What predicts response to sertraline for people with depression in primary care? a secondary data analysis of moderators in the PANDA trial.

PURPOSE: Antidepressants are a first-line treatment for depression, yet many patients do not respond. There is a need to understand which patients have greater treatment response but there is little research on patient characteristics that moderate the effectiveness of antidepressants. This study examined potential moderators of response to antidepressant treatment. METHODS: The PANDA trial investigated the clinical effectiveness of sertraline (n = 326) compared with placebo (n = 329) in primary care patients with depressive symptoms. We investigated 11 potential moderators of treatment effect (age, employment, suicidal ideation, marital status, financial difficulty, education, social support, family history of depression, life events, health and past antidepressant use). Using multiple linear regression, we investigated the appropriate interaction term for each of these potential moderators with treatment as allocated. RESULTS: Family history of depression was the only variable with weak evidence of effect modification (p-value for interaction = 0.048), such that those with no family history of depression may have greater benefit from antidepressant treatment. We found no evidence of effect modification (p-value for interactions≥0.29) by any of the other ten variables. CONCLUSION: Evidence for treatment moderators was extremely limited, supporting an approach of continuing discuss antidepressant treatment with all patients presenting with moderate to severe depressive symptoms.

The association between sexual orientation and psychotic like experiences during adolescence: a prospective cohort study.

PURPOSE: Psychotic like experiences (PLEs) are relatively common during adolescence and associated with a range of negative outcomes. There is evidence that sexual minorities are at increased risk of mental health problems including depression, anxiety, self-harm and suicidality. However, no study has investigated the association between sexual orientation and psychotic experiences during adolescence. We compared trajectories of PLEs in sexual minority and heterosexual adolescents from 12 to 24 years of age. METHODS: We used data from the Avon Longitudinal Study of Parents and Children (ALSPAC). Participants provided data on sexual orientation at age 16 and PLEs at ages 12, 17 and 24. We used multi-level logistic regression models to test associations between sexual orientation and PLEs, before and after adjusting for covariates. We investigated whether the association differed according to time-point and sex using interaction terms. RESULTS: We found evidence that the odds of PLEs were 2.35 times (95% Confidence Interval 1.79-3.06, p < 0.0001) higher among sexual minority compared with heterosexual adolescents, across all ages, after adjusting for covariates. There was no evidence that the association between sexual orientation and PLEs differed according to time-point (p = 0.50) or sex (p = 0.29). CONCLUSION: We found an increased risk of psychosis in sexual minorities compared with heterosexuals, which was present from around 12 years of age and persisted until age 24. Early interventions to prevent this mental health inequality could include universal interventions to promote inclusivity and acceptance of diverse sexual orientations.

The selective serotonin reuptake inhibitor sertraline alters learning from aversive reinforcements in patients with depression: evidence from a randomized controlled trial.

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) are first-line pharmacological treatments for depression and anxiety. However, little is known about how pharmacological action is related to cognitive and affective processes. Here, we examine whether specific reinforcement learning processes mediate the treatment effects of SSRIs. METHODS: The PANDA trial was a multicentre, double-blind, randomized clinical trial in UK primary care comparing the SSRI sertraline with placebo for depression and anxiety. Participants (N = 655) performed an affective Go/NoGo task three times during the trial and computational models were used to infer reinforcement learning processes. RESULTS: There was poor task performance: only 54% of the task runs were informative, with more informative task runs in the placebo than in the active group. There was no evidence for the preregistered hypothesis that Pavlovian inhibition was affected by sertraline. Exploratory analyses revealed that in the sertraline group, early increases in Pavlovian inhibition were associated with improvements in depression after 12 weeks. Furthermore, sertraline increased how fast participants learned from losses and faster learning from losses was associated with more severe generalized anxiety symptoms. CONCLUSIONS: The study findings indicate a relationship between aversive reinforcement learning mechanisms and aspects of depression, anxiety, and SSRI treatment, but these relationships did not align with the initial hypotheses. Poor task performance limits the interpretability and likely generalizability of the findings, and highlights the critical importance of developing acceptable and reliable tasks for use in clinical studies. FUNDING: This article presents research supported by NIHR Program Grants for Applied Research (RP-PG-0610-10048), the NIHR BRC, and UCL, with additional support from IMPRS COMP2PSYCH (JM, QH) and a Wellcome Trust grant (QH).

