving regular screening is highest., Competing Interests: Competing interests: JFH has received consultancy fees from juli Health and Wellcome. He is a co-founder and shareholder of juli Health. juli Health has a patent pending. RS declares research support received in the last 3 years from GSK and Takeda., (© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY. Published by BMJ Group.)

Purpose: In 2012, the UK government announced legislation changes and heightened immigration controls designed to create a 'hostile environment for illegal migration.' We measured changes in psychological distress among people from minoritised ethnic groups compared to White British controls before and throughout the implementation of these policies., Methods: We used the UK Household Longitudinal Survey to estimate difference-in-difference models for six ethnic groups (Bangladeshi, African, Caribbean, Indian, Pakistani, and White British) in three eras: pre-policy (2009-2012); (2) transition (2012-2016); and (3) ongoing policy (2016-2020). We calculated the adjusted marginal mean psychological distress score at each era using the 12-item General Health Questionnaire (GHQ)., Results: In the pre-policy era, we found higher psychological distress for the Pakistani, Bangladeshi, and Caribbean groups compared to the White British group. We observed patterns consistent with increasing psychological distress during the transition era for the Pakistani and Bangladeshi groups, with further increases in the ongoing era for the Bangladeshi group. Levels of psychological distress the Indian and African groups were similar to the White British group in the pre-policy era and decreased over successive eras. A small decrease was observed in the Caribbean group across policy eras, while levels remained stable in the White British group., Conclusion: We found evidence that psychological distress increased among Pakistani and Bangladeshi individuals following the introduction of hostile environment policies but did not detect increased distress in other ethnic groups. This finding underscores the importance of disaggregating analyses by ethnic group to capture the distinct experiences., Competing Interests: Declarations. Conflict of interests: The authors have no conflicts of interest to declare., (© 2024. The Author(s).)

Background: Contemporary data relating to antipsychotic prescribing in UK primary care for patients diagnosed with severe mental illness (SMI) are lacking., Aims: To describe contemporary patterns of antipsychotic prescribing in UK primary care for patients diagnosed with SMI., Method: Cohort study of patients with an SMI diagnosis (i.e. schizophrenia, bipolar disorder, other non-organic psychoses) first recorded in primary care between 2000 and 2017 derived from Clinical Practice Research Datalink. Patients were considered exposed to antipsychotics if prescribed at least one antipsychotic in primary care between 2000 and 2019. We compared characteristics of patients prescribed and not prescribed antipsychotics; calculated annual prevalence rates for antipsychotic prescribing; and computed average daily antipsychotic doses stratified by patient characteristics., Results: Of 309 378 patients first diagnosed with an SMI in primary care between 2000 and 2017, 212,618 (68.7%) were prescribed an antipsychotic between 2000 and 2019. Antipsychotic prescribing prevalence was 426 (95% CI, 420-433) per 1000 patients in the year 2000, reaching a peak of 550 (547-553) in 2016, decreasing to 470 (468-473) in 2019. The proportion prescribed antipsychotics was higher among patients diagnosed with schizophrenia (81.0%) than with bipolar disorder (64.6%) and other non-organic psychoses (65.7%). Olanzapine, quetiapine, risperidone and aripiprazole accounted for 78.8% of all antipsychotic prescriptions. Higher mean olanzapine equivalent total daily doses were prescribed to patients with the following characteristics: schizophrenia diagnosis, ethnic minority status, male gender, younger age and greater relative deprivation., Conclusions: Antipsychotic prescribing is dominated by olanzapine, quetiapine, risperidone and aripiprazole. We identified potential disparities in both the receipt and prescribed doses of antipsychotics across subgroups. To inform efforts to optimise prescribing and ensure equity of care, further research is needed to understand why certain groups are prescribed higher doses and are more likely to be treated with long-acting injectable antipsychotics compared with others.

Background: Poor social connectedness has been identified as a risk factor for poor mental health but there is a lack of standardisation in how it is measured. This systematic review aimed to identify suitable measures of social connectedness for use in UK adult general populations., Methods: Searches were undertaken in two stages to identify: (1) measures of social connectedness from review articles and grey literature and (2) studies reporting on the psychometric properties of the identified measures. Grey literature and five databases were searched: MEDLINE, Embase and PsycINFO; CINAHL and Web of Science. Studies based on UK adult general populations (16-65 years) or other English language speaking countries with similar cultures (US, Canada, Ireland, Australia and New Zealand) were included. Psychometric evidence was extracted relating to six general domains: conceptual model, content validity, reliability, construct validity, scoring and interpretability, and respondent burden and presentation. A narrative synthesis summarised these psychometric properties., Results: Stage (1) 2,396 studies were retrieved and, 24 possible measures of social connectedness were identified; stage (2) 6,218 studies were identified reporting on psychometrics of identified measures and 22 studies were included. These studies provided psychometric evidence for 10 measures, and we did not find psychometric studies for the other identified measures. Six measures (6/10, 60%) reported assessing loneliness and four (4/10, 40%) reported assessing social support but there was a degree of overlap between the assessments of each concept. There was good evidence of reliability across measures, 90% (9/10) had adequate internal consistency, but evidence of content validity was only available for one scale. Five measures (5/10, 50%) reported on at least half of the psychometric criteria, and these were: UCLA-3 (for loneliness), and MSPSS, F-SozU K-6, SPS-10 and SPS-5 (for social support)., Conclusions: This review identified ten social connectedness measures, and identified UCLA-3, MSPSS, F-SozUK-6, SPS-10, and SPS-5 as having the most robust psychometric properties for the UK adult population. Further testing is required to establish content validity, and to clarify the definition and conceptualisation of social connectedness, to enable standardisation in the approach to measuring social connectedness., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Optimising maintenance drug treatment selection for people with bipolar disorder is challenging. There is some evidence that clinical and demographic features may predict response to lithium. However, attempts to personalise treatment choice have been limited., Method: We aimed to determine if machine learning methods applied to electronic health records could predict differential response to lithium or olanzapine. From electronic United Kingdom primary care records, we extracted a cohort of individuals prescribed either lithium (19,106 individuals) or olanzapine (12,412) monotherapy. Machine learning models were used to predict successful monotherapy maintenance treatment, using 113 clinical and demographic variables, 8,017 (41.96%) lithium responders and 3,831 (30.87%) olanzapine responders., Results: We found a quantitative structural difference in that lithium maintenance responders were weakly predictable in our holdout sample, consisting of the 5% of patients with the most recent exposure. Age at first diagnosis, age at first treatment and the time between these were the most important variables in all models., Discussion: Even if we failed to predict successful monotherapy olanzapine treatment, and so to definitively separate lithium vs . olanzapine responders, the characterization of the two groups may be used for classification by proxy. This can, in turn, be useful for establishing maintenance therapy. The further exploration of machine learning methods on EHR data for drug treatment selection could in the future play a role for clinical decision support. Signals in the data encourage further experiments with larger datasets to definitively separate lithium vs . olanzapine responders., Competing Interests: Joseph F. Hayes has received consultancy fees from juli Health and Wellcome Trust. No other authors declare competing interests., (© 2024 Hayes et al.)

Lithium is considered to be the most effective mood stabilizer for bipolar disorder. Evolving evidence suggested lithium can also regulate bone metabolism which may reduce the risk of fractures. While there are concerns about fractures for antipsychotics and mood stabilizing antiepileptics, very little is known about the overall risk of fractures associated with specific treatments. This study aimed to compare the risk of fractures in patients with bipolar disorder prescribed lithium, antipsychotics or mood stabilizing antiepileptics (valproate, lamotrigine, carbamazepine). Among 40,697 patients with bipolar disorder from 1993 to 2019 identified from a primary care electronic health record database in the UK, 13,385 were new users of mood stabilizing agents (lithium:2339; non-lithium: 11,046). Lithium was associated with a lower risk of fractures compared with non-lithium treatments (HR 0.66, 95 % CI 0.44-0.98). The results were similar when comparing lithium with prolactin raising and sparing antipsychotics, and individual antiepileptics. Lithium use may lower fracture risk, a benefit that is particularly relevant for patients with serious mental illness who are more prone to falls due to their behaviors. Our findings could help inform better treatment decisions for bipolar disorder, and lithium's potential to prevent fractures should be considered for patients at high risk of fractures., Competing Interests: Declaration of competing interest Esther W. Chan has received grants from Research Grants Council (RGC, Hong Kong), Research Fund Secretariat of the Food and Health Bureau, National Natural Science Fund of China, Bayer, Bristol-Myers Squibb, Pfizer, Janssen, Novartis, Amgen, AstraZeneca, Takeda, the RGA Reinsurance Company, Narcotics Division of the Security Bureau of the Hong Kong Special Administrative Region, the National Health and Medical Research Council Australia; consulting fees from AstraZeneca, Pfizer and Novartis; and honorarium from the Hospital Authority Hong Kong, outside the submitted work. Joseph F. Hayes has received consultancy fees from Wellcome Trust and juli Health. Kenneth K.C. Man received the CW Maplethorpe Fellowship, grants from the National Institute for Health Research (United Kingdom), the European Union Horizon 2020 Framework, Innovation and Technology Commission of the Hong Kong Special Administration Region Government, and Hong Kong Research Grant Council and personal fees from IQVIA Holdings, Inc., unrelated to this work. Ian C.K.Wong received research grants from Amgen, Janssen, GSK, Novartis, Pfizer, Bayer and Bristol-Myers Squibb and Takeda, Institute for Health Research in England, European Commission, National Health and Medical Research Council in Australia, The European Union's Seventh Framework Programme for research, technological development, Research Grants Council Hong Kong and Health and Medical Research Fund Hong Kong; consulting fee from IQVIA and WHO; payment for expert testimony for Appeal Court in Hong Kong; serves on advisory committees for Member of Pharmacy and Poisons Board; Member of the Expert Committee on Clinical Events Assessment Following COVID-19 Immunization; Member of the Advisory Panel on COVID-19 Vaccines of the Hong Kong Government; is the non-executive director of Jacobson Medical in Hong Kong; is the Founder and Director of Therakind Limited (UK), Advance Data Analytics for Medical Science (ADAMS) Limited (HK), Asia Medicine Regulatory Affairs (AMERA) Services Limited and OCUS Innovation Limited (HK, Ireland and UK). Ching-Lung Cheung received research grants and the honorarium from Amgen, research grant support from HMRF, and the honorarium from Abbott. Wallis C.Y. Lau reports grant from Diabetes UK, AIR@InnoHK administered by Innovation and Technology Commission, outside the submitted work. Vanessa W.S. Ng, Miriam T.Y. Leung, and David P.J. Osborn declare no conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Aims: Population-wide restrictions during the COVID-19 pandemic may create barriers to mental health diagnosis. This study aims to examine changes in the number of incident cases and the incidence rates of mental health diagnoses during the COVID-19 pandemic., Methods: By using electronic health records from France, Germany, Italy, South Korea and the UK and claims data from the US, this study conducted interrupted time-series analyses to compare the monthly incident cases and the incidence of depressive disorders, anxiety disorders, alcohol misuse or dependence, substance misuse or dependence, bipolar disorders, personality disorders and psychoses diagnoses before (January 2017 to February 2020) and after (April 2020 to the latest available date of each database [up to November 2021]) the introduction of COVID-related restrictions., Results: A total of 629,712,954 individuals were enrolled across nine databases. Following the introduction of restrictions, an immediate decline was observed in the number of incident cases of all mental health diagnoses in the US (rate ratios (RRs) ranged from 0.005 to 0.677) and in the incidence of all conditions in France, Germany, Italy and the US (RRs ranged from 0.002 to 0.422). In the UK, significant reductions were only observed in common mental illnesses. The number of incident cases and the incidence began to return to or exceed pre-pandemic levels in most countries from mid-2020 through 2021., Conclusions: Healthcare providers should be prepared to deliver service adaptations to mitigate burdens directly or indirectly caused by delays in the diagnosis and treatment of mental health conditions.

