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Background.Generalized anxiety disorder (GAD) and panic disorder (PD) differ in their biology and co-morbidities. We hypothesized that GAD but not PD symptoms at the age of 15 years are associated with depression diagnosis at 18 years.Method.Using longitudinal data from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort we examined relationships of GAD and PD symptoms (measured by the Development and Well-Being Assessment) at 15 years with depression at 18 years (by the Clinical Interview Schedule – Revised) using logistic regression. We excluded adolescents already depressed at 15 years and adjusted for social class, maternal education, birth order, gender, alcohol intake and smoking. We repeated these analyses following multiple imputation for missing data.Results.In the sample with complete data (n = 2835), high and moderate GAD symptoms in adolescents not depressed at 15 years were associated with increased risk of depression at 18 years both in unadjusted analyses and adjusting for PD symptoms at 15 years and the above potential confounders. The adjusted odds ratio (OR) for depression at 18 years in adolescents with high relative to low GAD scores was 5.2 [95% confidence interval (CI) 3.0–9.1, overall p < 0.0001]. There were no associations between PD symptoms and depression at 18 years in any model (high relative to low PD scores, adjusted OR = 1.3, 95% CI 0.3–4.8, overall p = 0.737). Missing data imputation strengthened the relationship of GAD symptoms with depression (high relative to low GAD scores, OR = 6.2, 95% CI 3.9–9.9) but those for PD became weaker.Conclusions.Symptoms of GAD but not PD at 15 years are associated with depression at 18 years. Clinicians should be aware that adolescents with GAD symptoms may develop depression. [ABSTRACT FROM PUBLISHER]

BackgroundAlthough behavioural problems (e.g. anxiety, conduct, hyperactivity, peer problems) are known to be heritable both in early childhood and in adolescence, limited work has examined prediction across these ages, and none using a genetically informative sample.MethodWe examined, first, whether parental ratings of behavioural problems (indexed by the Strengths and Difficulties questionnaire) at ages 4, 7, 9, 12, and 16 years were stable across these ages. Second, we examined the extent to which stability reflected genetic or environmental effects through multivariate quantitative genetic analysis on data from a large (n > 3000) population (UK) sample of monozygotic and dizygotic twins.ResultsBehavioural problems in early childhood (age 4 years) showed significant associations with the corresponding behavioural problem at all subsequent ages. Moreover, stable genetic influences were observed across ages, indicating that biological bases underlying behavioural problems in adolescence are underpinned by genetic influences expressed as early as age 4 years. However, genetic and environmental innovations were also observed at each age.ConclusionThese observations indicate that genetic factors are important for understanding stable individual differences in behavioural problems across childhood and adolescence, although novel genetic influences also facilitate change in such behaviours. [ABSTRACT FROM PUBLISHER]

The article presents information on counter-urbanization process. The dominant theme in the redistribution of population in most developed countries during the past twenty years has been one of a decline in the population of major cities and metropolitan areas and a growth in medium and small-sized settlements and even remote rural areas, following decades of decline. In the debate over the causes and pervasiveness of the counter-urbanization process, the principal focus of attention has been upon its hierarchical and regional nature, within the context of a reduction in the comparative advantage enjoyed for so long by large cities and the emergence of a new spatial division of labor. The article tries to unrave how household turnover and in-migration selectivity are effecting rural change, and how local communities and policy-makers are responding to that change in a number of villages in East Northamptonshire, a rural district in the heart of "shire" England. A useful means of identifying the restructuring of a community's population from survey data is to sub-divide the contemporary population into mover and stayer households, since similarities and/or differences between the two groups can indicate the nature and direction of recent changes.

The article focuses on differences of rural and urban communities. The urbanization of rural communities has been viewed by sociologists and geographers alike within a rural-urban dichotomy. Traditionally it has been argued that there was a clear dichotomy between ways of life in an urban area as opposed to those of a rural area. Such differences in values, mores and behavior are explicable in terms of the influence of the particular environment. Social anthropologists have attempted to show that rural communities have a distinctively social life of their own. Such communities display closely-knit family and kinship networks a clear differentiation in the roles of husband and wife and a uniform value system. A number of studies within inner cities have revealed the existence of social characteristics akin to those usually associated with remote rural areas. The case study presents a typology of rural communities in north Herefordshire, England. Eleven indices of an economic, social and demographic character were chosen for classification.

There have been suggestions that some self-administered questionnaires designed to assess psychiatric disorder tend to overestimate prevalence in samples from Latin America. This phenomenon may be obscured when the General Health Questionnaire (GHQ) is used, as it is recommended that researchers determine the threshold in each setting by comparing the GHQ with a standardised interview. Reports in the literature suggest that Latin American samples have a higher threshold for case definition using the GHQ than that found in British samples. The present study confirmed this finding when comparing the 12-item GHQ in a Chilean primary care sample with a sample of primary care attenders from the United Kingdom. The increase in GHQ scores in the Chilean sample persisted after adjustment for age, sex, marital status and the score on the Revised Clinical Interview Schedule (CIS-R). The increase in scores seen in the Chilean sample was only found in that half of the GHQ that asks about negative aspects of mental health. [ABSTRACT FROM AUTHOR]

The article focuses on sudden death of people with mental illness who taking antipsychotic medical in Great Britain. To investigate the problem, the Royal College of Psychiatrists recommended a large-scale systematic study of the relationship between psychotropic drugs and sudden death. Psychiatrists throughout England and Wales will be asked to participate in the study.