The association between academic achievement goals and adolescent depressive symptoms: a prospective cohort study in Australia.

BACKGROUND: Students define academic competence across two axes: developing skills and understanding (mastery) versus comparisons with peers (performance), and achieving goals (approach) versus avoiding failure (avoidance). We aimed to examine the longitudinal association between achievement goals and adolescent depressive symptoms. METHODS: We analysed data from the Kindergarten (recruited at age 4-5 years; born between March, 1999, and February, 2000; recruited from March, 2004 to November, 2004) and Baby (recruited at age 0-1 years; born between March, 2003, and February, 2004; recruited from March, 2004 to January, 2005) cohorts of the Longitudinal Study of Australian Children. Participants were identified through the Medicare enrolment database and sampled using a randomised selection stratified by postcode to represent the Australian population. Achievement goals were measured at age 12-13 years with the Achievement Goal Questionnaire (ranges from 1 to 7 on each of the four subscales), and depressive symptoms with the Short Mood and Feelings Questionnaire (score ranges from 0 to 26, with higher scores indicating more severe symptoms) at ages 14-15 years (both cohorts) and 16-17 years (Kindergarten cohort only). Analyses were linear multilevel and traditional regressions, with confounder adjustment, for participants with available data on the exposures, confounders, and outcome. FINDINGS: We included 3200 participants (1585 female and 1615 male) from the Kindergarten cohort and 2671 participants (1310 female and 1361 male) from the Baby cohort. A 1-point increase in mastery-approach goals was associated with decreased depressive symptom severity score (Kindergarten, -0·33 [95% CI -0·52 to -0·15]; Baby, -0·29 [-0·54 to -0·03]), while a 1-point increase in mastery-avoidance goals was associated with increased depressive symptom severity score (Kindergarten, 0·35 [95% CI 0·21 to 0·48]; Baby, 0·44 [0·25 to 0·64]). A 1-point increase in performance-avoidance goals was associated with increased depressive symptom severity score in the Kindergarten cohort but not the Baby cohort (Kindergarten, 0·26 [95% CI 0·11 to 0·41]; Baby, -0·04 [-0·27 to 0·19]). We found little evidence of an association between depressive symptom severity and performance-approach goals. INTERPRETATION: Depressive symptoms in adolescents were associated with their achievement goals, which could be targetable risk factors for future trials to investigate whether school-based interventions that aim to enhance factors consistent with mastery goals (ie, learning skills and understanding the subject, rather than assessing competence in comparison to peers) could prevent depression in adolescents. FUNDING: Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society.

The role of loneliness in the association between sexual orientation and depressive symptoms among older adults: A prospective cohort 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.

The role of depression and use of alcohol and other drugs after partner suicide in the association between suicide bereavement and suicide: cohort study in the Danish population.

BACKGROUND: Although suicide bereavement is associated with suicide and self-harm, evidence regarding mechanisms is lacking. We investigated whether depression and substance use (alcohol and/or other drugs) explain the association between partner suicide bereavement and suicide. METHODS: Linkage of nationwide, longitudinal data from Denmark for the period 1980-2016 facilitated a comparison of 22 668 individuals exposed to bereavement by a partner's suicide with 913 402 individuals bereaved by a partner's death due to other causes. Using causal mediation models, we estimated the degree to which depression and substance use (considered separately) mediated the association between suicide bereavement and suicide. RESULTS: Suicide-bereaved partners were found to have a higher risk of suicide (HRadj = 1.59, 95% CI 1.36-1.86) and of depression (ORadj 1.16, 95% CI 1.09-1.25) when compared to other-bereaved partners, but a lower risk of substance use (ORadj 0.83; 95% CI 0.78-0.88). An increased risk of suicide was found among any bereaved individuals with a depression diagnosis recorded post-bereavement (ORadj 3.92, 95% CI 3.55-4.34). Mediation analysis revealed that depression mediated 2% (1.68%; 95% CI 0.23%-3.14%; p = 0.024) of the association between suicide bereavement and suicide in partners when using bereaved controls. CONCLUSIONS: Depression is a partial mediator of the association between suicide bereavement and suicide. Efforts to prevent and optimize the treatment of depression in suicide-bereaved people could reduce their suicide risk. Our findings might be conservative because we did not include cases of depression diagnosed in primary care. Further work is needed to understand this and other mediators.

