Antidepressants’ effects are established in randomised controlled trials (RCTs), but not in the real world.

To investigate real-world comparative effects of antidepressants for depression and compare them with RCTs.

We performed a cohort study based on the QResearch database. We included people with a newly recorded diagnosis of depression, exposed to licensed antidepressants in the UK. We assessed all-cause dropouts (acceptability), dropouts for adverse events (tolerability), occurrence of at least one adverse event (safety), and response and remission on the Patient Health Questionnaire (PHQ)-9 (effectiveness) at 2 and 12 months. Logistic regressions were used to compute adjusted-odds ratio (aOR) with 99% CIs, assessing the associations between exposure to each antidepressant against fluoxetine (comparator) and outcomes of interest. We compared estimates from the real world with RCTs using ratio-of-odds ratio (ROR) with 95% CI.

A total of 673 177 depressed people were studied: females 57.1%, mean age 42.8 (s.d. 17.7) years, mean baseline PHQ-9 17.1 (s.d. 5.0) (moderately severe depression). At 2 months, antidepressant acceptability was 61.4%, tolerability 94.4%, safety 54.5%, PHQ-9 decreased to 12.3 (s.d. 6.5). At 12 months, acceptability was 12.3%, tolerability 87.5%, safety 28.8%, PHQ-9 12.9 (s.d. 6.8). In the short and long term, tricyclics, mirtazapine and trazodone were worse than fluoxetine for most outcomes; citalopram had better acceptability than fluoxetine (aOR 0.95; 99% CI 0.92, 0.97), sertraline had lower tolerability (aOR 1.12; 99% CI 1.06, 1.18), and both citalopram and sertraline had lower safety (aOR 1.17 and 1.25, respectively). In the long term, citalopram had better acceptability (aOR 0.78; 99% CI 0.76, 0.81) and effectiveness (aOR 1.12 for both response and remission), but worse tolerability (aOR 1.09; 99% CI 1.06, 1.13) and safety (aOR 1.12; 99% CI 1.08, 1.16). Observational and randomised data were similar for citalopram and sertraline, while there was some difference for drugs less prescribed in the real world.

Antidepressants showed low acceptability, moderate-to-high tolerability and safety, and small-to-moderate effectiveness in the real world. Real-world and RCT estimates showed similar findings only when the analyses were carried out using large datasets; otherwise, the results diverged.

Discipline is a crucial aspect of parenting, shaping child development and behaviour. Time-out, a widely used disciplinary strategy with a strong evidence-base, has recently come under scrutiny with concerns about potential adverse effects on children's emotional development and attachment, particularly for those with a history of adversity.

To contribute critical empirical insights to the current controversy surrounding time-out by exploring the associations among time-out implementation, parent–child attachment and child mental health, and whether adversity exposure moderated these associations.

This cross-sectional study utilised a nationally representative sample of 474 primary caregivers in Australia, with children aged 6–8 years, who completed an online survey. Measures included the Implementation of Time-out Scale, Adverse Life Experiences Scale, Primary Attachment Style Questionnaire, Strengths and Difficulties Questionnaire and Spence Child Anxiety Scale.

Appropriately implemented time-out was associated with enhanced mental health and attachment, while inappropriate time-out correlated with adverse child outcomes. Exposure to adversity moderated the relationship between time-out implementation and child well-being, such that children exposed to adversity were most likely to experience attachment enhancement from appropriately implemented time-out.

Despite recent concerns of harm caused by time-out, particularly for children with a history of adversity, findings support the beneficial impact of time-out on child well-being and attachment when implemented in accordance with evidence-based parameters. Combatting misinformation and disseminating evidence-based time-out guidelines is crucial for promoting child well-being and attachment, especially for children who have experienced adversity.

The clinical high risk for psychosis (CHR-p) syndrome enables early identification of individuals at risk of schizophrenia and related disorders. We differentiate between the stigma associated with the at-risk identification itself (‘labelling-related’ stigma) versus stigma attributed to experiencing mental health symptoms (‘symptom-related’ stigma) and examine their relationships with key psychosocial variables.

We compare labelling- and symptom-related stigma in rates of endorsement and associations with self-esteem, social support loss and quality of life.

We assessed stigma domains of shame-related emotions, secrecy and experienced discrimination for both types of stigma. Individuals at CHR-p were recruited across three sites (N = 150); primary analyses included those who endorsed awareness of psychosis risk (n = 113). Paired-sample t-tests examined differences in labelling- versus symptom-related stigma; regressions examined associations with psychosocial variables, controlling for covariates, including CHR-p symptoms.

Respondents reported greater symptom-related shame, but more labelling-related secrecy. Of the nine significant associations between stigma and psychosocial variables, eight were attributable to symptom-related stigma, even after adjusting for CHR-p symptoms.

Stigma attributed to symptoms had a stronger negative association with psychosocial variables than did labelling-related stigma among individuals recently identified as CHR-p. That secrecy related to the CHR-p designation was greater than its symptom-related counterpart suggests that labelling-related stigma may still be problematic for some CHR-p participants. To optimise this pivotal early intervention effort, interventions should address the holistic ‘stigmatising experience’ of having symptoms, namely any harmful reactions received as well as participants’ socially influenced concerns about what their experiences mean, in addition to the symptoms themselves.

Abrupt cessation of heavy cannabis use can cause a withdrawal syndrome characterised by irritability, anxiety, insomnia, reduced appetite and restlessness. Recent reports have also described people in whom cannabis withdrawal immediately preceded the acute onset of psychosis.

To identify cases of psychosis associated with cannabis withdrawal.