Background: The co-occurrence of stroke and psychosis is a serious neuropsychiatric condition but little is known about the course of this comorbidity. We aimed to estimate longitudinal associations between stroke and psychosis over 10 years., Methods: A 10-year population-based study using data from the English Longitudinal Study of Ageing. A structured health assessment recorded (i) first-occurrence stroke and (ii) psychosis, at each wave. Each were considered exposures and outcomes in separate analyses. Logistic and Cox proportional hazards regression and Kaplan-Meier methods were used. Models were adjusted for demographic and health behaviour covariates, with missing covariates imputed using random forest multiple imputation., Results: Of 19 808 participants, 24 reported both stroke and psychosis (median Wave 1 age 63, 71% female, 50% lowest quintile of net financial wealth) at any point during follow-up. By 10 years, the probability of an incident first stroke in participants with psychosis was 21.4% [95% confidence interval (CI) 12.1-29.6] compared to 8.3% (95% CI 7.8-8.8) in those without psychosis (absolute difference: 13.1%; 95% CI 20.8-4.3, log rank p < 0.001; fully-adjusted hazard ratio (HR): 3.57; 95% CI 2.18-5.84). The probability of reporting incident psychosis in participants with stroke was 2.3% (95% CI 1.4-3.2) compared to 0.9% (95% CI 0.7-1.1) in those without (absolute difference: 1.4%; 95% CI 0.7-2.1, log rank p < 0.001; fully-adjusted HR: 4.98; 95% CI 2.55-9.72)., Conclusions: Stroke is an independent predictor of psychosis (and vice versa), after adjustment for potential confounders.

Background: People with severe mental illness (SMI) have more physical health conditions than the general population, resulting in higher rates of hospitalisations and mortality. In this study, we aimed to determine the rate of emergency and planned physical health hospitalisations in those with SMI, compared to matched comparators, and to investigate how these rates differ by SMI diagnosis., Methods: We used Clinical Practice Research DataLink Gold and Aurum databases to identify 20,668 patients in England diagnosed with SMI between January 2000 and March 2016, with linked hospital records in Hospital Episode Statistics. Patients were matched with up to four patients without SMI. Primary outcomes were emergency and planned physical health admissions. Avoidable (ambulatory care sensitive) admissions and emergency admissions for accidents, injuries and substance misuse were secondary outcomes. We performed negative binomial regression, adjusted for clinical and demographic variables, stratified by SMI diagnosis., Results: Emergency physical health (aIRR:2.33; 95% CI 2.22-2.46) and avoidable (aIRR:2.88; 95% CI 2.60-3.19) admissions were higher in patients with SMI than comparators. Emergency admission rates did not differ by SMI diagnosis. Planned physical health admissions were lower in schizophrenia (aIRR:0.80; 95% CI 0.72-0.90) and higher in bipolar disorder (aIRR:1.33; 95% CI 1.24-1.43). Accident, injury and substance misuse emergency admissions were particularly high in the year after SMI diagnosis (aIRR: 6.18; 95% CI 5.46-6.98)., Conclusion: We found twice the incidence of emergency physical health admissions in patients with SMI compared to those without SMI. Avoidable admissions were particularly elevated, suggesting interventions in community settings could reduce hospitalisations. Importantly, we found underutilisation of planned inpatient care in patients with schizophrenia. Interventions are required to ensure appropriate healthcare use, and optimal diagnosis and treatment of physical health conditions in people with SMI, to reduce the mortality gap due to physical illness.

Recent studies raised concerns about the increasing use of gabapentinoids in different countries. With their potential for misuse and addiction, understanding the global consumption of gabapentinoids will offer us a platform to examine the need for any interventional policies. This longitudinal trend study utilised pharmaceutical sales data from 65 countries and regions across the world to evaluate the global trends in gabapentinoid consumption between 2008-2018. The multinational average annual percentage change of gabapentinoid consumption was +17.20%, increased from 4.17 defined daily dose per ten thousand inhabitants per day (DDD/TID) in 2008 to 18.26 DDD/TID in 2018. High-income countries had the highest pooled gabapentinoid consumption rate (39.92 DDD/TID) in 2018, which was more than six times higher than the lower-middle income countries (6.11 DDD/TID). The study shows that despite differences in healthcare system and culture, a consistent increase in gabapentinoid consumption is observed worldwide, with high-income countries remaining the largest consumers., (© 2023. Springer Nature Limited.)

Background: Patients with bipolar disorder (BPD) are prone to engage in risk-taking behaviours and self-harm, contributing to higher risk of traumatic injuries requiring medical attention at the emergency room (ER).We hypothesize that pharmacological treatment of BPD could reduce the risk of traumatic injuries by alleviating symptoms but evidence remains unclear. This study aimed to examine the association between pharmacological treatment and the risk of ER admissions due to traumatic injuries., Methods: Individuals with BPD who received mood stabilizers and/or antipsychotics were identified using a population-based electronic healthcare records database in Hong Kong (2001-2019). A self-controlled case series design was applied to control for time-invariant confounders., Results: A total of 5040 out of 14 021 adults with BPD who received pharmacological treatment and had incident ER admissions due to traumatic injuries from 2001 to 2019 were included. An increased risk of traumatic injuries was found 30 days before treatment [incidence rate ratio (IRR) 4.44 (3.71-5.31), p < 0.0001]. After treatment initiation, the risk remained increased with a smaller magnitude, before returning to baseline [IRR 0.97 (0.88-1.06), p = 0.50] during maintenance treatment. The direct comparison of the risk during treatment to that before and after treatment showed a significant decrease. After treatment cessation, the risk was increased [IRR 1.34 (1.09-1.66), p = 0.006]., Conclusions: This study supports the hypothesis that pharmacological treatment of BPD was associated with a lower risk of ER admissions due to traumatic injuries but an increased risk after treatment cessation. Close monitoring of symptoms relapse is recommended to clinicians and patients if treatment cessation is warranted.

Background: Antipsychotic polypharmacy (APP) occurs commonly but it is unclear whether it is associated with an increased risk of adverse drug reactions (ADRs). Electronic health records (EHRs) offer an opportunity to examine APP using real-world data. In this study, we use EHR data to identify periods when patients were prescribed 2 + antipsychotics and compare these with periods of antipsychotic monotherapy. To determine the relationship between APP and subsequent instances of ADRs: QT interval prolongation, hyperprolactinaemia, and increased body weight [body mass index (BMI) ⩾ 25]., Methods: We extracted anonymised EHR data. Patients aged 16 + receiving antipsychotic medication at Camden & Islington NHS Foundation Trust between 1 January 2008 and 31 December 2018 were included. Multilevel mixed-effects logistic regression models were used to elucidate the relationship between APP and the subsequent presence of QT interval prolongation, hyperprolactinaemia, and/or increased BMI following a period of APP within 7, 30, or 180 days respectively., Results: We identified 35 409 observations of antipsychotic prescribing among 13 391 patients. Compared with antipsychotic monotherapy, APP was associated with a subsequent increased risk of hyperprolactinaemia (adjusted odds ratio 2.46; 95% CI 1.87-3.24) and of registering a BMI > 25 (adjusted odds ratio 1.75; 95% CI 1.33-2.31) in the period following the APP prescribing., Conclusions: Our observations suggest that APP should be carefully managed with attention to hyperprolactinaemia and obesity.