Background: This study aims to understand the mechanisms contributing to the elevated risk of depression among sexual minority older adults compared to heterosexuals. Specifically, the role of loneliness as a potential mediator is investigated to inform targeted interventions for preventing depression in sexual minority populations., Methods: Data from the English Longitudinal Study of Ageing, focusing on adults aged over 50, were analysed. Sexual orientation (sexual minority or heterosexual) and loneliness scores (UCLA scale) were assessed at wave six (2010-2011), while depressive symptoms (CESD) were assessed at wave seven (2013-14). Linear regression models and mediation analyses, using g-computation formula and adjusted for confounders, were conducted., Results: The sample included 6794 participants, with 478 (7.0 %) identifying as sexual minorities. After adjustments, sexual minorities scored higher on depressive symptoms at wave seven (mean difference): 0.23, 95 % CI 0.07 to 0.39) and loneliness at wave six (MD: 0.27, 95 % CI 0.08 to 0.46). Loneliness was positively associated with depressive symptoms (coefficient: 0.27, 95 % CI 0.26 to 0.29). In mediation analyses, loneliness explained 15 % of the association between sexual orientation and subsequent depressive symptoms., Limitations: The dataset used sexual behaviour rather than desire and identity, potentially skewing representation of sexual minorities. Additionally, transgender older adults were not included due to limited gender diversity reported within the ELSA dataset., Conclusions: Loneliness appears to be a significant modifiable mechanism contributing to the heightened risk of depressive symptoms in sexual minority older adults compared with their heterosexual counterparts., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Maintenance antipsychotic medication is recommended for people with schizophrenia or recurrent psychosis, but the adverse effects are burdensome, and evidence on long-term outcomes is sparse. We aimed to assess the benefits and harms of a gradual process of antipsychotic reduction compared with maintenance treatment. Our hypothesis was that antipsychotic reduction would improve social functioning with a short-term increase in relapse., Methods: RADAR was an open, parallel-group, randomised trial done in 19 National Health Service Trusts in England. Participants were aged 18 years and older, had a diagnosis of recurrent, non-affective psychotic disorder, and were prescribed an antipsychotic. Exclusion criteria included people who had a mental health crisis or hospital admission in the past month, were considered to pose a serious risk to themselves or others by a treating clinician, or were mandated to take antipsychotic medication under the Mental Health Act. Through an independent, internet-based system, participants were randomly assigned (1:1) to gradual, flexible antipsychotic reduction, overseen by treating clinicians, or to maintenance. Participants and clinicians were aware of treatment allocations, but assessors were masked to them. Follow-up was for 2 years. Social functioning, assessed by the Social Functioning Scale, was the primary outcome. The principal secondary outcome was severe relapse, defined as requiring admission to hospital. Analysis was done blind to group identity using intention-to-treat data. The trial is completed and has been registered with ISRCTN registry (ISRCTN90298520) and with ClinicalTrials.gov (NCT03559426)., Findings: 4157 people were screened, of whom 253 were randomly allocated, including 168 (66%) men, 82 (32%) women, and 3 (1%) transgender people, with a mean age of 46 years (SD 12, range 22-79). 171 (67%) participants were White, 52 (21%) were Black, 16 (6%) were Asian, and 12 (5%) were of other ethnicity. The median dose reduction at any point during the trial was 67% in the reduction group and zero in the maintenance group; at 24 months it was 33% versus zero. At the 24-month follow-up, we assessed 90 of 126 people assigned to the antipsychotic dose reduction group and 94 of 127 assigned to the maintenance group, finding no difference in the Social Functioning Scale (β 0·19, 95% CI -1·94 to 2·33; p=0·86). There were 93 serious adverse events in the reduction group affecting 49 individuals, mainly comprising admission for a mental health relapse, and 64 in the maintenance group, relating to 29 individuals., Interpretation: At 2-year follow-up, a gradual, supported process of antipsychotic dose reduction had no effect on social functioning. Our data can help to inform decisions about the use of long-term antipsychotic medication., Funding: National Institute for Health Research., Competing Interests: Declaration of interests JM has grants from National Institute for Health Research (NIHR) and is a co-applicant on grants from the Medical Research Future Fund (MRFF) in Australia. She receives royalties from six books about psychiatric drugs, she has received lecture fees from Alberta Psychiatric Association, British Psychological Association, Universite de Sherbrooke, Case Western Reserve University, and University of Basal. She is co-chair person of the Critical Psychiatry Network and a board member of the Council for Evidence-based Psychiatry (both unpaid roles). RC is an unpaid Board Member of the International Institute for Psychiatric Drug Withdrawal (IIPDW), has undertaken paid work for the All Party Parliamentary Group for Prescribed Drug Dependence, and is a member of the Advisory Board for the PARTANE Study (a paid role). NF has grants from NIHR, Medical Research Council, Cure Parkinson's Trust, and the EU. He has received consulting fees from ALK, Sanofi Avantis, Gedeo Richter, Abbott, Galderma, Astra Zeneca, Ipsen, Vertex, Thea, Novo Nordisk, and Aimmune, speaker fees from Abbott Singapore, and been paid to sit on a data safety monitoring or advisory board by Orion. GL is chair of an NIHR-funded trial steering committee. SJ has grants from NIHR and UK Research and Innovation. She is chair of programme advisory committees for two studies funded through NIHR Programme Grants and has acted as a paid reviewer of grant applications for programmes on social interventions for Austrian foundation–Wiener Wissenschafts-, Forschungs- und Technologiefonds (Vienna Science and Technology Fund). TB is joint head of the Prescribing Observatory for Mental Health, Royal College of Psychiatrists. MH is co-applicant on grants from the MRFF in Australia, he has received consulting fees from Outro Health, a digital clinic aimed to support people to stop unnecessary antidepressants, lecture fees from National Health Service Trusts for grand rounds presentations, Salomon's University and University of Washington. He sits on the data safety monitoring board of the RELEASE trial in Australia, and is a co-founder of Outro Health. He is a member of the Critical Psychiatry Network and IIPDW (both unpaid roles). SP has grants from NIHR. All other authors declare no competing interests., (Copyright © 2023 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: It is unclear whether young people who attend higher education are at increased risk of common mental disorders, compared with those who do not attend. We aimed to investigate whether higher education attendance was associated with increased symptoms of common mental disorders (depression and anxiety) in young people before, during and after attendance., Methods: For this cohort study, we used two cohorts-the Longitudinal Studies of Young People in England (LSYPE1: N=4832, 55·8% [2696 of 4832] students; LSYPE2: n=6128, 50·7% [3104 of 6128] students), beginning in 2004 for LSYPE1 and 2013 for LSYPE2. Both cohorts were designed to be nationally representative, with schools in England as the primary sampling unit. Symptoms of common mental disorders were assessed with the General Health Questionnaire (GHQ-12) before (age 14-17 years for both cohorts), during (age 18-19 years for LSYPE2), and after (age 25 years for LSYPE1) higher education. We assessed differences in GHQ scores using unadjusted and confounder adjusted linear regression., Findings: At ages 18-19 years (LSYPE2), mean GHQ-12 scores were 12·0 (SD 6·4) among students and 11·6 (SD 6·8) among non-students (adjusted mean difference 0·36, 95% CI 0·05 to 0·68; p=0·024). In LSYPE1, young people who attended higher education at ages 18-20 years had higher symptoms of common mental disorders at ages 16-17 years than those who did not (0·60, 0·30 to 0·90). However, after higher education (age 25 years for LSYPE1), there was no evidence of a difference-mean GHQ-12 scores were 11·4 (SD 5·5) among those who had attended and 11·7 (SD 6·4) among those who had not attended (-0·25, -0·66 to 0·16; p=0·23)., Interpretation: We found evidence that students had more symptoms of common mental disorders than non-students at ages 18-19 years, albeit the effect size was small and there was no evidence of a longer-term difference at the age of 25 years., Funding: Department for Education., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 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: The role of alcohol use in the development of depression is unclear. We aimed to investigate whether alcohol dependence, but not high frequency or quantity of consumption, during adolescence increased the risk of depression in young adulthood., Methods: In this prospective cohort study, we included adolescents who were born to women recruited to the Avon Longitudinal Study of Parents and Children in Avon, UK, with delivery dates between April 1, 1991, and Dec 31, 1992. Alcohol dependence and consumption were measured at about age 16 years, 18 years, 19 years, 21 years, and 23 years using the self-reported Alcohol Use Disorders Identification Test, and at about age 18 years, 21 years, and 23 years using items corresponding to DSM-IV symptoms. The primary outcome was depression at age 24 years, assessed using the Clinical Interview Schedule Revised. Analyses were probit regressions between growth factors for alcohol dependence and consumption and depression, before and after adjustments for confounders: sex, housing tenure, maternal education, maternal depressive symptoms, parents' alcohol use, conduct problems at age 4 years, being bullied from age 12-16 years, and frequency of smoking cigarettes or cannabis. Adolescents were included in analyses if they had data from at least one timepoint for alcohol use and confounders., Findings: We included 3902 adolescents (2264 [58·0%] female; 1638 [42·0%] male) in our analysis, and 3727 (96·7%) of 3853 participants with data on ethnicity were White. After adjustments, we found a positive association between alcohol dependence at 18 years of age (latent intercept) and depression at 24 years of age (probit coefficient 0·13 [95% CI 0·02 to 0·25]; p=0·019), but no association between rate of change (linear slope) and depression (0·10 [-0·82 to 1·01]; p=0·84). There was no evidence of an association between alcohol consumption and depression (latent intercept probit coefficient -0·01 [-0·06 to 0·03]; p=0·60; linear slope 0·01 [-0·40 to 0·42]; p=0·96) after adjustments., Interpretation: Psychosocial or behavioural interventions that reduce the risk of alcohol dependence during adolescence could contribute to preventing depression in young adulthood., Funding: UK Medical Research Council and Alcohol Research UK (grant number MR/L022206/1)., Competing Interests: Declaration of interests MH has served as Trustee of Society of Study of Addiction and Regional Editor of Addiction in the past 3 years. All other authors declare no competing interests., (Copyright © 2023 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.)

Introduction: We investigated the incidence of diagnosed dementia and whether age at diagnosis and survival afterward differs among the United Kingdom's three largest ethnic groups., Methods: We used primary care electronic health records, linked Hospital Episode Statistics and mortality data for adults aged ≥65 years. We compared recorded dementia incidence 1997-2018, age at diagnosis, survival time and age at death after diagnosis in White, South Asian, and Black people., Results: Dementia incidence was higher in Black people (incidence rate ratios [IRR] 1.22, 95% CI 1.15-1.30). South Asian and Black people with dementia had a younger age of death than White participants (mean difference for South Asian participants -2.97 years, (95% CI -3.41 to -2.53); and Black participants -2.66 years, (95% CI -3.08 to -2.24)., Discussion: South Asian and Black peoples' younger age of diagnosis and death means targeted prevention and care strategies for these groups should be prioritized and tailored to facilitate take-up., (© 2022 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Purpose: Lack of social support is considered a potential risk factor for postnatal depression but limited longitudinal evidence is available. Pregnancy, when women have increased contact with healthcare services, may be an opportune time to intervene and help strengthen women's social networks to prevent feelings of depression postnatally, particularly for those at greatest risk. Our study examined the longitudinal relationship between social support in pregnancy and postnatal depression, and whether this is moderated by age or relationship status., Methods: We analysed data collected from 525 women from a diverse inner-city maternity population in England who were interviewed in pregnancy and again three months postnatally. Women provided sociodemographic information and completed self-report measures of depression (Edinburgh Postnatal Depression Scale) and social support (Social Provisions Scale)., Results: Less social support in pregnancy was associated with postnatal depression, after adjusting for sociodemographic confounders and antenatal depression (Coef. = - 0.05; 95% CI - 0.10 to - 0.01; p = 0.02). There was weak evidence of a moderating effect of relationship status. Subgroup analysis showed a stronger relationship between social support in pregnancy and postnatal depression for women who were not living with a partner (Coef. =  - 0.11; 95% CI - 0.21 to - 0.01; p = 0.03) than for those who were (Coef. =  - 0.03; 95% CI - 0.09 to 0.02; p = 0.28). Sensitivity analysis using multiple imputations to account for missing data confirmed the main results., Conclusions: Interventions that target social support in pregnancy have the potential to reduce depression postnatally. Future research should explore in greater detail which women would benefit most from which type of social support., (© 2022. The Author(s).)