How do schools influence the emotional and behavioural health of their pupils? A multi-level analysis of 135 schools in the Born in Bradford inner city multi-ethnic birth cohort.

PURPOSE: To estimate variation in emotional and behavioural problems between primary schools in Bradford, an ethnically diverse and relatively deprived city in the UK. METHODS: We did a cross-sectional analysis of data collected from 2017 to 2021 as part of the 'Born In Bradford' birth cohort study. We used multilevel linear regression in which the dependent variable was the Strengths and Difficulties Questionnaire (SDQ) total score, with a random intercept for schools. We adjusted for pupil-level characteristics including age, ethnicity, socioeconomic status, and parental mental health. RESULTS: The study included 5,036 participants from 135 schools. Participants were aged 7-11 years and 56% were of Pakistani heritage. The mean SDQ score was 8.84 out of a maximum 40. We estimated that the standard deviation in school-level scores was 1.41 (95% CI 1.11-1.74) and 5.49% (95% CI 3.19-9.37%) of variation was explained at school level. After adjusting for pupil characteristics, the standard deviation of school-level scores was 1.04 (95% CI 0.76-1.32) and 3.51% (95% CI 1.75-6.18%) of variation was explained at school level. Simulation suggested that a primary school with 396 pupils at the middle of the distribution has 63 pupils (95% CI 49-78) with a 'raised' SDQ score of 15 + /40; and shifting a school from the lower to the upper quartile would prevent 26 cases (95% CI 5-46). CONCLUSION: The prevalence of emotional and behavioural problems varies between schools. This is partially explained by pupil characteristics; though residual variation in adjusted scores may suggest that schools have a differential impact on mental wellbeing.

Food Insecurity, Adolescent Suicidal Thoughts and Behaviors, and Country-Level Context: A Multi-Country Cross-Sectional Analysis.

PURPOSE: Preventing adolescent suicide is a global priority. Inequalities in adolescent suicide and attempt rates are reported across countries, including a greater risk in adolescents experiencing food insecurity. Little is known about the extent to which country-level contextual factors moderate the magnitude of socio-economic inequalities in suicidal thoughts and behavior. We aimed to examine the cross-country variability and national moderators of the association between food insecurity and suicidal thoughts and behavior in school-attending adolescents. METHODS: We analysed data on 309,340 school-attending adolescents from 83 countries that participated in the Global School-based Student Health Survey between 2003 and 2018. We used Poisson regression to identify whether suicidal thoughts and behavior were more prevalent in adolescents experiencing food insecurity compared to food-secure adolescents. Meta-regression and mixed-effects regression were used to determine whether country-level indicators moderated the magnitude of inequality. RESULTS: Suicidal ideation, suicide planning, and suicide attempts were more prevalent in food-insecure adolescents compared to food-secure adolescents in 72%, 78%, and 90% of countries respectively; however, the magnitude of these associations varied between countries. We observed wider inequalities in countries with greater levels of national wealth and universal health coverage and lower prevalence of adolescent food insecurity. Economic inequality had no moderating role. DISCUSSION: Food insecurity could contribute to the development of adolescent suicidal thoughts and behavior, and this association is likely to be moderated by country-level context. Food insecurity may be a modifiable target to help prevent adolescent suicide, especially in countries where food insecurity is less common.

Changes in Early Childhood Irritability and Its Association With Depressive Symptoms and Self-Harm During Adolescence in a Nationally Representative United Kingdom Birth Cohort.