Bipolar disorder (BPD) is associated with high rates of suicide attempts but the anti-suicidal effect of mood stabilizing agents remains unclear. This study aimed to examine the association between mood stabilizing agents (lithium, valproate, lamotrigine, carbamazepine or antipsychotics) and risk of suicide attempts in patients with BPD using self-controlled case series study design. Among 14,087 patients with BPD who received mood stabilizing agents from 2001 to 2020 in Hong Kong, 1316 patients had at least one suicide attempts during the observation period. An increased risk of suicide attempts was observed 14 days before treatment initiation compared to non-exposed period. Following treatment initiation, an increased risk with smaller magnitude was found with the use of mood stabilizing agents. A lower risk was observed with lithium and antiepileptics while the risk remained attenuated with decreasing magnitude with antipsychotics. During 30-day post-treatment period, the risk was elevated. Therefore, this study suggests that use of mood stabilizing agents is not causally associated with an increased risk of suicide attempts. Indeed, there are potential protective effects of lithium and antiepileptics against suicide attempts. Assiduous monitoring of symptoms relapse and warning signs of suicide should be part of the management plan and discussed between clinicians, caregivers and patients., Competing Interests: Declaration of Competing Interest Esther W. Chan has received grants from Research Grants Council (RGC, Hong Kong), Research Fund Secretariat of the Food and Health Bureau, National Natural Science Fund of China, Bayer, Bristol-Myers Squibb, Pfizer, Janssen, Novartis, Amgen, AstraZeneca, Takeda, the RGA Reinsurance Company, Narcotics Division of the Security Bureau of the Hong Kong Special Administrative Region, the National Health and Medical Research Council Australia; consulting fees from AstraZeneca, Pfizer and Novartis; and honorarium from the Hospital Authority Hong Kong, outside the submitted work. Joseph F. Hayes has received consultancy fees from Wellcome Trust and juli Health.Yun Kwok Wing has received honorarium from Eisai Hong Kong and consultation fees from Eisai Co., Ltd, grants from Research Grants Council (RGC, Hong Kong). Wallis C.Y. Lau reports grant from AIR@InnoHK administered by Innovation and Technology Commission, outside the submitted work. Kenneth K.C. Man received the CW Maplethorpe Fellowship, grants from the National Institute for Health Research, United Kingdom; the European Union Horizon 2020 Framework; Hong Kong Research Grant Council and personal fees from IQVIA Holdings, Inc., unrelated to this work. Ian C.K. Wong has received grants from the Research Grants Council (RGC, Hong Kong), the National Institute for Health Research, United Kingdom, National Health and Medical Research Council in Australia, Innovative Medicines Initiative (IMI), Shire, Janssen-Cilag, Eli-Lily, Pfizer, Bayer, Bristol-Myers Squibb, Takeda, Amgen, AstraZeneca and the European Union FP7 program. He is a member of the National Institute for Health and Clinical Excellence (NICE) ADHD Guideline Group, the British Association for Psychopharmacology ADHD guideline group and an advisor to Shire. He also receives personal fee from IQVIA and Jacobson Pharmaceutical and speaker fees from Janssen and Medice in the previous 3 years. Vanessa W.S. Ng, Miriam T.Y. Leung, Edwin H.M. Lee, and David P.J. Osborn, declare no conflict of interest., (Copyright © 2023. Published by Elsevier B.V.)

Background: Sedentary behaviour is potentially a modifiable risk factor for anxiety disorders, a major source of global disability that typically starts during adolescence. This is the first prospective study of associations between repeated, device-based measures of sedentary behaviour and anxiety symptoms in adolescents., Methods: A UK cohort with 4257 adolescents aged 12 at baseline (56% female). Main exposures were sedentary behaviour and physical activity measured using accelerometers for 7-days at ages 12, 14, and 16. Primary outcome was anxiety symptom scores at age 18 from a Clinical Interview Schedule-Revised. We used adjusted negative binomial regression and iso-temporal substitution methods to analyse the data., Results: We found a positive association between sedentary behaviour at ages 12, 14, and 16, with anxiety symptoms at age 18, independent of total physical activity volume. Theoretically replacing an hour of daily sedentary behaviour for light activity at ages 12, 14, and 16, was associated with lower anxiety symptoms by age 18 by 15.9% (95% CI 8.7-22.4), 12.1% (95% CI 3.4-20.1), and 14.7% (95% CI 4-24.2), respectively. Whereas, theoretically replacing an hour of sedentary behaviour with moderate-to-vigorous physical activity was not associated with differences in anxiety symptoms. These results were robust to a series of sensitivity analyses., Conclusion: Sedentary behaviour is a possible risk factor for increasing anxiety symptoms during adolescence, independent of total physical activity volume. Instead of focusing on moderate-to-vigorous activity, replacing daily sedentary behaviour with light activity during adolescence could be a more suitable method of reducing future anxiety symptoms.

Background: Despite increased rates of physical health problems in people with schizophrenia, bipolar disorder, and other psychotic illnesses, the temporal relationship between physical disease acquisition and diagnosis of a severe mental illness remains unclear. We aimed to determine the cumulative prevalence of 24 chronic physical conditions in people with severe mental illness from 5 years before to 5 years after their diagnosis., Methods: In this cohort study, we used the UK Clinical Practice Research Datalink (CPRD) to identify patients aged 18-100 years who were diagnosed with severe mental illness between Jan 1, 2000, and Dec 31, 2018. Each patient with severe mental illness was matched with up to four individuals in the CPRD without severe mental illness by sex, 5-year age band, primary care practice, and year of primary care practice registration. Individuals in the matched cohort were assigned an index date equal to the date of severe mental illness diagnosis in the patient with severe mental illness to whom they were matched. Our primary outcome was the cumulative prevalence of 24 physical health conditions, based on the Charlson and Elixhauser comorbidity indices, at 5 years, 3 years, and 1 year before and after severe mental illness diagnosis and at the time of diagnosis. We used logistic regression to compare people with severe mental illness with the matched cohort, adjusting for key variables such as age, sex, and ethnicity., Findings: We identified 68 789 patients diagnosed with a severe mental illness between Jan 1, 2000, and Dec 31, 2018, and we matched them to 274 827 patients without a severe mental illness diagnosis. In both cohorts taken together, the median age was 40·90 years (IQR 29·46-56·00), 175 138 (50·97%) people were male, and 168 478 (49·03%) were female. The majority of patients were of White ethnicity (59 867 [87·03%] patients with a severe mental illness and 244 566 [88·99%] people in the matched cohort). The most prevalent conditions at the time of diagnosis in people with severe mental illness were asthma (10 581 [15·38%] of 68 789 patients), hypertension (8696 [12·64%]), diabetes (4897 [7·12%]), neurological disease (3484 [5·06%]), and hypothyroidism (2871 [4·17%]). At diagnosis, people with schizophrenia had increased odds of five of 24 chronic physical conditions compared with matched controls, and nine of 24 conditions were diagnosed less frequently than in matched controls. Individuals with bipolar disorder and other psychoses had increased odds of 15 conditions at diagnosis. At 5 years after severe mental illness diagnosis, these numbers had increased to 13 conditions for schizophrenia, 19 for bipolar disorder, and 16 for other psychoses., Interpretation: Elevated odds of multiple conditions at the point of severe mental illness diagnosis suggest that early intervention on physical health parameters is necessary to reduce morbidity and premature mortality. Some physical conditions might be under-recorded in patients with schizophrenia relative to patients with other severe mental illness subtypes., Funding: UK Office For Health Improvement and Disparities., Competing Interests: Declaration of interests JFH has received consultancy fees from the Wellcome Trust and juli Health. All other authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: People with severe mental illness (SMI) are at higher risk of physical health conditions compared to the general population, however, the impact of specific underlying health conditions on the use of secondary care by people with SMI is unknown. We investigated hospital use in people managed in the community with SMI and five common physical long-term conditions: cardiovascular diseases, COPD, cancers, diabetes and liver disease., Methods: We performed a systematic review and meta-analysis (Prospero: CRD42020176251) using terms for SMI, physical health conditions and hospitalisation. We included observational studies in adults under the age of 75 with a diagnosis of SMI who were managed in the community and had one of the physical conditions of interest. The primary outcomes were hospital use for all causes, physical health causes and related to the physical condition under study. We performed random-effects meta-analyses, stratified by physical condition., Results: We identified 5,129 studies, of which 50 were included: focusing on diabetes (n = 21), cardiovascular disease (n = 19), COPD (n = 4), cancer (n = 3), liver disease (n = 1), and multiple physical health conditions (n = 2). The pooled odds ratio (pOR) of any hospital use in patients with diabetes and SMI was 1.28 (95%CI:1.15-1.44) compared to patients with diabetes alone and pooled hazard ratio was 1.19 (95%CI:1.08-1.31). The risk of 30-day readmissions was raised in patients with SMI and diabetes (pOR: 1.18, 95%CI:1.08-1.29), SMI and cardiovascular disease (pOR: 1.27, 95%CI:1.06-1.53) and SMI and COPD (pOR:1.18, 95%CI: 1.14-1.22) compared to patients with those conditions but no SMI., Conclusion: People with SMI and five physical conditions are at higher risk of hospitalisation compared to people with that physical condition alone. Further research is warranted into the combined effects of SMI and physical conditions on longer-term hospital use to better target interventions aimed at reducing inappropriate hospital use and improving disease management and outcomes., Competing Interests: The authors have declared that no competing interests exist.