Background: Depression is a common mental health condition with considerable negative impact on health and well-being. Although antidepressants are recommended as first-line treatment, there is limited evidence regarding the cost effectiveness of long-term maintenance antidepressants for preventing relapse., Objectives: Our objective was to calculate the mean incremental costs and quality-adjusted life-years (QALYs) over 12 months of discontinuing long-term antidepressant medication in well patients compared with maintenance, using patient-level trial data., Methods: We conducted a cost-utility analysis of 478 participants from 150 UK general practices recruited to a randomised, double-blind trial (ANTLER). QALYs were calculated from EQ-5D-5L and 12-Item Short Form survey (SF-12) results, with primary analysis using the EQ-5D-5L value set for England. Resource use was collected from primary care patient electronic medical records and self-completed questionnaires capturing mental-health-related resource use. Costs were calculated by applying standard UK unit costs to resource use. Adjustments were made for baseline variables., Results: Participants randomised to discontinuation had significantly worse utility scores at 3 months (- 0.032; 95% confidence interval [CI] - 0.053 to - 0.011) but no significant difference in QALYs (- 0.011; 95% CI - 0.026 to 0.003) or costs (£3.11; 95% CI - 41.28 to 47.50) at 12 months. The probability that discontinuation was cost effective compared with maintenance was 12.9% at a threshold of £20,000 per QALY gained., Conclusions: Discontinuation of antidepressants was unlikely to be cost effective compared with maintenance for currently well patients on long-term antidepressants. However, this analysis provides no information on the wider impact of antidepressants. Our findings provide information on the potential impact of discontinuing long-term maintenance antidepressants and facilitate improving guidance for shared patient-clinician decision making., Trial Registration: EudraCT number 2015-004210-26; ISRCTN number ISRCTN15969819., (© 2021. The Author(s).)

Background: The number of antipsychotic prescriptions dispensed annually in England has increased substantially over the past decade. It is not known whether this is due to changes in prescribing practices, or an increase in the prevalence of psychosis. To our knowledge, no previous studies have investigated temporal trends in prevalence of psychotic symptoms in non-clinical populations., Methods: We used data from the nationally representative Adult Psychiatric Morbidity Surveys 2000, 2007 and 2014 to (1) test whether the prevalence of psychotic symptoms increased between 2000 and 2014; (2) compare prevalence of psychotic symptoms to the prevalence of being prescribed antipsychotic medication; and (3) identify correlates of experiencing psychotic symptoms., Results: There was a small increase in the prevalence of psychotic symptoms in 2014 compared to 2000 (prevalence in 2000 5.6%, 95% confidence intervals (CI) 5.1% to 6.2%; prevalence in 2014 6.8%, 95% CI 6.1% - 7.6%). This corresponded to an adjusted odds ratio of 1.2 (95% CI 1.02-1.40, p=0.026) for experiencing psychotic symptoms in 2014 compared to 2007. By comparison, antipsychotic medication use doubled over this period (prevalence in 2000 0.6%, 95% CI 0.4%-0.7%; prevalence in 2014 1.2% 95% CI 0.9%-1.5%; aOR 2.22 (1.52-3.25) p<0.001). Correlates of reporting psychotic symptoms included ethnic minority identity, younger age, lower social class, alcohol and cannabis use, and any psychiatric diagnosis., Conclusions: While the rates of antipsychotic prescription doubled between 2000 and 2014, the odds of having psychotic symptoms rose only slightly. The reasons for this warrant further investigation., Competing Interests: Declaration of competing interest None., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Loneliness is experienced by a third of older adults in the UK and is a modifiable potential risk factor for depressive symptoms. It is unclear how the association between loneliness and depressive symptoms persists over time, and whether it is independent of related social constructs and genetic confounders. We aimed to investigate the association between loneliness and depressive symptoms, assessed on multiple occasions during 12 years of follow-up, in a large, nationally representative cohort of adults aged 50 years and older in England., Methods: We did a longitudinal study using seven waves of data that were collected once every 2 years between 2004 and 2017, from adults aged 50 years and older in the English Longitudinal Study of Ageing (ELSA). The exposure was loneliness at baseline (wave two), measured with the short 1980 revision of the University of California, Los Angeles Loneliness Scale (R-UCLA). The primary outcome was a score indicating severity of depression measured at six subsequent timepoints (waves three to eight), using the eight-item version of the Centre for Epidemiologic Studies Depression Scale (CES-D). Analyses were linear multilevel regressions, before and after adjusting for social isolation, social support, polygenic risk scores, and other sociodemographic and health-related confounders. The secondary outcome was depression diagnosis, measured using a binary version of the CES-D., Findings: 4211 (46%) of 9171 eligible participants had complete data on exposure, outcome, and confounders, and were included in our complete case sample. After all adjustments, a 1-point increase in loneliness score was associated with a 0·16 (95% CI 0·13-0·19) increase in depressive symptom severity score (averaged across all follow-ups). We estimated a population attributable fraction for depression associated with loneliness of 18% (95% CI 12-24) at 1 year of follow-up and 11% (3-19) at the final follow-up (wave eight), suggesting that 11-18% of cases of depression could potentially be prevented if loneliness were eliminated. Associations between loneliness and depressive symptoms remained after 12 years of follow-up, although effect sizes were smaller with longer follow-up., Interpretation: Irrespective of other social experiences, higher loneliness scores at baseline were associated with higher depression symptom severity scores during 12 years of follow-up among adults aged 50 years and older. Interventions that reduce loneliness could prevent or reduce depression in older adults, which presents a growing public health problem worldwide., Funding: National Institute on Aging and a consortium of UK Government departments coordinated by the National Institute for Health Research., (Copyright © 2021 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: Around one in ten adults take antidepressants for depression in England, and their long-term use is increasing. Some need them to prevent relapse, but 30-50% could possibly stop them without relapsing and avoid adverse effects and complications of long-term use. However, stopping is not always easy due to withdrawal symptoms and a fear of relapse of depression. When general practitioners review patients on long-term antidepressants and recommend to those who are suitable to stop the medication, only 6-8% are able to stop. The Reviewing long-term antidepressant use by careful monitoring in everyday practice (REDUCE) research programme aims to identify safe and cost-effective ways of helping patients taking long-term antidepressants taper off treatment when appropriate., Methods: Design: REDUCE is a two-arm, 1:1 parallel group randomised controlled trial, with randomisation clustered by participating family practices., Setting: England and north Wales., Population: patients taking antidepressants for longer than 1 year for a first episode of depression or longer than 2 years for repeated episodes of depression who are no longer depressed and want to try to taper off their antidepressant use., Intervention: provision of 'ADvisor' internet programmes to general practitioners or nurse practitioners and to patients designed to support antidepressant withdrawal, plus three patient telephone calls from a psychological wellbeing practitioner. The control arm receives usual care. Blinding of patients, practitioners and researchers is not possible in an open pragmatic trial, but statistical and health economic data analysts will remain blind to allocation., Outcome Measures: the primary outcome is self-reported nine-item Patient Health Questionnaire at 6 months for depressive symptoms., Secondary Outcomes: depressive symptoms at other follow-up time points, anxiety, discontinuation of antidepressants, social functioning, wellbeing, enablement, quality of life, satisfaction, and use of health services for costs., Sample Size: 402 patients (201 intervention and 201 controls) from 134 general practices recruited over 15-18 months, and followed-up at 3, 6, 9 and 12 months. A qualitative process evaluation will be conducted through interviews with 15-20 patients and 15-20 practitioners in each arm to explore why the interventions were effective or not, depending on the results., Discussion: Helping patients reduce and stop antidepressants is often challenging for practitioners and time-consuming for very busy primary care practices. If REDUCE provides evidence showing that access to internet and telephone support enables more patients to stop treatment without increasing depression we will try to implement the intervention throughout the National Health Service, publishing practical guidance for professionals and advice for patients to follow, publicised through patient support groups., Trial Registration: ISRCTN:12417565. Registered on 7 October 2019.

Background: Evidence exists that maternal depression in the perinatal period has an adverse effect on a range of early childhood outcomes and increases the risk of offspring depression during adolescence. However, the association between maternal depression during the perinatal period and offspring psychotic experiences has not been investigated. We aimed to investigate whether there is an association between maternal antenatal or postnatal depression and offspring psychotic experiences at 18 years of age., Methods: This longitudinal study used data from the Avon Longitudinal Study of Parents and Children (ALSPAC), a prospective birth cohort, which recruited 14 541 pregnant women with an estimated delivery date between April 1, 1991, and Dec 31, 1992. Perinatal depression was measured using the Edinburgh Postnatal Depression Scale (EPDS); offspring psychotic experiences at 18 years of age were measured using the Psychosis-Like Symptom Interview. Offspring of mothers with complete data on maternal perinatal depression measures, and complete data on outcome (psychotic experiences) and confounding variables were included in the main analysis. For the main analysis, we used logistic regression to examine the associations between maternal depression (antenatal and postnatal) and offspring psychotic experiences at the age of 18 years. We used biprobit regression to model the association between maternal antenatal depression and the two offspring outcomes (psychotic experiences and depression) at 18 years of age jointly., Findings: 3067 offspring for whom data were available on maternal perinatal depression and offspring psychotic experiences aged 18 years were included in analyses. Maternal antenatal depressive symptoms were associated with offspring psychotic experiences at 18 years of age, with an unadjusted odds ratio (OR) of 1·38 (95% CI 1·18-1·61, p=0·0001) and after adjustment for confounders, an OR of 1·26 (1·06-1·49, p=0·0074). Maternal antenatal depressive symptoms were associated with both offspring psychotic experiences at the age of 18 years (n=2830, OR for a 5-point increase in EPDS score: 1·32 [95% CI 1·16-1·51], p<0·0001) and offspring depression at 18 years (OR for a 5-point increase in EPDS score: 1·18 [1·03-1·34], p=0·016). From joint modelling, there was no evidence that the association between maternal antenatal depression and offspring psychotic experiences differed in strength compared with offspring depression (p=0·19)., Interpretation: The offspring of mothers who experience depression in the perinatal period are more likely to report psychotic experiences at 18 years of age. If the association is found to be causal, it would strengthen the case for identifying and treating maternal depression during and after pregnancy., Funding: UK Medical Research Council and the Wellcome Trust., (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.)