OBJECTIVE: This study aimed to investigate longitudinal associations between changes in early childhood irritability, and depressive symptoms and self-harm at 14 years. METHOD: We used data from 7,225 children in a UK-based general population birth cohort. Childhood irritability was measured at 3, 5, and 7 years using 4 items from 2 questionnaires (the Children's Social Behaviour Questionnaire [CSBQ] and the Strengths and Difficulties Questionnaire [SDQ]). Participants reported depressive symptoms via the short Mood and Feelings Questionnaire (sMFQ) and self-harm via a single-item question, at 14 years. We used multilevel models to calculate within-child change in irritability between 3 and 7 years and examined associations between irritability, and depressive symptoms and self-harm at 14 years using linear and logistic regression models, respectively. We adjusted for child and family sociodemographic/economic characteristics, mental health difficulties, and child cognitive development. RESULTS: Irritability at ages 5 and 7 years was positively associated with depressive symptoms and self-harm at age 14 years. Irritability that remained high between 3 and 7 years was associated with depressive symptoms and self-harm at 14 years in unadjusted (depressive symptoms: ß coefficient = 0.22, 95 % CI = 0.08-0.37, p = .003; self-harm: odds ratio = 1.09, 95 % CI = 1.01-1.16, p = .019) and adjusted models (depressive symptoms: ß coefficient = 0.31, 95 % CI = 0.17-0.45, p < .001; self-harm: odds ratio = 1.12, 95 % CI = 1.0.4-1.19, p = .004). Results were similar in imputed samples. CONCLUSION: Children with irritability that remains high between 3 and 7 years are more likely to report higher depressive symptoms and self-harm during adolescence. These findings support early intervention for children with high irritability and universal interventions in managing irritability for parents of preschool-aged children.

Clinical factors associated with relapse in depression in a sample of UK primary care patients who have been on long-term antidepressant treatment.

BACKGROUND: This paper investigates whether age of onset of depression, duration of the last episode, number of episodes, and residual symptoms of depression and anxiety are associated with depression relapse in primary care patients who have been on long-term maintenance antidepressant treatment and no longer meet ICD10 criteria for depression. METHODS: An observational cohort using data from ANTLER (N = 478), a double-blind placebo-controlled trial. The primary outcome was time to relapse using the retrospective CIS-R. Participants were followed for 12 months. RESULTS: Primary outcome was available for 468 participants. Time to relapse in those with more than five previous episodes of depression was shorter, hazard ratio (HR) 1.84 (95% confidence interval [CI] 1.23-2.75) compared to people with two episodes; HR 1.57 (95% CI 1.01-2.43) after adjustment. The residual symptoms of depression at baseline were also associated with increased relapse: HR 1.05 (95% CI 1.01-1.09) and HR 1.06 (95% CI 1.01-1.12) in the adjusted model. There was evidence of reduced rate of relapse in older age of onset group: HR 0.86 (95% CI 0.78-0.95); HR attenuated after adjustment HR 0.91 (95% CI 0.81-1.02). There was no evidence of an association between duration of the current episode and residual anxiety symptoms with relapse. CONCLUSIONS: The number of previous episodes and residual symptoms of depression were associated with increased likelihood of relapse. These factors could inform joint decision making when patients are considering tapering off maintenance antidepressant treatment or considering other treatments to prevent relapse.

Longitudinal pathways between childhood BMI, body dissatisfaction, and adolescent depression: an observational study using the UK Millenium Cohort Study.