Background: Severe mental illness (SMI) is associated with poorer physical health, however the relationship between SMI and cancer is complex and previous study findings are inconsistent. Low incidence of cancer in those with SMI has been attributed to premature mortality, though evidence for this is lacking. We aimed to investigate the relationship between SMI and cancer incidence and mortality, and to assess the effect of premature mortality on cancer incidence rates., Methods: In this UK-wide matched cohort study using primary care records we calculated incidence and mortality rates of all-cancer, and bowel, lung, breast or prostate cancer, in patients with SMI, compared to matched patients without SMI. We used competing risks regression to account for mortality from other causes., Findings: 69,632 patients had an SMI diagnosis. The rate of all-cancer diagnoses was reduced in those with SMI (Hazard ratio (HR):0·95; 95%CI 0·93-0·98) compared to those without SMI, and particularly in those with schizophrenia (HR:0·82; 95%CI 0·77-0·88) compared to those without SMI. When accounting for the competing risk of premature mortality, incidence remained lower only in patients with schizophrenia. All-cause mortality after cancer was increased in the SMI group, and cancer-specific mortality was increased in those with schizophrenia (hazard ratio: 1.96; 95%CI 1.57-2.44)., Interpretation: Patients with schizophrenia have lower rates of cancer diagnosis but higher all-cause and cancer-specific mortality rates following diagnosis compared to those without SMI. Premature mortality does not explain these differences, suggesting the findings reflect barriers to cancer diagnosis and treatment, which need to be identified and addressed., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Mental health concerns in older adults are common, with increasing age-related risks to physical health, mobility and social isolation. Community-based approaches are a key focus of public health strategy in the UK, and may reduce the impact of these risks, protecting mental health and promoting wellbeing. We conducted a review of UK community-based interventions to understand the types of intervention studied and mental health/wellbeing impacts reported., Method: We conducted a scoping review of the literature, systematically searching six electronic databases (2000-2020) to identify academic studies of any non-clinical community intervention to improve mental health or wellbeing outcomes for older adults. Data were extracted, grouped by population targeted, intervention type, and outcomes reported, and synthesised according to a framework categorising community actions targeting older adults., Results: In total, 1,131 full-text articles were assessed for eligibility and 54 included in the final synthesis. Example interventions included: link workers; telephone helplines; befriending; digital support services; group social activities. These were grouped into: connector services, gateway services/approaches, direct interventions and systems approaches. These interventions aimed to address key risk factors: loneliness, social isolation, being a caregiver and living with long-term health conditions. Outcome measurement varied greatly, confounding strong evidence in favour of particular intervention types., Conclusion: The literature is wide-ranging in focus and methodology. Greater specificity and consistency in outcome measurement are required to evidence effectiveness - no single category of intervention yet stands out as 'promising'. More robust evidence on the active components of interventions to promote older adult's mental health is required., (© 2021 The Authors. Health and Social Care in the Community published by John Wiley & Sons Ltd.)

Background: In the UK, acute mental healthcare is provided by in-patient wards and crisis resolution teams. Readmission to acute care following discharge is common. Acute day units (ADUs) are also provided in some areas., Aims: To assess predictors of readmission to acute mental healthcare following discharge in England, including availability of ADUs., Method: We enrolled a national cohort of adults discharged from acute mental healthcare in the English National Health Service (NHS) between 2013 and 2015, determined the risk of readmission to either in-patient or crisis teams, and used multivariable, multilevel logistic models to evaluate predictors of readmission., Results: Of a total of 231 998 eligible individuals discharged from acute mental healthcare, 49 547 (21.4%) were readmitted within 6 months, with a median time to readmission of 34 days (interquartile range 10-88 days). Most variation in readmission (98%) was attributable to individual patient-level rather than provider (trust)-level effects (2.0%). Risk of readmission was not associated with local availability of ADUs (adjusted odds ratio 0.96, 95% CI 0.80-1.15). Statistically significant elevated risks were identified for participants who were female, older, single, from Black or mixed ethnic groups, or from more deprived areas. Clinical predictors included shorter index admission, psychosis and being an in-patient at baseline., Conclusions: Relapse and readmission to acute mental healthcare are common following discharge and occur early. Readmission was not influenced significantly by trust-level variables including availability of ADUs. More support for relapse prevention and symptom management may be required following discharge from acute mental healthcare.

Background: Mental health policy makers require evidence-based information to optimise effective care provision based on local need, but tools are unavailable., Aims: To develop and validate a population-level prediction model for need for early intervention in psychosis (EIP) care for first-episode psychosis (FEP) in England up to 2025, based on epidemiological evidence and demographic projections., Method: We used Bayesian Poisson regression to model small-area-level variation in FEP incidence for people aged 16-64 years. We compared six candidate models, validated against observed National Health Service FEP data in 2017. Our best-fitting model predicted annual incidence case-loads for EIP services in England up to 2025, for probable FEP, treatment in EIP services, initial assessment by EIP services and referral to EIP services for 'suspected psychosis'. Forecasts were stratified by gender, age and ethnicity, at national and Clinical Commissioning Group levels., Results: A model with age, gender, ethnicity, small-area-level deprivation, social fragmentation and regional cannabis use provided best fit to observed new FEP cases at national and Clinical Commissioning Group levels in 2017 (predicted 8112, 95% CI 7623-8597; observed 8038, difference of 74 [0.92%]). By 2025, the model forecasted 11 067 new treated cases per annum (95% CI 10383-11740). For every 10 new treated cases, 21 and 23 people would be assessed by and referred to EIP services for suspected psychosis, respectively., Conclusions: Our evidence-based methodology provides an accurate, validated tool to inform clinical provision of EIP services about future population need for care, based on local variation of major social determinants of psychosis., Competing Interests: Declaration of interest P.B.J. has been a member of scientific advisory boards for Janssen and Ricordati. All other authors have no conflicts of interest to declare.

Background: Sedentary behaviour is potentially a modifiable risk factor for depression and anxiety disorders, but findings have been inconsistent. To assess the associations of sedentary behaviour with depression and anxiety symptoms and estimate the impact of replacing daily time spent in sedentary behaviours with sleep, light, or moderate to vigorous physical activity, using compositional data analysis methods., Methods: We conducted a prospective cohort study in 60,235 UK Biobank participants (mean age: 56; 56% female). Exposure was baseline daily movement behaviours (accelerometer-assessed sedentary behaviour and physical activity, and self-reported total sleep). Outcomes were depression and anxiety symptoms (Patient Health Questionnaire-9 and Generalised Anxiety Disorders-7) at follow-up., Results: Replacing 60 min of sedentary behaviour with light activity, moderate-to-vigorous activity, and sleep was associated with lower depression symptom scores by 1.3% (95% CI, 0.4-2.1%), 12.5% (95% CI, 11.4-13.5%), and 7.6% (95% CI, 6.9-8.4%), and lower odds of possible depression by 0.95 (95% CI, 0.94-0.96), 0.75 (95% CI, 0.74-0.76), and 0.90 (95% CI, 0.90-0.91) at follow-up. Replacing 60 min of sedentary behaviour with moderate-to-vigorous activity and sleep was associated with lower anxiety symptom scores by 6.6% (95% CI, 5.5-7.6%) and 4.5% (95% CI, 3.7-5.2%), and lower odds of meeting the threshold for a possible anxiety disorder by 0.90 (95% CI, 0.89-0.90) and 0.97 (95%CI, 0.96-0.97) at follow-up. However, replacing 60 min of sedentary behaviour with light activity was associated with higher anxiety symptom scores by 4.5% (95% CI, 3.7-5.3%) and higher odds of a possible anxiety disorder by 1.07 (95% CI, 1.06-1.08)., Conclusions: Sedentary behaviour is a risk factor for increased depression and anxiety symptoms in adults. Replacing sedentary behaviour with moderate-to-vigorous activity may reduce mental health risks, but more work is necessary to clarify the role of light activity.

Objective: To use data from electronic health records (EHRs) to describe the demographic, clinical and functional correlates of childhood sexual abuse (CSA) in patients with severe mental illness (SMI), and compare their clinical outcomes (admissions and receipt of antipsychotic medications) to those of patients with no recorded history of CSA., Methods: We applied a string-matching technique to clinical text records of 7000 patients with SMI (non-organic psychotic disorders or bipolar disorder), identifying 619 (8.8%) patients with a recorded history of CSA. Data were extracted from both free-text and structured fields of patients' EHRs., Results: Comorbid diagnoses of major depressive disorder, post-traumatic stress disorder and personality disorders were more prevalent in patients with CSA. Positive psychotic symptoms, depressed mood, self-harm, substance use and aggression were also more prevalent in this group, as were problems with relationships and living conditions. The odds of inpatient admissions were higher in patients with CSA than in those without (adjusted OR = 1.95, 95% CI: 1.64-2.33), and they were more likely to have spent more than 10 days per year as inpatients (adjusted OR = 1.32, 95% CI: 1.07-1.62). Patients with CSA were more likely to be prescribed antipsychotic medications (adjusted OR = 2.48, 95% CI: 1.69-3.66) and be given over 75% of the maximum recommended daily dose (adjusted OR = 1.72, 95% CI: 1.44-2.04)., Conclusion: Data-driven approaches are a reliable, promising avenue for research on childhood trauma. Clinicians should be trained and skilled at identifying childhood adversity in patients with SMI, and addressing it as part of the care plan., (© 2021 The Authors. Acta Psychiatrica Scandinavica published by John Wiley & Sons Ltd.)

Background: Lithium is the most effective treatment in bipolar disorder. Its use is limited by concerns about risk of chronic kidney disease (CKD). We aimed to develop a model to predict risk of CKD following lithium treatment initiation, by identifying individuals with a high-risk trajectory of kidney function., Methods: We used United Kingdom Clinical Practice Research Datalink (CPRD) electronic health records (EHRs) from 2000 to 2018. CPRD Aurum for prediction model development and CPRD Gold for external validation. We used elastic net regularised regression to generate a prediction model from potential features. We performed discrimination and calibration assessments in an external validation data set. We included all patients aged ≥ 16 with bipolar disorder prescribed lithium. To be included patients had to have ≥ 1 year of follow-up before lithium initiation, ≥ 3 estimated glomerular filtration rate (eGFR) measures after lithium initiation (to be able to determine a trajectory) and a normal (≥ 60 mL/min/1.73 m 2 ) eGFR at lithium initiation (baseline). In the Aurum development cohort, 1609 fulfilled these criteria. The Gold external validation cohort included 934 patients. We included 44 potential baseline features in the prediction model, including sociodemographic, mental and physical health and drug treatment characteristics. We compared a full model with the 3-variable 5-year kidney failure risk equation (KFRE) and a 3-variable elastic net model. We used group-based trajectory modelling to identify latent trajectory groups for eGFR. We were interested in the group with deteriorating kidney function (the high-risk group)., Results: The high risk of deteriorating eGFR group included 191 (11.87%) of the Aurum cohort and 137 (14.67%) of the Gold cohort. Of these, 168 (87.96%) and 117 (85.40%) respectively developed CKD 3a or more severe during follow-up. The model, developed in Aurum, had a ROC area of 0.879 (95%CI 0.853-0.904) in the Gold external validation data set. At the empirical optimal cut-point defined in the development dataset, the model had a sensitivity of 0.91 (95%CI 0.84-0.97) and a specificity of 0.74 (95% CI 0.67-0.82). However, a 3-variable elastic net model (including only age, sex and baseline eGFR) performed similarly well (ROC area 0.888; 95%CI 0.864-0.912), as did the KFRE (ROC area 0.870; 95%CI 0.841-0.898)., Conclusions: Individuals at high risk of a poor eGFR trajectory can be identified before initiation of lithium treatment by a simple equation including age, sex and baseline eGFR. Risk was increased in individuals who were younger at commencement of lithium, female and had a lower baseline eGFR. We did not identify strong predicters of eGFR decline specific to lithium-treated patients. Notably, lithium duration and toxicity were not associated with high-risk trajectory.