There is little research on the role of school and its composition in explaining individual children's psychological outcomes. This study examined for the first time the role of several primary-school compositional characteristics, and their interactions with individual level characteristics, in the development of two such outcomes, internalising and externalising problems, at ages 7, 11 and 14 years in 4794 children in England participating in the Millennium Cohort Study. Using hierarchical (multilevel) linear models, we found that, even after adjusting for individual and family characteristics, children in schools with higher proportions of pupils eligible for free school meals had more externalising problems. In general, children with special educational needs, lower academic performance, more distressed mothers, and those in non-intact families had more internalising and externalising problems. Our results underline the importance of targeting schools with less affluent overall intakes, but also highlight the key role of individual and family characteristics in the development of their pupils' psychological functioning.

Aim: To investigate factors influencing diagnostic discordance for non-diabetic hyperglycaemia and Type 2 diabetes., Methods: Some 10 000 adults at increased risk of diabetes were screened with HbA 1c and fasting plasma glucose (FPG). The 2208 participants with initial HbA 1c ≥ 42 mmol/mol (≥ 6.0%) or FPG ≥ 6.1 mmol/l were retested after a median 40 days. We compared the first and second HbA 1c results, and consequent diagnoses of non-diabetic hyperglycaemia and Type 2 diabetes, and investigated predictors of discordant diagnoses., Results: Of 1463 participants with non-diabetic hyperglycaemia and 394 with Type 2 diabetes on first testing, 28.4% and 21.1% respectively had discordant diagnoses on repeated testing. Initial diagnosis of non-diabetic hyperglycaemia and/or impaired fasting glucose according to both HbA 1c and FPG criteria, or to FPG only, made reclassification as Type 2 diabetes more likely than initial classification according to HbA 1c alone. Initial diagnosis of Type 2 diabetes according to both HbA 1c and FPG criteria made reclassification much less likely than initial classification according to HbA 1c alone. Age, and anthropometric and biological measurements independently but inconsistently predicted discordant diagnoses and changes in HbA 1c ., Conclusions: Diagnosis of non-diabetic hyperglycaemia or Type 2 diabetes with a single measurement of HbA 1c in a screening programme for entry to diabetes prevention trials is unreliable. Diagnosis of non-diabetic hyperglycaemia and Type 2 diabetes should be confirmed by repeat testing. FPG results could help prioritise retesting. These findings do not apply to people classified as normal on a single test, who were not retested., (© 2019 Diabetes UK.)

Background: Depressive symptoms and inflammation are risk factors for cardiovascular disease (CVD) and mortality. We investigated the combined association of these factors with the prediction of CVD and all-cause mortality in a representative cohort of older men and women., Methods: We measured C-reactive protein (CRP) and depressive symptoms in 5328 men and women aged 52-89 years in the English Longitudinal Study of Ageing. Depressive symptoms were measured using the eight-item Centre for Epidemiological Studies Depression Scale. CRP was analysed from peripheral blood. Mortality was ascertained from national registers and associations with depressive symptoms and inflammation were estimated using Cox proportional hazard models., Results: We identified 112 CVD related deaths out of 420 all-cause deaths in men and 109 CVD related deaths out of 334 all-cause deaths in women over a mean follow-up of 7.7 years. Men with both depressive symptoms and high CRP (3-20 mg/L) had an increased risk of CVD mortality (hazard ratio; 95% confidence interval: 3.89; 2.04-7.44) and all-cause mortality (2.40; 1.65-3.48) after adjusting for age, socioeconomic variables and health behaviours. This considerably exceeds the risks associated with high CRP alone (CVD 2.43; 1.59-3.71, all-cause 1.49; 1.20-1.84). There was no significant increase in mortality risk associated with depressive symptoms alone in men. In women, neither depressive symptoms or inflammation alone or the combination of both significantly predicted CVD or all-cause mortality., Conclusions: The combination of depressive symptoms and increased inflammation confers a considerable increase in CVD mortality risk for men. These effects appear to be independent, suggesting an additive role.

Hospitalisation of people with dementia is associated with adverse outcomes and high costs. We aimed to examine general, i.e. non-psychiatric, hospitalisation rates, changes since 2008 and factors associated with admission. We also aimed to compare admission rates of people with dementia with age-matched people without dementia. We conducted a cohort study of adults ≥ 65 years, with dementia diagnosed during the 2008-2016 study window, derived from a large secondary mental healthcare database in South London, UK. We used national general hospital records to identify emergency and elective hospitalisations. We calculated the cumulative incidence and rate of hospitalisation and examined predictors of hospitalisation using negative binomial regression, with multiple imputation for missing covariate data. We calculated age-standardised admission ratio for people with dementia compared to those without. Of 10,137 people, 50.6% were admitted to hospital in the year following dementia diagnosis and 75.9% were admitted during median 2.5 years follow-up. Annual admission rate was 1.26/person-year of which 0.90/person-year were in emergency. Emergency hospitalisation rate increased throughout the study period. Compared to controls without diagnosed dementia in the catchment area, the age-standardised emergency admission ratio for people with dementia was 2.06 (95% CI 1.95, 2.18). Male, older, white and socio-economically deprived people and those with clinically significant comorbid physical illness, depressed mood, activity of daily living or living condition problems had more hospitalisations. Emergency hospitalisations of people with dementia are higher than those without, and increasing. Many factors associated with admission are social and psychological, and may be targets for future interventions that aim to reduce avoidable admissions.

Background: Low-grade inflammation is associated with depression, but studies of specific symptoms are relatively scarce. Association between inflammatory markers and specific symptoms may provide insights into potential mechanism of inflammation-related depression. Using longitudinal data, we have tested whether childhood serum interleukin 6 (IL-6) and C-reactive protein (CRP) levels are associated with specific depressive symptoms in early adulthood., Methods: In the ALSPAC birth cohort, serum IL-6 and CRP levels were assessed at age 9 years and 19 depressive symptoms were assessed at age 18 years. We used modified Poisson generalised linear regression with robust error variance to estimate the risk ratio (RR) and 95% confidence interval (95% CI) for each depressive symptom. In addition, we used confirmatory factor analysis to create two continuous latent variables representing somatic/neurovegetative and psychological dimension scores. Structural equation modelling was used to test the associations between IL-6 and these dimension scores., Results: Based on data from 2731 participants, IL-6 was associated with diurnal mood variation, concentration difficulties, fatigue and sleep disturbances. The adjusted RRs for these symptoms at age 18 years for participants in top, compared with bottom, third of IL-6 at age 9 years were 1.75 (95% CI, 1.13-2.69) for diurnal mood variation, 1.50 (95% CI, 1.11-2.02) for concentration difficulties, 1.31 (95% CI, 1.12-1.54) for fatigue, and 1.24 (95% CI, 1.01-1.52) for sleep disturbances. At dimension level, IL-6 was associated with both somatic/neurovegetative (β = 0.059, SE = 0.024, P = 0.013) and psychological (β = 0.056, SE = 0.023, P = 0.016) scores., Conclusions: Inflammation is associated with specific symptoms of depression. Associations with so-called somatic/neurovegetative symptoms of depression such as fatigue, sleep disturbances and diurnal mood variation indicate that these symptoms could be useful treatment targets and markers of treatment response in clinical trials of anti-inflammatory treatment for depression., (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: Recognizing dementia in general hospitals allows for tailored care. We aimed to assess hospital dementia diagnosis accuracy, changes over time, and predictors of correct identification., Method: Retrospective cohort study of people over 65 years, using data from a large mental health care database as gold standard, linked to 2008-2016 English hospital data., Results: In 21,387 people who had 138,455 admissions, we found sensitivity and specificity of dementia recording, respectively, to be 78.0% and 92.0% for each person's complete records, and 63.3% and 96.6% for each nonelective admission. Diagnostic sensitivity increased between 2008 and 16. Accurate general hospital recording of the presence of dementia was lower in ethnic minority groups, younger, single people, and those with physical illness., Discussion: Dementia diagnosis recording in general hospitals is increasing but remains less likely in some groups. Clinicians should be aware of this inequity and have a higher index of clinical suspicion in these groups., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: To identify developmental sub-groups of depressive symptoms during the second decade of life, a critical period of brain development, using data from a prospective birth cohort. To test whether childhood intelligence and inflammatory markers are associated with subsequent persistent depressive symptoms., Methods: IQ, a proxy for neurodevelopment, was measured at age 8 years. Interleukin 6 (IL-6) and C-reactive protein, typical inflammatory markers, were measured at age 9 years. Depressive symptoms were measured six times between 10 and 19 years using the short mood and feelings questionnaire (SMFQ), which were coded as binary variable and then used in latent class analysis to identify developmental sub-groups of depressive symptoms., Results: Longitudinal SMFQ data from 9156 participants yielded three distinct population sub-groups of depressive symptoms: no symptoms (81.2%); adolescent-onset symptoms (13.2%); persistent symptoms (5.6%). Lower IQ and higher IL-6 levels in childhood were independently associated with subsequent persistent depressive symptoms in a linear, dose-response fashion, but not with adolescent-onset symptoms. Compared with the group with no symptoms the adjusted odds ratio for persistent depressive symptoms per s.d. increase in IQ was 0.80 (95% CI, 0.68-0.95); that for IL-6 was 1.20 (95% CI, 1.03-1.39). Evidence for an association with IL-6 remained after controlling for initial severity of depressive symptoms at 10 years. There was no evidence that IL-6 moderated or mediated the IQ-persistent depressive symptom relationship., Conclusions: The results indicate potentially important roles for two distinct biological processes, neurodevelopment and inflammation, in the aetiology of persistent depressive symptoms in young people.