BACKGROUND: Globally, more adolescents are having depressive symptoms than in the past. High BMI is a risk factor for depressive symptoms, potentially acting via increased body dissatisfaction. Robust longitudinal evidence of these associations could help to inform preventive interventions, but such evidence remains scarce. We investigated the longitudinal associations between BMI at age 7 years and depressive symptoms at age 14 years (objective 1), BMI at age 7 years and body dissatisfaction at age 11 years (objective 2), and body dissatisfaction at age 11 years and depression at age 14 years (objective 3). We also investigated the extent to which body dissatisfaction mediated the association between BMI and depressive symptoms (objective 4). METHODS: This study used data from the Millennium Cohort Study, a representative longitudinal general population cohort of UK children born between Sept 1, 2000, and Jan 11, 2002. We used univariable and multivariable linear regression models to investigate the associations in objectives 1-3 adjusting for a range of child-level and family-level confounders. For mediation analyses we used non-parametric g-formula (objective 4). We reported stratified results in presence of sex differences. All analyses were based on participants with complete BMI data and imputed confounders and outcomes. FINDINGS: Our sample included 13 135 participants. Of these, 6624 (50·4%) were male participants and 6511 (49·6%) were female participants; 11 096 (84·4%) were of White ethnicity and 2039 (15·6%) were from a minority ethnic background. At baseline, mean age was 7·2 years (SD 0·25, range 6·3-8·3). In multivariable models, an SD increase in BMI at age 7 years was associated with greater depressive symptoms at age 14 years (estimated regression coefficient [coeff]: 0·30, 95% CI 0·17-0·43) and greater body dissatisfaction at age 11 years (coeff 0·15, 0·12-0·18). Greater body dissatisfaction at age 11 years was associated with higher depressive symptoms at age 14 years (coeff 0·60, 0·52-0·68). All these associations were twice as large in girls as in boys. Body dissatisfaction explained 43% of the association between BMI and depression in girls. INTERPRETATION: Our findings bear relevance for interventions aimed at reducing weight in childhood and reducing body dissatisfaction. Implementation of evidence-based body image interventions and identification of drivers of weight stigma should be key public health priorities. Interventions aiming to reduce weight in childhood need to avoid increasing body dissatisfaction and should target environmental drivers of weight rather than individuals. FUNDING: Wellcome Trust; The Royal Society; Economic and Social Research Council; and the National Institute for Health and Care Research.

South Asian, Black and White ethnicity and the effect of potentially modifiable risk factors for dementia: A study in English electronic health records.

INTRODUCTION: We aimed to investigate ethnic differences in the associations of potentially modifiable risk factors with dementia. METHODS: We used anonymised data from English electronic primary care records for adults aged 65 and older between 1997 and 2018. We used Cox regression to investigate main effects for each risk factor and interaction effects between each risk factor and ethnicity. RESULTS: We included 865,674 people with 8,479,973 person years of follow up. Hypertension, dyslipidaemia, obesity and diabetes were more common in people from minority ethnic groups than White people. The impact of hypertension, obesity, diabetes, low HDL and sleep disorders on dementia risk was increased in South Asian people compared to White people. The impact of hypertension was greater in Black compared to White people. DISCUSSION: Dementia prevention efforts should be targeted towards people from minority ethnic groups and tailored to risk factors of particular importance.

The association between higher education attendance and common mental health problems among young people in England: evidence from two population-based cohorts.

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.

Investigating risk of self-harm and suicide on anniversaries after bereavement by suicide and other causes: a Danish population-based self-controlled case series study.

AIMS: To investigate mechanisms of suicide risk in people bereaved by suicide, prompted by observations that bereaved people experience higher levels of distress around dates of emotional significance. We hypothesised that suicide-bereaved first-degree relatives and partners experience an increased risk of self-harm and suicide around dates of (i) anniversaries of the death and (ii) the deceased's birthday, compared with intervening periods. METHODS: We conducted a self-controlled case series study using national register data on all individuals living in Denmark from 1 January 1980 to 31 December 2016 and who were bereaved by the suicide of a first-degree relative or partner (spouse or cohabitee) during that period, and who had the outcome (any episode of self-harm or suicide) within 5 years and 6 weeks of the bereavement. We compared relative incidence of suicidal behaviour in (i) the first 30 days after bereavement and (ii) in the aggregated exposed periods (6 weeks either side of death anniversaries; 6 weeks either side of the deceased's birthdays) to the reference (aggregated unexposed intervening periods). As an indirect comparison, we repeated these models in people bereaved by other causes. RESULTS: We found no evidence of an elevated risk of suicidal behaviour during periods around anniversaries of a death or the deceased's birthdays in people bereaved by suicide (adjusted incidence rate ratio [IRRadj] = 1.00; 95% confidence interval [CI] = 0.87-1.16) or other causes (IRRadj = 1.04; 95% CI = 1.00-1.08) compared with intervening periods. Rates were elevated in the 30 days immediately after bereavement by other causes (IRRadj: 1.95, 95% CI: 1.77-2.22). CONCLUSIONS: Although people bereaved by suicide are at elevated risk of self-harm and suicide, our findings do not suggest that this risk is heightened around emotionally significant anniversaries. Bereavement care should be accessible at all points after a traumatic loss as needs will differ over the grief trajectory.