Background: Acute Day Units (ADUs) provide intensive, non-residential, short-term treatment for adults in mental health crisis. They currently exist in approximately 30% of health localities in England, but there is little research into their functioning or effectiveness, and how this form of crisis care is experienced by service users. This qualitative study explores the views and experiences of stakeholders who use and work in ADUs., Methods: We conducted 36 semi-structured interviews with service users, staff and carers at four ADUs in England. Data were analysed using thematic analysis. Peer researchers collected data and contributed to analysis, and a Lived Experience Advisory Panel (LEAP) provided perspectives across the whole project., Results: Both service users and staff provided generally positive accounts of using or working in ADUs. Valued features were structured programmes that provide routine, meaningful group activities, and opportunities for peer contact and emotional, practical and peer support, within an environment that felt safe. Aspects of ADU care were often described as enabling personal and social connections that contribute to shifting from crisis to recovery. ADUs were compared favourably to other forms of home- and hospital-based acute care, particularly in providing more therapeutic input and social contact. Some service users and staff thought ADU lengths of stay should be extended slightly, and staff described some ADUs being under-utilised or poorly-understood by referrers in local acute care systems., Conclusions: Multi-site qualitative data suggests that ADUs provide a distinctive and valued contribution to acute care systems, and can avoid known problems associated with other forms of acute care, such as low user satisfaction, stressful ward environments, and little therapeutic input or positive peer contact. Findings suggest there may be grounds for recommending further development and more widespread implementation of ADUs to increase choice and effective support within local acute care systems.

Background: Depression and anxiety are common mental disorders that increase physical health risks and are leading causes of global disability. Several forms of physical fitness could be modifiable risk factors for common mental disorders in the population. We examined associations between individual and combined markers of cardiorespiratory fitness and grip strength with the incidence of common mental disorders., Methods: A 7-year prospective cohort study in 152,978 UK Biobank participants. An exercise test and dynamometer were used to measure cardiorespiratory and grip strength, respectively. We used Patient Health Questionnaire-9 and Generalised Anxiety Disorder-7 scales to estimate the incidence of common mental disorders at follow-up., Results: Fully adjusted, longitudinal models indicated a dose-response relationship. Low and medium cardiorespiratory fitness was associated with 1.485 (95% CIs, 1.301 to 1.694, p <  0.001) and 1.141 (95% CIs, 1.005 to 1.297, p = 0.041) higher odds of depression or anxiety, compared to high cardiorespiratory fitness. Low and medium grip strength was associated with 1.381 (95% CIs, 1.315 to 1.452, p <  0.001) and 1.116 (95% CIs, 1.063 to 1.172, p <  0.001) higher odds of common mental disorder compared to high grip strength. Individuals in the lowest group for both cardiorespiratory fitness and grip strength had 1.981 (95% CIs, 1.553 to 2.527, p <  0.001) higher odds of depression, 1.599 (95% CIs, 1.148 to 2.118, p = 0.004) higher odds of anxiety, and 1.814 (95% CIs, 1.461 to 2.252, p <  0.001) higher odds of either common mental disorder, compared to high for both types of fitness., Conclusions: Objective cardiorespiratory and muscular fitness markers represent modifiable risk factors for common mental disorders. Public health strategies to reduce common mental disorders could include combinations of aerobic and resistance activities.

Background: Characteristics and outcomes of patients presenting to Emergency Departments (EDs) have been under-examined. This paper describes the characteristics and risk of repeat suicidality amongst patients presenting to EDs with (1) suicidal ideation and (2) self-harm, compared to (3) controls in mental health crisis., Methods: The Clinical Record Interactive Search tool identified 2211 patients who presented to three London EDs with suicidal ideation or self-harm, and 1108 control patients. All patients received a full psychosocial assessment. Chi-squared tests examined group characteristics. Cox regression models assessed the risk of re-presentation with suicidal ideation or self-harm within one year., Results: There were a higher proportion of females and individuals under the age of 25 in the self-harm group. Patients presenting with suicidal ideation or self-harm were more likely to be white, live in more deprived areas, and less likely to receive a psychiatric diagnosis within one year compared to controls. Risk of repeat suicidality within one year was 3-4 times higher in those with baseline suicidal ideation (adjusted HR = 3.66, 95% CI 2.44-5.48) or self-harm (HR = 3.53 95% CI 2.47-5.04) compared to controls., Limitations: To be included patients needed to have a full psychosocial assessment. Incomplete records meant 21.4% of the sample was excluded. This will have introduced bias which might confound observed associations., Conclusion: Individuals presenting with either suicidal ideation or self-harm have similar risk for re-presentation within one year. Both groups would benefit from personalised risk management plans and active follow-up to reduce the risk of repeat suicidal behaviour., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Purpose: We aimed to test the hypothesis that among people who experience sudden bereavement, loneliness is associated with post-bereavement suicide attempt and post-bereavement suicidal ideation, even when adjusting for network size., Methods: We analysed cross-sectional data collected in the 2010 UCL Bereavement Study, to identify 3193 respondents who had experienced sudden bereavement. We used multivariable logistic regression to test for an association between loneliness (using a newly-developed eight-item loneliness measure) and post-bereavement suicide attempt and suicidal ideation, adjusting for socio-demographic factors, pre-bereavement depression and self-harm, and network size., Results: Among bereaved adults, loneliness was significantly associated with probability of post-bereavement suicide attempt (AOR 1.19; 95% CI 1.14-1.25) and of post-bereavement suicidal ideation (AOR 1.24; 95% CI 1.20-1.28), with estimates unchanged by adding perceived stigma of the bereavement to adjusted models. There was no association between suicide bereavement and loneliness (adjusted coefficient 0.22; 95% CI - 0.12 to 0.45; p = 0.063). The association of loneliness and suicide attempt risk was similar whether participants were bereaved by suicide or not., Conclusions: People who report feeling lonely after sudden bereavement are more likely to make a suicide attempt after their loss, even when taking into account their network size and the perceived stigma of the sudden bereavement. There is no evidence that the effects of loneliness on suicidality are specific to suicide bereavement. This work identifies loneliness as a potential target for suicide prevention interventions among bereaved people. It also fuels interest in longitudinal research investigating loneliness as a putative mediator of suicide risk.

Aim: Personality Disorders (PD) often share clinical and phenomenological overlap with psychotic disorders, especially at onset. However, there is little research on comorbid PD among people experiencing first episode psychosis. We examined the prevalence of PD recording and its sociodemographic and clinical correlates in people accepted to Early Intervention in Psychosis (EIP) services., Methods: Participants were aged 16-35, accepted into 6 EIP services for suspected psychosis, as part of the Social Epidemiology of Psychoses in East Anglia (SEPEA) study. PD was recorded by clinicians according to ICD-10. Multilevel logistic regression was performed., Results: Of 798 participants, 76 people (9.5%) received a clinical diagnosis of PD, with emotionally unstable PD (75.0%, N = 57) the most common subtype. In multivariable analysis, risk factors for PD included female sex (odds ratio [OR]: 3.4; 95% CI: 2.0-5.7), absence of psychotic disorder after acceptance to EIP (OR: 3.0; 95% CI: 1.6-5.5), more severe hallucinations (OR: 1.6; 95% CI: 1.2-2.1), and lower parental SES (OR: 1.4; 95% CI: 1.1-1.8). Compared with the white British, black and minority ethnic groups were less likely to receive a PD diagnosis (OR: 0.3; 95% CI: 0.1-0.7). There was no association between PD and neighbourhood-level deprivation or population-density., Conclusions: Recording of a PD diagnosis was three times more common amongst participants later found not to meet threshold criteria for psychotic disorder, implying phenomenological overlap at referral which highlights difficulties encountered in accurate diagnostic assessment, treatment and onward referral. People with PD experienced more individual-level, but not neighbourhood-level social disadvantage in an already disadvantaged sample., Competing Interests: No authors have competing interests.