Importance: Most patients with psychotic disorders experience severe cognitive impairment, but the onset and course of this impairment remain unclear. Moreover, the course of cognitive functions in other psychiatric conditions remains largely unexamined., Objective: To chart the course of general and specific cognitive functions in individuals with psychotic disorders, psychotic experiences, and depression., Design, Setting, and Participants: The Avon Longitudinal Study of Parents and Children (ALSPAC) is a prospective cohort study comprising all live births between April 1, 1991, and December 31, 1992, in Avon, England. The dates of analysis were September 2015 to July 2016. Participants who underwent cognitive testing at ages 18 months and 4, 8, 15, and 20 years and psychiatric assessment at age 18 years were included., Main Outcomes and Measures: Individuals with psychotic disorder, psychosis with depression, psychotic experiences, and depression were compared with controls. Outcomes were full-scale, verbal, and nonverbal IQ at ages 18 months and 4, 8, 15, and 20 years, as well as measures of processing speed, working memory, language, visuospatial ability, and attention at ages 8 and 20 years., Results: The following numbers of individuals were available for analyses in this longitudinal birth cohort study: 511 (238 male [46.6%]) at age 18 months (mean [SD] age, 1.53 [0.03] years), 483 (229 male [47.4%]) at age 4 years (mean [SD] age, 4.07 [0.03] years), 3930 (1679 male [42.7%]) at age 8 years (mean [SD] age, 8.65 [0.29] years), 3783 (1686 male [44.6%]) at age 15 years (mean [SD] age, 15.45 [0.27] years), and 257 (90 male [35.0%]) at age 20 years (mean [SD] age, 20.06 [0.55] years). Individuals with psychotic disorder showed continually increasing deficits between infancy (18 months) and adulthood (20 years) in full-scale IQ (effect size of change [ESΔ] = -1.09, P = .02) and nonverbal IQ (ESΔ = -0.94, P = .008). The depression group showed a small, increasing deficit in nonverbal IQ (ESΔ = -0.29, P = .04) between infancy and adulthood. Between ages 8 and 20 years, the psychotic disorder group exhibited developmental lags (ie, slower growth) in measures of processing speed (ESΔ = -0.68, P = .001), working memory (ESΔ = -0.59, P = .004), and attention (ESΔ = -0.44, P = .001) and large, static deficits in measures of language (ES = -0.87, P = .005) and visuospatial ability (ES = -0.90, P = .001). There was only weak evidence for cognitive deficits in the psychosis with depression group and the psychotic experiences group., Conclusions and Relevance: The findings herein suggest that the origins of psychotic disorder involve dynamic developmental processes, affecting both verbal and nonverbal abilities throughout the first 2 decades of life and leading to increasing dysfunction. These developmental processes do not manifest in other psychiatric disorders, such as psychosis with depression and depression.

A link between infection, inflammation, neurodevelopment and adult illnesses has been proposed. The objective of this study was to examine the association between infection burden during childhood - a critical period of development for the immune and nervous systems - and subsequent systemic inflammatory markers and general intelligence. In the Avon Longitudinal Study of Parents and Children, a prospective birth cohort in England, we examined the association of exposure to infections during childhood, assessed at seven follow-ups between age 1·5 and 7·5 years, with subsequent: (1) serum interleukin 6 and C-reactive protein (CRP) levels at age 9; (2) intelligence quotient (IQ) at age 8. We also examined the relationship between inflammatory markers and IQ. Very high infection burden (90+ percentile) was associated with higher CRP levels, but this relationship was explained by body mass index (adjusted odds ratio (OR) 1·19; 95% confidence interval (CI) 0·95-1·50), maternal occupation (adjusted OR 1·23; 95% CI 0·98-1·55) and atopic disorders (adjusted OR 1·24; 95% CI 0·98-1·55). Higher CRP levels were associated with lower IQ; adjusted β = -0·79 (95% CI -1·31 to -0·27); P = 0·003. There was no strong evidence for an association between infection and IQ. The findings indicate that childhood infections do not have an independent, lasting effect on circulating inflammatory marker levels subsequently in childhood; however, elevated inflammatory markers may be harmful for intellectual development/function.

Objective: To investigate the strength of the association between victimisation by peers at age 13 years and depression at 18 years., Design: Longitudinal observational study., Setting: Avon Longitudinal Study of Parents and Children, a UK community based birth cohort., Participants: 6719 participants who reported on peer victimisation at age 13 years., Main Outcome Measures: Depression defined according to international classification of diseases, 10th revision (ICD-10) criteria, assessed using the clinical interview schedule-revised during clinic assessments with participants when they were aged 18 years. 3898 participants had data on both victimisation by peers at age 13 years and depression at age 18 years., Results: Of the 683 participants who reported frequent victimisation at age 13 years, 101 (14.8%) were depressed according to ICD-10 criteria at 18 years; of the 1446 participants reporting some victimisation at age 13 years, 103 (7.1%) were depressed at age 18 years; and of the 1769 participants reporting no victimisation at age 13 years, 98 (5.5%) were depressed at age 18 years. Compared with children who were not victimised those who were frequently victimised by peers had over a twofold increase in odds of depression (odds ratio 2.96, 95% confidence interval 2.21 to 3.97, P<0.001). This association was slightly reduced when adjusting for confounders (2.32, 1.49 to 3.63, P<0.001). The population attributable fraction suggested that 29.2% (95% confidence interval 10.9% to 43.7%) of depression at age 18 years could be explained by peer victimisation if this were a causal relation., Conclusion: When using observational data it is impossible to be certain that associations are causal. However, our results are consistent with the hypothesis that victimisation by peers in adolescence is associated with an increase in the risk of developing depression as an adult., (© Bowes et al 2015.)

Background: Psychotic phenomena are common in the general population but are excluded from diagnostic criteria for mild to moderate depression and anxiety despite their co-occurrence and shared risk factors. We used item response theory modelling to examine whether the co-occurrence of depressive, anxiety and psychotic phenomena is best explained by: (1) a single underlying factor; (2) two separate, uncorrelated factors; (3) two separate yet linked factors; or (4) two separate domains along with an underlying 'common mental distress' (CMD) factor. We defined where, along any latent continuum, the psychopathological items contributed most information., Method: We performed a secondary analysis of cross-sectional, item-level information from measures of depression, anxiety and psychotic experiences in 6617 participants aged 13 years from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort and 977 participants aged 18 years from the ROOTS schools-based sample. We replicated results from one sample in the other and validated the latent factors against an earlier parental measure of mental state., Results: In both cohorts depression, anxiety and psychotic items were best represented as a bi-factor model with a single, unitary CMD factor on which psychotic items conveyed information about the more severe end (model 4); residual variation remained for psychotic items. The CMD factor was significantly associated with the prior parental measure., Conclusions: Psychotic phenomena co-occur with depression and anxiety in teenagers and may be a marker of severity in a single, unitary dimension of CMD. Psychotic phenomena should be routinely included in epidemiological assessments of psychiatric morbidity, otherwise the most severe symptomatology remains unmeasured.

Background: Schizophrenia has a neurodevelopmental component to its origin, and may share overlapping pathogenic mechanisms with childhood neurodevelopmental disorders (NDs). Nevertheless, longitudinal studies of psychotic outcomes among individuals with NDs are limited. We report a population-based prospective study of six common childhood NDs, subsequent neurocognitive performance and the risk of psychotic experiences (PEs) in early adolescence., Method: PEs were assessed by semi-structured interviews at age 13 years. IQ and working memory were measured between ages 9 and 11 years. The presence of six NDs (autism spectrum, dyslexia, dyspraxia, dysgraphia, dysorthographia, dyscalculia) was determined from parent-completed questionnaires at age 9 years. Linear regression calculated the mean difference in cognitive scores between children with and without NDs. Associations between NDs and PEs were expressed as odds ratios (ORs) with 95% confidence intervals (CIs); effects of cognitive deficits were examined. Potential confounders included age, gender, father's social class, ethnicity and maternal education., Results: Out of 8220 children, 487 (5.9%) were reported to have NDs at age 9 years. Children with, compared with those without, NDs performed worse on all cognitive measures; the adjusted mean difference in total IQ was 6.84 (95% CI 5.00-8.69). The association between total IQ and NDs was linear (p < 0.0001). The risk of PEs was higher in those with, compared with those without, NDs; the adjusted OR for definite PEs was 1.76 (95% CI 1.11-2.79). IQ (but not working memory) deficit partly explained this association., Conclusions: Higher risk of PEs in early adolescence among individuals with childhood ND is consistent with the neurodevelopmental hypothesis of schizophrenia.