The association between academic pressure and adolescent mental health problems: A systematic review.

BACKGROUND: Academic pressure is a potential contributor to adolescent mental health problems, but international evidence on this association has never been synthesised. METHODS: We conducted the first systematic review of the association between academic pressure and adolescent depression, anxiety, self-harm, suicidality, suicide attempts and suicide. We searched MEDLINE, PsycINFO, ERIC and Web of Science (core collection) up to November 24, 2022, for studies of school-going children or adolescents, which measured academic pressure or timing within the school year as the exposure and depression, anxiety, self-harm, or suicidal ideation, attempts or suicide as outcomes. Risk of bias was assessed using the Mixed Methods Appraisal Tool. We used narrative synthesis to summarise the evidence. The review was prospectively registered with PROSPERO (CRD42021232702). RESULTS: We included 52 studies. Most studies assessed mixed anxiety and depressive symptoms (n = 20) or depressive symptoms (n = 19). Forty-eight studies found evidence of a positive association between academic pressure or timing within the school year and at least one mental health outcome. LIMITATIONS: Most studies were cross-sectional (n = 39), adjusted for a narrow range of confounders or had other limitations which limited the strength of causal inferences. CONCLUSIONS: We found evidence that academic pressure is a potential candidate for public health interventions which could prevent adolescent mental health problems. Large population-based cohort studies are needed to investigate whether academic pressure is a causal risk factor that should be targeted in school- and policy-based interventions. FUNDING: UCL Health of the Public; Wellcome Institutional Strategic Support Fund.

The association of alcohol dependence and consumption during adolescence with depression in young adulthood, in England: a prospective cohort study.

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).

Reliability of the retrospective Clinical Interview Schedule Revised (rCIS-R) to assess relapse in depression in primary care patients.

OBJECTIVES: We are not aware of a simple and short structured measure that retrospectively assesses time to relapse for depression. We developed the retrospective Clinical Interview Schedule Revised (rCIS-R) to assess depression relapse in the previous 12 weeks, for use in a clinical trial of maintenance antidepressant treatment. We assessed test-retest reliability and construct validity in relation to a Global Rating Question (GRQ) about worsening mood, participants stopping their study medication and Patient Health Questionnaire (PHQ-9) scores. METHODS: In our study 444 participants provided data for rCIS-R, GRQ and PHQ-9 and 396 participants completed rCIS-R on two occasions about 30 minutes apart. The reliability study was nested within a randomised controlled trial (ANTLER). RESULTS: We found substantial test-retest agreement for the rCIS-R definition of relapse (kappa 0.84 (95%CI 0.71 to 0.97)), for individual sections and timing of relapse (Intraclass Correlation Coefficient 0.94 (95%CI 0.92 to 0.95)). Comparison of relapse with GRQ, stopping study medication and PHQ-9 supported the construct validity of the rCIS-R. CONCLUSIONS: The rCIS-R provides a reliable way of assessing relapse of depression over the previous 12 weeks. Its brevity, self-report format, simplicity of scoring and absence of training requirement makes it attractive to use in randomised controlled trials.

A rapid realist review of universal interventions to promote inclusivity and acceptance of diverse sexual and gender identities in schools.

Universal interventions to promote inclusivity and acceptance of diverse sexual and gender identities in schools could help to prevent mental health problems in this population. We reviewed evidence and developed programme theories to explain which universal interventions work, for whom, in which contexts and why. We conducted a rapid realist review and extracted data in context-mechanism-outcome configurations, to develop and refine programme theories. We included 53 sources and identified five intervention themes: student pride clubs, inclusive antibullying and harassment policies, inclusive curricula, workshops and staff training. Here, we show that these interventions could work by reducing discrimination, bullying and marginalization. Interventions appear to work best when school staff are trained and the school climate is supportive and may be less effective for boys, gender minority students and bisexual students. Our findings provide guiding principles for schools to develop interventions and should encourage primary research to confirm, refute or refine our programme theories.