Research that provides an evidence base for the pharmacotherapy of people with mental disorders is needed. The abundance of digital data has facilitated pharmacoepidemiology and, in particular, observational research on the effectiveness of real-world medication. Advantages of pharmacoepidemiological research are the availability of large patient samples, and coverage of under-researched subpopulations in their naturalistic conditions. Such research is also cheaper and quicker to do than randomised controlled trials, meaning that issues regarding generic medication, stopping medication (deprescribing), and long-term outcomes are more likely to be addressed. Pharmacoepidemiological methods can also be extended to pharmacovigilance and to aid the development of new purposes for existing drugs. Drawbacks of observational pharmacoepidemiological studies come from the non-randomised nature of treatment selection, leading to confounding by indication. Potential methods for managing this drawback include active comparison groups, within-individual designs, and propensity scoring. Many of the more rigorous pharmacoepidemiology studies have been strengthened through multiple analytical approaches triangulated to improve confidence in inferred causal relationships. With developments in data resources and analytical techniques, it is encouraging that guidelines are beginning to include evidence from robust observational pharmacoepidemiological studies alongside randomised controlled trials. Collaboration between guideline writers and researchers involved in pharmacoepidemiology could help researchers to answer the questions that are important to policy makers and ensure that results are integrated into the evidence base. Further development of statistical and data science techniques, alongside public engagement and capacity building (data resources and researcher base), will be necessary to take full advantage of future opportunities., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: To estimate the potential gain in life expectancy from addressing modifiable risk factors for all-cause mortality (excluding suicide and deaths from accidents or violence) across specific serious mental illness (SMI) subgroups, namely schizophrenia, schizoaffective disorders, and bipolar disorders in a Western population., Methods: We have used relative risks from recent meta-analyses to estimate the population attribution fraction (PAF) due to specific modifiable risk factors known to be associated with all-cause mortality within SMI. The potential gain in life expectancy at birth, age 50 and age 65 years were assessed by estimating the combined effect of modifiable risk factors from different contextual levels (behavioural, healthcare, social) and accounting for the effectiveness of existing interventions tackling these factors. Projections for annual gain in life expectancy at birth during a two-decade was estimated using the Annual Percentage Change (APC) formula. The predicted estimates were based on mortality rates for year 2014-2015., Results: Based on the effectiveness of existing interventions targeting these modifiable risk factors, we estimated potential gain in life expectancy at birth of four (bipolar disorders), six (schizoaffective disorders), or seven years (schizophrenia). The gain in life expectancy at age 50 years was three (bipolar disorders) or five (schizophrenia and schizoaffective disorders) years. The projected gain in life expectancy at age 65 years was three (bipolar disorders) or four (schizophrenia and schizoaffective disorders) years., Conclusions: The implementation of existing interventions targeting modifiable risk factors could narrow the current mortality gap between the general and the SMI populations by 24% (men) to 28% (women). These projections represent ideal circumstances and without the limitation of overestimation which often comes with PAFs., Competing Interests: Matthew Hotopf is principal investigator of the RADAR-CNS programme, a precompetitive public private partnership funded by the Innovative Medicines Initiative and European Federation of Pharmaceutical Industries and Associations (EFPIA). The programme receives support from Janssen, Biogen, MSD, UCB and Lundbeck. In the last 3 years, Fiona Gaughran has received support or honoraria from Lundbeck, Hikma, Otsuka and Sunovion, and has a family member who has professional links to Lilly and GSK, including shares.

Background: Identifying modifiable risk factors is essential to reduce the prevalence adolescent depression. Self-report data suggest that physical activity and sedentary behaviour might be associated with depressive symptoms in adolescents. We examined associations between depressive symptoms and objectively measured physical activity and sedentary behaviour in adolescents., Methods: From a population-based cohort of adolescents whose mothers were invited to participate in the Avon Longitudinal Study of Parents and Children (ALSPAC) study, we included participants with at least one accelerometer recording and a Clinical Interview Schedule-Revised (CIS-R) depression score at age 17·8 years (reported as age 18 years hereafter). Amounts of time spent in sedentary behaviour and physical activity (light or moderate-to-vigorous) were measured with accelerometers at around 12 years, 14 years, and 16 years of age. Total physical activity was also recorded as count per minute (CPM), with raw accelerometer counts averaged over 60 s epochs. Associations between the physical activity and sedentary behaviour variables and depression (CIS-R) scores at age 18 years were analysed with regression and group-based trajectory modelling., Findings: 4257 adolescents from the 14 901 enrolled in the ALSPAC study had a CIS-R depression score at age 18 years. Longitudinal analyses included 2486 participants at age 12 years, 1938 at age 14 years, and 1220 at age 16 years. Total follow-up time was 6 years. Total physical activity decreased between 12 years and 16 years of age, driven by decreasing durations of light activity (mean 325·66 min/day [SD 58·09] at 12 years; 244·94 min/day [55·08] at 16 years) and increasing sedentary behaviour (430·99 min/day [65·80]; 523·02 min/day [65·25]). Higher depression scores at 18 years were associated with a 60 min/day increase in sedentary behaviour at 12 years (incidence rate ratio [IRR] 1·111 [95% CI 1·051-1·176]), 14 years (1·080 [1·012-1·152]), and 16 years of age (1·107 [1·015-1·208]). Depression scores at 18 years were lower for every additional 60 min/day of light activity at 12 years (0·904 [0·850-0·961]), 14 years (0·922 [0·857-0·992]), and 16 years of age (0·889 [0·809-0·974]). Group-based trajectory modelling across 12-16 years of age identified three latent subgroups of sedentary behaviour and activity levels. Depression scores were higher in those with persistently high (IRR 1·282 [95% CI 1·061-1·548]) and persistently average (1·249 [1·078-1·446]) sedentary behaviour compared with those with persistently low sedentary behaviour, and were lower in those with persistently high levels of light activity (0·804 [0·652-0·990]) compared with those with persistently low levels of light activity. Moderate-to-vigorous physical activity (per 15 min/day increase) at age 12 years (0·910 [0·857-0·966]) and total physical activity (per 100 CPM increase) at ages 12 years (0·941 [0·910-0·972]) and 14 years (0·965 [0·932-0·999]), were negatively associated with depressive symptoms., Interpretation: Sedentary behaviour displaces light activity throughout adolescence, and is associated with a greater risk of depressive symptoms at 18 years of age. Increasing light activity and decreasing sedentary behaviour during adolescence could be an important target for public health interventions aimed at reducing the prevalence of depression., Funding: Details of funding are provided in the Acknowledgments., (Copyright © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Policies addressing the physical health of people with mental disorders have historically focused on those with severe mental illness (SMI), giving less prominence to the more prevalent common mental disorders (CMDs). Little is known about the comparative physical health outcomes of these patient groups. We aimed to first compare the: (a) number of past-year chronic physical conditions and (b) recent physical health service utilization between CMDs vs. SMI, and secondly compare these outcomes between people with CMDs vs. people without mental disorders., Methods: We analyzed cross-sectional data from the third Adult Psychiatric Morbidity Survey, a representative sample of the English population. We determined the presence of physical conditions and health service utilization by self-report and performed logistic regression models to examine associations of these outcomes between participant groups., Results: Past-year physical conditions were reported by the majority of participants (CMDs, n = 815, 62.1%; SMI = 27, 63.1%) with no variation in the adjusted odds of at least one physical condition between diagnoses (odds ratio [OR] = 0.96, 95% confidence intervals [CI] 0.42-1.98, p = 0.784). People with CMDs were significantly more likely to be recently hospitalized relative to with those with SMI (OR = 6.33, 95% CI 5.50-9.01, p < 0.05). Having a CMD was associated with significantly higher odds of past-year physical conditions and recent health service utilization (all p < 0.001) compared with the general population., Conclusions: People with CMDs experience excess physical health morbidities in a similar pattern to those found among people with SMI, while their somatic hospitalization rates are even more elevated. Findings highlight the importance of recalibrating existing public health strategies to bring equity to the physical health needs of this patient group.

We aimed to investigate whether daily fluctuations in mental health-relevant Twitter posts are associated with daily fluctuations in mental health crisis episodes. We conducted a primary and replicated time-series analysis of retrospectively collected data from Twitter and two London mental healthcare providers. Daily numbers of 'crisis episodes' were defined as incident inpatient, home treatment team and crisis house referrals between 2010 and 2014. Higher volumes of depression and schizophrenia tweets were associated with higher numbers of same-day crisis episodes for both sites. After adjusting for temporal trends, seven-day lagged analyses showed significant positive associations on day 1, changing to negative associations by day 4 and reverting to positive associations by day 7. There was a 15% increase in crisis episodes on days with above-median schizophrenia-related Twitter posts. A temporal association was thus found between Twitter-wide mental health-related social media content and crisis episodes in mental healthcare replicated across two services. Seven-day associations are consistent with both precipitating and longer-term risk associations. Sizes of effects were large enough to have potential local and national relevance and further research is needed to evaluate how services might better anticipate times of higher risk and identify the most vulnerable groups.

Background: Particulate air pollution's physical health effects are well known, but associations between particulate matter (PM) exposure and mental illness have not yet been established. However, there is increasing interest in emerging evidence supporting a possible etiological link., Objectives: This systematic review aims to provide a comprehensive overview and synthesis of the epidemiological literature to date by investigating quantitative associations between PM and multiple adverse mental health outcomes (depression, anxiety, bipolar disorder, psychosis, or suicide)., Methods: We undertook a systematic review and meta-analysis. We searched Medline, PsycINFO, and EMBASE from January 1974 to September 2017 for English-language human observational studies reporting quantitative associations between exposure to PM < 1.0 μ m in aerodynamic diameter (ultrafine particles) and PM < 2.5 and < 10 μ m in aerodynamic diameter ( PM 2.5 and PM 10 , respectively) and the above psychiatric outcomes. We extracted data, appraised study quality using a published quality assessment tool, summarized methodological approaches, and conducted meta-analyses where appropriate., Results: Of 1,826 citations identified, 22 met our overall inclusion criteria, and we included 9 in our primary meta-analyses. In our meta-analysis of associations between long-term ( > 6   months ) PM 2.5 exposure and depression ( n = 5 studies), the pooled odds ratio was 1.102 per 10 - μ g / m 3 PM 2.5 increase (95% CI: 1.023, 1.189; I 2 = 0.00 % ). Two of the included studies investigating associations between long-term PM 2.5 exposure and anxiety also reported statistically significant positive associations, and we found a statistically significant association between short-term PM 10 exposure and suicide in meta-analysis at a 0-2 d cumulative exposure lag., Discussion: Our findings support the hypothesis of an association between long-term PM 2.5 exposure and depression, as well as supporting hypotheses of possible associations between long-term PM 2.5 exposure and anxiety and between short-term PM 10 exposure and suicide. The limited literature and methodological challenges in this field, including heterogeneous outcome definitions, exposure assessment, and residual confounding, suggest further high-quality studies are warranted to investigate potentially causal associations between air pollution and poor mental health. https://doi.org/10.1289/EHP4595.