Psychotic experiences are not uncommon in general population samples, but no studies have examined to what extent confirmed risk variants for schizophrenia are associated with such experiences. A total of 3483 children in a birth cohort study participated in semistructured interviews for psychotic experiences at ages 12 and 18. We examined whether (1) a composite measure of risk for schizophrenia conferred by common alleles (polygenic score) was associated with psychotic experiences, (2) variants with genome-wide evidence for association with schizophrenia were associated with psychotic experiences, and (3) we could identify genetic variants for psychotic experiences using a genome-wide association (GWA) approach. We found no evidence that a schizophrenia polygenic score, or variants showing genome-wide evidence of association with schizophrenia, were associated with adolescent psychotic experiences within the general population. In fact, individuals who had a higher number of risk alleles for genome-wide hits for schizophrenia showed a decreased risk of psychotic experiences. In the GWA study, no variants showed GWA for psychotic experiences, and there was no evidence that the strongest hits (P < 5 × 10(-5)) were enriched for variants associated with schizophrenia in large consortia. Although polygenic scores are weak tools for prediction of schizophrenia, they show strong evidence of association with this disorder. Our findings, however, lend little support to the hypothesis that psychotic experiences in population-based samples of adolescents share a comparable genetic architecture to schizophrenia, or that utilizing a broader and more common phenotype of psychotic experiences will be an efficient approach to increase understanding of the genetic etiology of schizophrenia., (© The Author 2013. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.)

Importance: Longitudinal studies have linked the systemic inflammatory markers interleukin 6 (IL-6) and C-reactive protein (CRP) with the risk of developing heart disease and diabetes mellitus, which are common comorbidities for depression and psychosis. Recent meta-analyses of cross-sectional studies have reported increased serum levels of these inflammatory markers in depression, first-episode psychosis, and acute psychotic relapse; however, the direction of the association has been unclear., Objective: To test the hypothesis that higher serum levels of IL-6 and CRP in childhood would increase future risks for depression and psychosis., Design, Setting, and Participants: The Avon Longitudinal Study of Parents and Children (ALSPAC)is a prospective general population birth cohort study based in Avon County, England. We have studied a subsample of approximately 4500 individuals from the cohort with data on childhood IL-6 and CRP levels and later psychiatric assessments., Measurement of Exposure: Levels of IL-6 and CRP were measured in nonfasting blood samples obtained in participants at age 9 years., Main Outcomes and Measures: Participants were assessed at age 18 years. Depression was measured using the Clinical Interview Schedule-Revised (CIS-R) and Mood and Feelings Questionnaire (MFQ), thus allowing internal replication; psychotic experiences (PEs) and psychotic disorder were measured by a semistructured interview., Results: After adjusting for sex, age, body mass index, ethnicity, social class, past psychological and behavioral problems, and maternal postpartum depression, participants in the top third of IL-6 values compared with the bottom third at age 9 years were more likely to be depressed (CIS-R) at age 18 years (adjusted odds ratio [OR], 1.55; 95% CI, 1.13-2.14). Results using the MFQ were similar. Risks of PEs and of psychotic disorder at age 18 years were also increased with higher IL-6 levels at baseline (adjusted OR, 1.81; 95% CI, 1.01-3.28; and adjusted OR, 2.40; 95% CI, 0.88-6.22, respectively). Higher IL-6 levels in childhood were associated with subsequent risks of depression and PEs in a dose-dependent manner., Conclusions and Relevance: Higher levels of the systemic inflammatory marker IL-6 in childhood are associated with an increased risk of developing depression and psychosis in young adulthood. Inflammatory pathways may provide important new intervention and prevention targets for these disorders. Inflammation might explain the high comorbidity between heart disease, diabetes mellitus, depression, and schizophrenia.

Background: An argument often used to support the view that psychotic experiences (PEs) in general population samples are a valid phenotype for studying the aetiology of schizophrenia is that risk factors for schizophrenia show similar patterns of association with PEs. However, PEs often co-occur with depression, and no study has explicitly tested whether risk factors for schizophrenia are shared between PEs and depression, or are psychopathology specific, while jointly modelling both outcomes., Method: We used data from 7030 subjects from a birth cohort study. Depression and PEs at age 18 years were assessed using self-report questionnaires and semi-structured interviews. We compared the extent to which risk factors for schizophrenia across sociodemographic, familial, neurodevelopmental, stress-adversity, emotional-behavioural and substance use domains showed different associations with PEs and depression within bivariate models that allowed for their correlation., Results: Most of the exposures examined were associated, to a similar degree, with an increased risk of both outcomes. However, whereas female sex and family history of depression showed some discrimination as potential risk factors for depression and PEs, with stronger associations in the former, markers of abnormal neurodevelopment showed stronger associations with PEs., Conclusions: The argument that PEs are valid markers for studying the aetiology of schizophrenia, made simply on the basis that they share risk factors in common, is not well supported. PEs seem to be a weak index of genetic and environmental risk for schizophrenia; however, studies disentangling aetiological pathways to PEs from those impacting upon co-morbid psychopathology might provide important insights into the aetiology of psychotic disorders.

Background: Peer victimization is ubiquitous across schools and cultures, and has been suggested as one developmental pathway to anxiety disorders. However, there is a dearth of prospective studies examining this relationship. The purpose of this cohort study was to examine the association between peer victimization during adolescence and subsequent anxiety diagnoses in adulthood. A secondary aim was to investigate whether victimization increases risk for severe anxiety presentations involving diagnostic comorbidity., Methods: The sample comprised 6,208 adolescents from the Avon Longitudinal Study of Parents and Children who were interviewed about experiences of peer victimization at age 13. Maternal report of her child's victimization was also assessed. Anxiety disorders at age 18 were assessed with the Clinical Interview Schedule-Revised. Multivariable logistic regression was used to examine the association between victimization and anxiety diagnoses adjusted for potentially confounding individual and family factors. Sensitivity analyses explored whether the association was independent of diagnostic comorbidity with depression., Results: Frequently victimized adolescents were two to three times more likely to develop an anxiety disorder than nonvictimized adolescents (OR = 2.49, 95% CI: 1.62-3.85). The association remained after adjustment for potentially confounding individual and family factors, and was not attributable to diagnostic overlap with depression. Frequently victimized adolescents were also more likely to develop multiple internalizing diagnoses in adulthood., Conclusions: Victimized adolescents are at increased risk of anxiety disorders in later life. Interventions to reduce peer victimization and provide support for victims may be an effective strategy for reducing the burden associated with these disorders., (© 2014 The Authors. Depression and Anxiety published by Wiley Periodicals, Inc.)

Introduction: The most frequent complications of AF ablation (AFA) are related to vascular access, but there is little evidence as to how these can be minimized., Methods: Consecutive patients undergoing AFA at a high-volume center received either standard care (Group S) or routine ultrasound-guided vascular access (Group U). Vascular complications were assessed before hospital discharge and by means of postal questionnaire 1 month later. Outcome measures were BARC 2+ bleeding complications, postprocedural pain, and prolonged bruising., Results: Patients in Group S (n = 146) and U (n = 163) were well matched at baseline. Follow-up questionnaires were received from 92.6%. Patients in Group U were significantly less likely to have a BARC 2+ bleed, 10.4% versus 19.9% P = 0.02, were less likely to suffer groin pain after discharge (27.1% vs. 42.8%; P = 0.006) and were less likely to experience prolonged local bruising (21.5% vs. 40.4%; P = 0.001). Multivariable logistic regression analysis revealed a significant association of vascular complications with nonultrasound guided access (OR 3.12 95%CI 1.54-5.34; P = 0.003) and increasing age (OR 1.05 95%CI 1.01-1.09; P = 0.02)., Conclusion: Routine use of ultrasound-guided vascular access for AFA is associated with a significant reduction in bleeding complications, postprocedural pain, and prolonged bruising when compared to standard care., (© 2014 Wiley Periodicals, Inc.)