Background: Physical activity is associated with a lower incidence of common mental health disorder, but less is known about the impact of cardiorespiratory fitness (CRF)., Methods: In this review, we systematically evaluated the relationship between CRF and the incidence of common mental health disorders in prospective cohort studies. We systematically searched six major electronic databases from inception to 23rd of May 2019. We assessed study quality using the Newcastle-Ottawa scale., Results: We were able to pool the hazard ratios (HRs) and 95% confidence intervals (CIs) of four studies including at least 27,733,154 person-years of data. We found that low CRF (HR = 1.47, [95% CI 1.23 - 1.76] p < 0.001 I 2  = 85.1) and medium CRF (HR = 1.23, [95% CI 1.09 - 1.38] p < 0.001 I 2  = 87.20) CRF are associated with a 47% and 23% greater risk of a common mental health disorders respectively, compared with high CRF. We found evidence to suggest a dose-response relationship between CRF and the risk of common mental health disorders., Limitations: We were only able to identify a small number of eligible studies from our search and heterogeneity was substantial in the subsequent meta-analysis., Conclusions: Our findings indicate that there is a longitudinal association between CRF levels and the risk of a common mental health disorder. CRF levels could be useful for identifying and preventing common mental health disorders at a population-level., (Crown Copyright © 2019. Published by Elsevier B.V. All rights reserved.)

Objective: To determine clinical predictors of lithium response in bipolar disorder., Methods: Systematic review of studies examining clinical predictors of lithium response was conducted. Meta-analyses were performed when ≥2 studies examined the same potential predictor., Results: A total of 71 studies, including over 12 000 patients, identified six predictors of good response: mania-depression-interval sequence [odds ratio (OR): 4.27; 95% CI: 2.61, 6.97; P < 0.001], absence of rapid cycling (OR for rapid cycling: 0.30; 95% CI: 0.17, 0.53; P < 0.001), absence of psychotic symptoms (OR for psychotic symptoms: 0.52; 95% CI: 0.34, 0.79; P = 0.002), family history of bipolar disorder (OR: 1.61; 95% CI: 1.03, 2.52; P = 0.036), shorter prelithium illness duration [standardised mean difference (SMD): -0.26; 95% CI: -0.41, -0.12; P < 0.001] and later age of onset (SMD: 0.17; 95% CI: 0.02, 0.36; P = 0.029). Additionally, higher body mass index was associated with poor response in two studies (SMD: -0.61; 95% CI: -0.90, -0.32; P < 0.001). There was weak evidence for number of episodes prior to lithium treatment (SMD: -0.42; 95% CI: -0.84, -0.01; P = 0.046), number of hospitalisations before lithium (SMD: -0.40; 95% CI: -0.81, 0.01; P = 0.055) and family history of lithium response (OR: 10.28; 95% CI: 0.66, 161.26; P = 0.097)., Conclusions: The relative importance of these clinical characteristics should be interpreted with caution because of potential biases and confounding., (© 2019 The Authors Acta Psychiatrica Scandinavica Published by John Wiley & Sons Ltd.)

Background: We aimed to determine whether late adolescent visual impairment is associated with later psychosis., Methods: We conducted a longitudinal cohort study of Swedish male military conscripts aged 18 or 19 years from January 1, 1974, through December 31, 1997 (N = 1140710). At conscription, uncorrected and optometry-lens-corrected distance visual acuity was measured. Participants were then followed up to see if they received an inpatient diagnosis of non-affective psychotic disorder, including schizophrenia (N = 10769). Multivariable Cox modeling was used to estimate differences between groups., Results: After adjustment for confounders, those with severe impairment before optical correction in their best eye (decimal fraction <0.3) had an increased psychosis rate compared to those with normal uncorrected vision (decimal fraction 1.0) (hazard ratio [HR] 1.26, 95% CI 1.16-1.37). Larger interocular visual acuity difference was associated with an increased psychosis rate (adjusted HR 1.49, 95% CI 1.37-1.63 in those with differences >0.5 compared to those with no between eye acuity difference). Individuals with impaired vision that could not be corrected to normal with lenses had highest rates of psychosis (best eye adjusted HR 1.56; 95% CI 1.33-1.82), those with imperfect, but correctable vision also had elevated rates (best eye adjusted HR 1.21; 95% CI 1.15-1.28). Individuals with visual impairment had higher rates of psychosis than their full siblings with normal vision (adjusted HR 1.20, 95% CI 1.07-1.35)., Conclusions: Impaired visual acuity is associated with non-affective psychosis. Visual impairment as a phenotype in psychosis requires further consideration., (© The Author(s) 2018. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.)

Importance: Drug repurposing is potentially cost-effective, low risk, and necessary in psychiatric drug development. The availability of large, routine data sets provides the opportunity to evaluate the potential for currently used medication to benefit people with serious mental illness (SMI)., Objective: To determine whether hydroxylmethyl glutaryl coenzyme A reductase inhibitors (HMG-CoA RIs), L-type calcium channel (LTCC) antagonists, and biguanides are associated with reduced psychiatric hospitalization and self-harm in individuals with SMI., Design, Setting, and Participants: These within-individual cohort studies of patients with SMI compared rates of psychiatric hospitalization and self-harm during periods of exposure and nonexposure to the study drugs, with adjusting for a number of time-varying covariates. Participants included 142 691 individuals from the entire population of Sweden with a diagnosis of bipolar disorder (BPD), schizophrenia, or nonaffective psychosis (NAP) who were 15 years or older and who were treated with psychiatric medication from October 1, 2005, through December 31, 2016. Data were analyzed from April 1 through August 31, 2018., Interventions: Treatment with HMG-CoA RIs, LTCC antagonists, or biguanides., Main Outcomes and Measures: Psychiatric hospitalizations and self-harm admissions., Results: Among the 142 691 eligible participants, the HMG-CoA RI exposure periods were associated with reduced rates of psychiatric hospitalization in BPD (adjusted hazard ratio [aHR], 0.86; 95% CI, 0.83-0.89; P < .001), schizophrenia (aHR, 0.75; 95% CI, 0.71-0.79; P < .001), and NAP (aHR, 0.80; 95% CI, 0.75-0.85; P < .001) and reduced self-harm rates in BPD (aHR, 0.76; 95% CI, 0.66-0.86; P < .001) and schizophrenia (aHR, 0.58; 95% CI, 0.45-0.74; P < .001). Exposure to LTCC antagonists was associated with reduced rates of psychiatric hospitalization and self-harm in subgroups with BPD (aHRs, 0.92 [95% CI, 0.88-0.96; P < .001] and 0.81 [95% CI, 0.68-0.95; P = .01], respectively), schizophrenia (aHRs, 0.80 [95% CI, 0.74-0.85; P < .001] and 0.30 [95% CI, 0.18-0.48; P < .001], respectively), and NAP (aHRs, 0.89 [95% CI, 0.83-0.96; P = .002] and 0.56 [95% CI, 0.42-0.74; P < .001], respectively). During biguanide exposure, psychiatric hospitalization rates were reduced in subgroups with BPD (aHR, 0.80; 95% CI, 0.77-0.84; P < .001), schizophrenia (aHR, 0.73; 95% CI, 0.69-0.77; P < .001), and NAP (aHR, 0.85; 95% CI, 0.79-0.92; P < .001), and self-harm was reduced in BPD (aHR, 0.73; 95% CI, 0.62-0.84; P < .001) and schizophrenia (aHR, 0.64; 95% CI, 0.48-0.85; P < .001)., Conclusions and Relevance: This study provides additional evidence that exposure to HMG-CoA RIs, LTCC antagonists, and biguanides might lead to improved outcomes for individuals with SMI. Given the well-known adverse event profiles of these agents, they should be further investigated as repurposed agents for psychiatric symptoms.

Background: Mounting evidence implicates early life and prenatal immune disturbances in the etiology of severe mental illnesses. Asthma is a common illness associated with chronic aberrant immune responses. We aimed to determine if asthma in childhood and parents is associated with bipolar and schizophrenia spectrum disorders., Methods: A cohort study including all children born in Sweden 1973-1995 (N > 2 million) assessing associations between childhood hospitalization for asthma, parental asthma during and pre-pregnancy, and subsequent bipolar and schizophrenia spectrum disorders., Results: Children with hospitalizations for asthma between 11 and 15 years had increased rates of bipolar (adjusted hazard ratio [aHR] = 1.73, 95% confidence interval [CI] = 1.21-2.47) and schizophrenia spectrum disorders (aHR = 1.62, 95% CI = 1.08-2.42). However, there was no association with asthma before aged 11. These results were supported by an analysis of siblings discordant for asthma. We found an association between both maternal and paternal asthma and bipolar disorder (aHR = 1.60, 95% CI = 1.27-2.02, and aHR = 1.44, 95% CI = 1.08-1.93, respectively), but not between parental asthma and schizophrenia spectrum disorders., Conclusions: As far as we are aware, this is the first study to find increased risk of bipolar disorder in children of individuals with asthma. Asthma admissions before aged 11 do not appear to be linked to bipolar or schizophrenia spectrum disorders. Taken together, our results do not suggest a straightforward link between asthma and severe mental illness via neurodevelopmental effects of inflammation, but potentially there is shared genetic vulnerability. This finding has implications for understanding the differential pathogenic mechanisms of bipolar and schizophrenia spectrum disorders., (© The Author(s) 2018. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.)

Background: In vitro and animal studies have suggested that trazodone, a licensed antidepressant, may protect against dementia. However, no studies have been conducted to assess the effect of trazodone on dementia in humans. This electronic health records study assessed the association between trazodone use and the risk of developing dementia in clinical practice., Methods and Findings: The Health Improvement Network (THIN), an archive of anonymised medical and prescribing records from primary care practices in the United Kingdom, contains records of over 15 million patients. We assessed patients from THIN aged ≥50 years who received at least two consecutive prescriptions for an antidepressant between January 2000 and January 2017. We compared the risk of dementia among patients who were prescribed trazodone to that of patients with similar baseline characteristics prescribed other antidepressants, using a Cox regression model with 1:5 propensity score matching. Patients prescribed trazodone who met the inclusion criteria (n = 4,716; 59.2% female) were older (mean age 70.9 ± 13.1 versus 65.6 ± 11.4 years) and were more likely than those prescribed other antidepressants (n = 420,280; 59.7% female) to have cerebrovascular disease and use anxiolytic or antipsychotic drugs. After propensity score matching, 4,596 users of trazadone and 22,980 users of other antidepressants were analysed. The median time to dementia diagnosis for people prescribed trazodone was 1.8 years (interquartile range [IQR] = 0.5-5.0 years). Incidence of dementia among patients taking trazodone was higher than in matched users of other antidepressants (1.8 versus 1.1 per 100 person-years), with a hazard ratio (HR) of 1.80 (95% confidence interval [CI] 1.56-2.09; p < 0.001). However, our results do not suggest a causal association. When we restricted the control group to users of mirtazapine only in a sensitivity analysis, the findings were very similar to the results of the main analysis. The main limitation of our study is the possibility of indication bias, because people in the prodromal stage of dementia might be preferentially prescribed trazodone. Due to the observational nature of this study, we cannot rule out residual confounding., Conclusions: In this study of UK population-based electronic health records, we found no association between trazodone use and a reduced risk of dementia compared with other antidepressants. These results suggest that the clinical use of trazodone is not associated with a reduced risk of dementia., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: ICKW has received research funding from Bristol-Myers Squibb, Pfizer, Janssen, the Hong Kong Research Grants Council, and the Hong Kong Health and Medical Research Fund outside the submitted work. KKCM has received personal fees from IQVIA outside the submitted work. JK is an employee of IQVIA. There are no other relationships or activities that could appear to have influenced the submitted work.

Background: Potentially modifiable risk factors for developing dementia have been identified. However, risk factors for increased mortality in patients with diagnosed dementia are not well understood. Identifying factors that influence prognosis would help clinicians plan care and address unmet needs.AimsTo investigate diagnosed depression and sociodemographic factors as predictors of mortality in patients with dementia in UK secondary clinical care services., Method: We conducted a cohort study of patients with a dementia diagnosis in an electronic health records database in a UK National Health Service mental health trust., Results: In 3374 patients with 10 856 person-years of follow-up, comorbid depression was not associated with mortality (adjusted hazard ratio 0.94; 95% CI 0.71-1.24). Single patients had higher mortality than those who were married (adjusted hazard ratio 1.25; 95% CI 1.03-1.50). Patients of Asian ethnicity had lower mortality rates than White British patients (adjusted hazard ratio 0.50; 95% CI 0.34-0.73)., Conclusions: Clinically diagnosed depression does not increase mortality in patients with dementia. Patients who are single are a potential high-mortality risk group. Lower mortality rates in Asian patients with dementia that have been reported in the USA also apply in the UK.Declaration of interestNone.

Quantitative studies have found that suicide bereavement is associated with suicide attempt, and is perceived as the most stigmatising of sudden losses. Their findings also suggest that perceived stigma may explain the excess suicidality. There is a need to understand the nature of this stigma and address suicide risk in this group. We aimed to describe and compare the nature of the experiences of stigma reported by people bereaved by suicide, sudden unnatural death, and sudden natural death, and identify any commonalities and unique experiences. We conducted a population-based cross-sectional survey of 659,572 staff and students at 37 British higher educational institutions in 2010, inviting those aged 18-40 who had experienced sudden bereavement of a close contact since the age of 10 to take part in an on-line survey and to volunteer for an interview to discuss their experiences. We used maximum variation sampling from 1398 volunteer interviewees to capture a range of experiences, and conducted individual face-to-face semi-structured interviews to explore perceptions of stigma and support. We continued sampling until no new themes were forthcoming, reaching saturation at n = 27 interviews (11 participants bereaved by suicide). We employed thematic analysis to identify any distinct dimensions of reported stigma, and any commonalities across the three groups. We identified two key themes: specific negative attitudes of others, and social awkwardness. Both themes were common to interviewees bereaved by suicide, sudden unnatural death, and sudden natural death. All interviewees reported the experience of stigmatising social awkwardness, but this may have been experienced more acutely by those bereaved by suicide due to self-stigma. This study provides evidence of a persistent death taboo in relation to sudden deaths. There is potential for anti-stigma interventions to reduce the isolation and social awkwardness perceived by people bereaved suddenly, particularly after suicide loss., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Electronic health records (EHRs) are widely used in mental health services. Case registers using EHRs from secondary mental healthcare have the potential to deliver large-scale projects evaluating mental health outcomes in real-world clinical populations., Methods: We describe the Camden and Islington NHS Foundation Trust (C&I) Research Database which uses the Clinical Record Interactive Search (CRIS) tool to extract and de-identify routinely collected clinical information from a large UK provider of secondary mental healthcare, and demonstrate its capabilities to answer a clinical research question regarding time to diagnosis and treatment of bipolar disorder., Results: The C&I Research Database contains records from 108,168 mental health patients, of which 23,538 were receiving active care. The characteristics of the patient population are compared to those of the catchment area, of London, and of England as a whole. The median time to diagnosis of bipolar disorder was 76 days (interquartile range: 17-391) and median time to treatment was 37 days (interquartile range: 5-194). Compulsory admission under the UK Mental Health Act was associated with shorter intervals to diagnosis and treatment. Prior diagnoses of other psychiatric disorders were associated with longer intervals to diagnosis, though prior diagnoses of schizophrenia and related disorders were associated with decreased time to treatment., Conclusions: The CRIS tool, developed by the South London and Maudsley NHS Foundation Trust (SLaM) Biomedical Research Centre (BRC), functioned very well at C&I. It is reassuring that data from different organizations deliver similar results, and that applications developed in one Trust can then be successfully deployed in another. The information can be retrieved in a quicker and more efficient fashion than more traditional methods of health research. The findings support the secondary use of EHRs for large-scale mental health research in naturalistic samples and settings investigated across large, diverse geographical areas.

Background Bipolar disorder and schizophrenia are associated with increased mortality relative to the general population. There is an international emphasis on decreasing this excess mortality. Aims To determine whether the mortality gap between individuals with bipolar disorder and schizophrenia and the general population has decreased. Method A nationally representative cohort study using primary care electronic health records from 2000 to 2014, comparing all patients diagnosed with bipolar disorder or schizophrenia and the general population. The primary outcome was all-cause mortality. Results Individuals with bipolar disorder and schizophrenia had elevated mortality (adjusted hazard ratio (HR) = 1.79, 95% CI 1.67-1.88 and 2.08, 95% CI 1.98-2.19 respectively). Adjusted HRs for bipolar disorder increased by 0.14/year (95% CI 0.10-0.19) from 2006 to 2014. The adjusted HRs for schizophrenia increased gradually from 2004 to 2010 (0.11/year, 95% CI 0.04-0.17) and rapidly after 2010 (0.34/year, 95% CI 0.18-0.49). Conclusions The mortality gap between individuals with bipolar disorder and schizophrenia, and the general population is widening., Competing Interests: Declaration of interestNone., (© The Royal College of Psychiatrists 2017.)

Background: Severe mental illness is associated with increased morbidity and mortality. The elevated risk of blood-borne viruses (BBVs) in people with severe mental illness is of concern, but the full extent of this problem is unclear. We aimed to determine the prevalence of and risk factors for BBVs in people with severe mental illness., Methods: In this nationwide, population-based, cross-sectional study, we estimated the point prevalence of HIV, hepatitis B (HBV), and hepatitis C (HCV) in people with severe mental illness, including the total adult (≥18 years) Swedish population. We defined severe mental illness as a clinical diagnosis of schizophrenia, schizoaffective disorder, bipolar disorder, or other psychotic illness according to the Swedish version of the International Statistical Classification of Diseases version 8, 9, or 10. We used multivariable logistic regression to determine the odds of BBVs in individuals with severe mental illness, relative to the general population, and to identify independent risk factors (age, sex, immigration status, socioeconomic status, education, and substance misuse) for BBV infection. We also did a sensitivity analysis excluding BBV diagnoses made before the introduction of the Register for Infection Disease Control (1997)., Findings: Of 6 815 931 adults in Sweden, 97 797 (1·43%) individuals had a diagnosis of severe mental illness. Prevalence of BBVs was elevated in people with severe mental illness, of which 230 (0·24%) had HIV, 518 (0·53%) had HBV, and 4476 (4·58%) had HCV. After accounting for sociodemographic characteristics, the odds of HIV were 2·57 (95% CI 2·25-2·94, p<0·0001) times higher in people with severe mental illness than in the general population, whereas the odds of HBV were 2·29 (2·09-2·51, p<0·0001) times higher and the odds of HCV were 6·18 (5·98-6·39, p<0·0001) times higher. Substance misuse contributed most to the increased risk of BBV: after adjustment, odds ratios were 1·61 (1·40-1·85, p<0·0001) for HIV, 1·28 (1·16-1·41, p<0·0001) for HBV, and 1·72 (1·67-1·78, p<0·0001) for HCV., Interpretation: Our results highlight the need to address the issue of higher prevalence of BBVs in people with severe mental illness and identify interventions preventing infection. Targeting of comorbid substance misuse would have particular effect on reduction of BBV prevalence in this population., Funding: Medical Research Council and Swedish Research Council., (Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)