Background: Victims of bullying are at risk for psychotic experiences in early adolescence. It is unclear if this elevated risk extends into late adolescence. The aim of this study was to test whether bullying perpetration and victimization in elementary school predict psychotic experiences in late adolescence., Method: The current study is based on the Avon Longitudinal Study of Parents and Children (ALSPAC), a prospective community-based study. A total of 4720 subjects with bullying perpetration and victimization were repeatedly assessed between the ages of 8 and 11 years by child and mother reports. Suspected or definite psychotic experiences were assessed with the Psychosis-Like Symptoms semi-structured interview at age 18 years., Results: Controlling for child's gender, intelligence quotient at age 8 years, childhood behavioural and emotional problems, and also depression symptoms and psychotic experiences in early adolescence, victims [child report at 10 years: odds ratio (OR) 2.4, 95% confidence interval (CI) 1.6-3.4; mother report: OR 1.6, 95% CI 1.1-2.3], bully/victims (child report at 10 years: OR 3.1, 95% CI 1.7-5.8; mother: OR 2.9, 95% CI 1.7-5.0) and bullies (child report at 10 years: OR 4.9, 95% CI 1.3-17.7; mother: OR 1.2, 95% CI 0.46-3.1, n.s.) had a higher prevalence of psychotic experiences at age 18 years. Path analysis revealed that the association between peer victimization in childhood and psychotic experiences at age 18 years was only partially mediated by psychotic or depression symptoms in early adolescence., Conclusions: Involvement in bullying, whether as victim, bully/victim or bully, may increase the risk of developing psychotic experiences in adolescence. Health professionals should ask routinely during consultations with children about their bullying of and by peers.

Background: Some studies have found an association between elevated cortisol and subsequent depression, but findings are inconsistent. The cortisol awakening response may be a more stable measure of hypothalamic-pituitary-adrenal function and potentially of stress reactivity., Aims: To investigate whether salivary cortisol, particularly the cortisol awakening response, is associated with subsequent depression in a large population cohort., Method: Young people (aged 15 years, n = 841) from the Avon Longitudinal Study of Parents and Children (ALSPAC) collected salivary cortisol at four time points for 3 school days. Logistic regression was used to calculate odds ratios for developing depression meeting ICD-10 criteria at 18 years., Results: We found no evidence for an association between salivary cortisol and subsequent depression. Odds ratios for the cortisol awakening response were 1.24 per standard deviation (95% CI 0.93-1.66, P = 0.14) before and 1.12 (95% CI 0.73-1.72, P = 0.61) after adjustment for confounding factors. There was no evidence that the other cortisol measures, including cortisol at each time point, diurnal drop and area under the curve, were associated with subsequent depression., Conclusions: Our findings do not support the hypothesis that elevated salivary cortisol increases the short-term risk of subsequent depressive illness. The results suggest that if an association does exist, it is small and unlikely to be of clinical significance.

Background: Depression is expensive to treat, but providing ineffective treatment is more expensive. Such is the case for many patients who do not respond to antidepressant medication., Aims: To assess the cost-effectiveness of cognitive-behavioural therapy (CBT) plus usual care for primary care patients with treatment-resistant depression compared with usual care alone., Method: Economic evaluation at 12 months alongside a randomised controlled trial. Cost-effectiveness assessed using a cost-consequences framework comparing cost to the health and social care provider, patients and society, with a range of outcomes. Cost-utility analysis comparing health and social care costs with quality-adjusted life-years (QALYs)., Results: The mean cost of CBT per participant was £910. The difference in QALY gain between the groups was 0.057, equivalent to 21 days a year of good health. The incremental cost-effectiveness ratio was £14 911 (representing a 74% probability of the intervention being cost-effective at the National Institute of Health and Care Excellence threshold of £20 000 per QALY). Loss of earnings and productivity costs were substantial but there was no evidence of a difference between intervention and control groups., Conclusions: The addition of CBT to usual care is cost-effective in patients who have not responded to antidepressants. Primary care physicians should therefore be encouraged to refer such individuals for CBT.

Background: Although the relationship between maternal bonding and risk of offspring depression has been demonstrated, it is unclear whether this risk exists for subsequent generations. This study examines the association between maternal reports of her own mother's parenting and later risk of depression in offspring at age 18., Method: This study is based on data from the Avon Longitudinal Study of Parents and Children. Mothers enrolled in the study, completed the Parental Bonding Instrument to provide an assessment of how they were parented by their own mothers up to the age of 16. Offspring depression was assessed at age of 18 using the Clinical Interview Schedule-Revised. The sample comprised 10,405 respondents who had completed the Parental Bonding Instrument during the antenatal period. Results were adjusted for grandmother's history of depression, maternal depression, and a range of socioeconomic variables., Results: A one standard deviation increase in mothers' perceived lack of care in their own childhood was associated with a 16% increase in the odds of offspring depression at age 18 (odds ratios = 1.16, 95% confidence intervals = [1.04, 1.30]). This effect remained following adjustment for potential confounders (odds ratios = 1.14, 95% confidence intervals = [1.02, 1.27]). There was no evidence for an association between overprotection and offspring depression., Conclusions: This study is consistent with the hypothesis that sensitive caregiving is important to future risk of depression across generations. Preventative interventions could be aimed at promoting positive parenting practices, which may help to reduce the risk of depression in subsequent generations., (© 2013 The Authors. Depression and Anxiety published by Wiley Periodicals, Inc.)

Aims: To investigate the prevalence of cannabis use and problem use in boys and girls at age 16 years, and to investigate the role of adversity in early life and of conduct disorder between the ages of 4 and 13 years as risk factors for these outcomes., Design: Birth cohort study., Setting: England., Participants: A total of 4159 (2393 girls) participants in the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort providing information on cannabis use at age 16., Measurements: Cannabis use and problem cannabis use at age 16 were assessed by postal questionnaire. Material adversity, maternal substance use, maternal mental health and child conduct disorder were all assessed by maternal report., Findings: Cannabis use was more common among girls than boys (21.4% versus 18.3%, P = 0.005). Problem cannabis use was more common in boys than girls (3.6% versus 2.8%, P = 0.007). Early-onset persistent conduct problems were associated strongly with problem cannabis use [odds ratio (OR) = 6.46, 95% confidence interval (CI) = 4.06-10.28]. Residence in subsidized housing (OR = 3.10, 95% CI = 1.95, 4.92); maternal cannabis use (OR 8.84, 95% CI 5.64-13.9) and any maternal smoking in the postnatal period (OR = 2.69, 95% CI = 1.90-3.81) all predicted problem cannabis use. Attributable risks for adolescent problem cannabis use associated with the above factors were 25, 13, 17 and 24%, respectively., Conclusions: Maternal smoking and cannabis use, early material disadvantage and early-onset persistent conduct problems are important risk factors for adolescent problem cannabis use. This may have implications for prevention., (© 2013 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)

Importance: Some small studies suggest that maternal postnatal depression is a risk factor for offspring adolescent depression. However, to our knowledge, no large cohort studies have addressed this issue. Furthermore, only 1 small study has examined the association between antenatal depression and later offspring depression. Understanding these associations is important to inform prevention., Objective: To investigate the hypothesis that there are independent associations between antenatal and postnatal depression with offspring depression and that the risk pathways are different, such that the risk is moderated by disadvantage (low maternal education) with postnatal depression but not with antenatal depression., Design, Setting, and Participants: Prospective investigation of associations between symptoms of antenatal and postnatal parental depression with offspring depression at age 18 years in a UK community-based birth cohort (Avon Longitudinal Study of Parents and Children) with data from more than 4500 parents and their adolescent offspring., Main Outcomes and Measures: Diagnosis of offspring aged 18 years with major depression using the International Classification of Diseases, 10th Revision., Results: Antenatal depression was an independent risk factor. Offspring were 1.28 times (95% CI, 1.08-1.51; P = .003) more likely to have depression at age 18 years for each standard deviation increase in maternal depression score antenatally, independent of later maternal depression. Postnatal depression was also a risk factor for mothers with low education, with offspring 1.26 times (95% CI, 1.06-1.50; P = .01) more likely to have depression for each standard deviation increase in postnatal depression score. However, for more educated mothers, there was little association (odds ratio, 1.09; 95% CI, 0.88-1.36; P = .42). Analyses found that maternal education moderated the effects of postnatal but not antenatal depression. Paternal depression antenatally was not associated with offspring depression, while postnatally, paternal depression showed a similar pattern to maternal depression., Conclusions and Relevance: The findings suggest that treating maternal depression antenatally could prevent offspring depression during adulthood and that prioritizing less advantaged mothers postnatally may be most effective.

Aims: To investigate associations between socio-economic position in early life and later alcohol use and problem use among male and female adolescents., Design: Birth cohort study., Setting: South West England., Participants: A total of 2711 girls and 2379 boys with one or more measures of alcohol use or problem use at age 15 years., Measurements: Exposure measures were highest parental social class, maternal education and household disposable income (all maternal self-report before school-age); outcome measures were heavy typical drinking, frequent drinking, regular binge drinking, alcohol-related psychosocial problems and alcohol-related behavioural problems., Findings: Alcohol use and related problems were relatively common amongst adolescent girls and boys. Boys were slightly more likely to report frequent drinking and girls were slightly more likely to drink heavily and to experience alcohol-related psychosocial problems. Higher maternal education appeared protective in relation to alcohol-related problems, particularly among boys. Higher household income was associated with greater risk of alcohol use and problem use, most apparently among girls., Conclusions: Children from higher-income households in England appear to be at greater risk of some types of adolescent alcohol problems, and these risks appear different in girls compared to boys. Childhood social advantage may not generally be associated with healthier behaviour in adolescence., (© 2012 The Authors, Addiction © 2012 Society for the Study of Addiction.)

Background: Substantial numbers of adolescents self-harm, but the majority of cases do not reach the attention of medical services, making community studies essential. The prevalence of suicidal thoughts and plans at this age, and the inter-relationships between suicidal thoughts, plans and self-harm remain largely unexplored., Method: Cross-sectional analysis of self-reported questionnaire data collected from members of the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort, England. Respondents (n = 4810) were aged 16-17 years old and have been followed up since birth., Results: Altogether 905 (18.8%) respondents had ever self-harmed. The prevalence of lifetime self-harm was higher in females (25.6%) than males (9.1%). The most commonly used method was self-cutting: this was used alone or in combination in 73.5% of episodes, compared to 10.0% who took overdoses alone or in combination with other methods. Of those who reported self-harm, 25.3% wanted to die during the most recent episode. Concurrent depression was associated with a greatly increased risk of self-harm (OR 5.43). Only 12.4% of participants sought medical help following their most recent episode of self-harm, although this figure was higher (30.1%) where self-harm was carried out with desire to die. Of the whole sample, 15.8% had ever thought of killing themselves, and 4.3% had ever made plans to kill themselves. Compared to those who had never self-harmed, those who had self-harmed but not wanted to die during the most recent episode were at increased risk of ever having had suicidal thoughts (37.6% compared to 7.8% χ2 =102.3, p < 0.001) and ever making suicidal plans (8.7% compared to 0.7%, χ2 =166.9, p < 0.001). As the frequency of self-harm increased, so did the risk of suicidal thoughts and plans., Conclusions: Self-harm and suicidal thoughts are common among 16/17 year olds. Although the majority of self-harm behaviour is not accompanied by a desire to die, all self-harm regardless of motivation is associated with increased risk of suicidal thoughts and plans, particularly when it is carried out repeatedly.

Objective: To investigate the effectiveness of facilitated physical activity as an adjunctive treatment for adults with depression presenting in primary care., Design: Pragmatic, multicentre, two arm parallel randomised controlled trial., Setting: General practices in Bristol and Exeter., Participants: 361 adults aged 18-69 who had recently consulted their general practitioner with symptoms of depression. All those randomised had a diagnosis of an episode of depression as assessed by the clinical interview schedule-revised and a Beck depression inventory score of 14 or more., Interventions: In addition to usual care, intervention participants were offered up to three face to face sessions and 10 telephone calls with a trained physical activity facilitator over eight months. The intervention was based on theory and aimed to provide individually tailored support and encouragement to engage in physical activity., Main Outcome Measures: The primary outcome was self reported symptoms of depression, assessed with the Beck depression inventory at four months post-randomisation. Secondary outcomes included use of antidepressants and physical activity at the four, eight, and 12 month follow-up points, and symptoms of depression at eight and 12 month follow-up., Results: There was no evidence that participants offered the physical activity intervention reported improvement in mood by the four month follow-up point compared with those in the usual care group; adjusted between group difference in mean Beck depression inventory score -0.54 (95% confidence interval -3.06 to 1.99; P=0.68). Similarly, there was no evidence that the intervention group reported a change in mood by the eight and 12 month follow-up points. Nor was there evidence that the intervention reduced antidepressant use compared with usual care (adjusted odds ratio 0.63, 95% confidence interval 0.19 to 2.06; P=0.44) over the duration of the trial. However, participants allocated to the intervention group reported more physical activity during the follow-up period than those allocated to the usual care group (adjusted odds ratio 2.27, 95% confidence interval 1.32 to 3.89; P=0.003)., Conclusions: The addition of a facilitated physical activity intervention to usual care did not improve depression outcome or reduce use of antidepressants compared with usual care alone., Trial Registration: Current Controlled Trials ISRCTN16900744.

Purpose: In a nationally representative population-based study in England, we estimated the burden of psychiatric and neurodevelopmental comorbidities in people with epilepsy. We investigated whether any overrepresentation of comorbidities could be explained by epilepsy being a chronic medical or neurologic condition, or by the confounding effect of demographic and socioeconomic factors or other health conditions., Methods: The Adult Psychiatric Morbidity Survey 2007 comprised detailed interviews with 7,403 individuals living in private households in England. Doctor-diagnosed epilepsy (and asthma, diabetes, and migraine, chronic conditions for comparison) was ascertained by self-report, and extensive diagnostic and screening interviews were used to assess psychiatric and neurodevelopmental conditions., Key Findings: The estimated lifetime prevalence of epilepsy in the adult (≥ 16 years old) population of England was 1.2% (95% confidence interval [CI] 1.0-1.5). Almost one-third of the people with epilepsy had an International Classification of Diseases, Tenth Revision (ICD-10) anxiety or depressive disorder (compared with one in six people without epilepsy). Among these, social phobia and agoraphobia, generalized anxiety disorder, depression, and measures of suicidality had strong associations with epilepsy, which remained robust after accounting for potential confounders. These associations were consistently stronger than those in people with asthma or diabetes, and similar to those in people reporting migraine or chronic headaches. Epilepsy was also strongly associated with autism spectrum disorders (odds ratio [OR] 7.4, 95% CI 1.5-35.5) and possible eating disorders, and these associations were not evident in people with asthma, diabetes, or migraine., Significance: Psychiatric and neurodevelopmental conditions were overrepresented in people with epilepsy. These associations were stronger than with other nonneurologic chronic conditions, and not explained by confounding. Some overlap in the psychopathology observed in epilepsy and migraine cannot rule out the presence of common pathways of psychiatric comorbidity in neurologic conditions. However, associations of epilepsy with conditions such as autism spectrum disorders point to comorbidities specific to epilepsy that may not be shared by other neurologic conditions., (Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.)

Background: Psychological distress in patients who attend their GP is thought to be under-recognised. However, it is likely that both disclosure and detection are influenced by how well the patient and doctor know each another., Aim: To examine whether patient-doctor depth of relationship is associated with identification of psychological distress., Design and Setting: Cross-sectional study in general practices in and around Bristol, England., Method: Patients (aged ≥16 years) were asked to complete a questionnaire and consent to their electronic medical records being reviewed. Study GPs independently assessed patient psychological distress. Multivariable logistic regression was used to look for associations between patient-doctor depth of relationship and GP detection of patient psychological distress (defined according to the 12-item General Health Questionnaire, GHQ-12)., Results: There were 643 eligible appointments with 31 GPs. In total, 541 (84.1%) patients returned questionnaires and 490 (76.2%) consented to their records being reviewed. Patient-doctor depth of relationship was not associated with GP detection of mild to severe patient psychological distress (adjusted odds ratio [OR] 0.94, 95% CI = 0.87 to 1.02) but, in secondary analyses, it was associated with the identification of moderate to severe distress (adjusted OR 1.13, 95% CI = 1.02 to 1.26). GPs reported more patient psychological distress in patients who reported a greater depth of relationship but this did not relate to patients' GHQ-12 scores., Conclusion: Evidence to support an association between patient-doctor depth of relationship and improved GP detection of patients with psychological distress was weak, except in those patients who GPs thought were more distressed. GPs may overestimate emotional distress in patients who report deeper patient-doctor relationships.

Background and Aim: Exposure to stressful life events during pregnancy has been suggested as a potential risk factor for offspring Autism Spectrum Disorders (ASD), but the literature is limited and inconsistent. We tested the hypothesis that maternal exposure to stressful life events would be associated with increased risks of offspring ASD, and that these risks would be highest for exposures during the prenatal period., Methods and Results: We used prospectively collected data from two large population based studies in Sweden and England. In the Swedish study of 4429 ASD cases and 43277 controls, our exposure comprised the occurrence of any severe life event before and during pregnancy and the child's early life. In the English study (maximum n = 11554, ASD n = 72), we studied the risk of offspring ASD in relation to a combined maternal exposure to multiple (up to 42) common and rare life events, as well as their perceived impact upon the mother during pregnancy and early life. In crude and adjusted regression analyses in both studies, we found no evidence of an association between prenatal life events, or their number and perceived impact and the risk of offspring ASD. Sub-group analysis of ASD with and without intellectual disability in the Swedish study yielded similar results., Conclusion: We found no evidence to support the hypotheses that exposure to stressful life events during the prenatal period is associated with an increased risk of offspring ASD.

Recent reforms in Australia, England, and the Netherlands have sought to enhance the quality and accessibility of primary care. Quality improvement strategies include postgraduate training programs for family physicians, accreditation of general practitioner (GP) practices, and efforts to modify professional behaviors—for example, through clinical guideline development. Strategies for improving access include national performance targets, greater use of practice nurses, assured after-hours care, and medical advice telephone lines. All three countries have established midlevel primary care organizations both to coordinate primary care health services and to serve other functions, such as purchasing and population health planning. Better coordination of primary health care services is also the objective driving the use of patient enrollment in a single general practice. Payment reform is also a key element of English and Australian reforms, with both countries having introduced payment-for-quality initiatives. Dutch payment reform has stressed financial incentives for better management of chronic disease.