We completed a systematic review of the literature, which comprised case reports, case series and other studies. We also searched a large electronic database of psychiatric healthcare records.

The systematic review identified 44 individuals from 21 studies in whom cannabis withdrawal preceded the development of acute psychosis. In the health record study, we identified another 68 people, of whom 47 involved a first episode of psychosis and 21 represented further episodes of an existing psychotic disorder. Almost all people were daily cannabis users who had stopped using cannabis abruptly. Individuals who continued to use cannabis after the acute psychotic episode had a much higher risk of subsequent relapse than those who abstained (odds ratio 13.9 [95% CI: 4.1 to 56.9]; χ2 = 20.1, P < 0.00001).

Abrupt cannabis withdrawal may act as a trigger for the first episode of psychosis and a relapse of an existing psychosis. Acute psychotic symptoms can emerge after the cessation, as well as following the use, of cannabis.

In patients with treatment resistant depression (TRD), the ESCAPE-TRD study showed esketamine nasal spray was superior to quetiapine extended release.

To determine the robustness of the ESCAPE-TRD results and confirm the superiority of esketamine nasal spray over quetiapine extended release.

ESCAPE-TRD was a randomised, open-label, rater-blinded, active-controlled phase IIIb trial. Patients had TRD (i.e. non-response to two or more antidepressive treatments within a major depressive episode). Patients were randomised 1:1 to flexibly dosed esketamine nasal spray or quetiapine extended release, while continuing an ongoing selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor. The primary end-point was achieving a Montgomery–Åsberg Depression Rating Scale score of ≤10 at Week 8, while the key secondary end-point was remaining relapse free through Week 32 after achieving remission at Week 8. Sensitivity analyses were performed on these end-points by varying the definition of remission based on timepoint, threshold and scale.

Of 676 patients, 336 were randomised to esketamine nasal spray and 340 to quetiapine extended release. All sensitivity analyses on the primary and key secondary end-point favoured esketamine nasal spray over quetiapine extended release, with relative risks ranging from 1.462 to 1.737 and from 1.417 to 1.838, respectively (all p < 0.05). Treatment with esketamine nasal spray shortened time to first and confirmed remission (hazard ratio: 1.711 [95% confidence interval 1.402, 2.087], p < 0.001; 1.658 [1.337, 2.055], p < 0.001).

Esketamine nasal spray consistently demonstrated significant superiority over quetiapine extended release using all pre-specified definitions for remission and relapse. Sensitivity analyses supported the conclusions of the primary ESCAPE-TRD analysis and demonstrated robustness of the results.

Early intervention in psychosis (EIP) services improve outcomes for young people, but approximately 30% disengage.

To test whether a new motivational engagement intervention would prolong engagement and whether it was cost-effective.

We conducted a multicentre, single-blind, parallel-group, cluster randomised controlled trial involving 20 EIP teams at five UK National Health Service (NHS) sites. Teams were randomised using permuted blocks stratified by NHS trust. Participants were all young people (aged 14–35 years) presenting with a first episode of psychosis between May 2019 and July 2020 (N = 1027). We compared the novel Early Youth Engagement (EYE-2) intervention plus standardised EIP (sEIP) with sEIP alone. The primary outcome was time to disengagement over 12–26 months. Economic outcomes were mental health costs, societal costs and socio-occupational outcomes over 12 months. Assessors were masked to treatment allocation for primary disengagement and cost-effectiveness outcomes. Analysis followed intention-to-treat principles. The trial was registered at ISRCTN51629746.

Disengagement was low at 15.9% overall in standardised stand-alone services. The adjusted hazard ratio for EYE-2 + sEIP (n = 652) versus sEIP alone (n = 375) was 1.07 (95% CI 0.76–1.49; P = 0.713). The health economic evaluation indicated lower mental healthcare costs linked to reductions in unplanned mental healthcare with no compromise of clinical outcomes, as well as some evidence for lower societal costs and more days in education, training, employment and stable accommodation in the EYE-2 group.

We found no evidence that EYE-2 increased time to disengagement, but there was some evidence for its cost-effectiveness. This is the largest study to date reporting positive engagement, health and cost outcomes in a total EIP population sample. Limitations included high loss to follow-up for secondary outcomes and low completion of societal and socio-occupational data. COVID-19 affected fidelity and implementation. Future engagement research should target engagement to those in greatest need, including in-patients and those with socio-occupational goals.

Social prescribing is growing rapidly globally as a way to tackle social determinants of health. However, whom it is reaching and how effectively it is being implemented remains unclear.

To gain a comprehensive picture of social prescribing in the UK, from referral routes, reasons, to contacts with link workers and prescribed interventions.

This study undertook the first analyses of a large database of administrative data from over 160 000 individuals referred to social prescribing across the UK. Data were analysed using descriptive analyses and regression modelling, including logistic regression for binary outcomes and negative binomial regression for count variables.

Mental health was the most common referral reason and mental health interventions were the most common interventions prescribed. Between 72% and 85% of social prescribing referrals were from medical routes (primary or secondary healthcare). Although these referrals demonstrated equality in reaching across sociodemographic groups, individuals from more deprived areas, younger adults, men, and ethnic minority groups were reached more equitably via non-medical routes (e.g. self-referral, school, charity). Despite 90% of referrals leading to contact with a link worker, only 38% resulted in any intervention being received. A shortage of provision of community activities – especially ones relevant to mental health, practical support and social relationships – was evident. There was also substantial heterogeneity in how social prescribing is implemented across UK nations.

Mental health is the leading reason for social prescribing referrals, demonstrating its relevance to psychiatrists. But there are inequalities in referrals. Non-medical referral routes could play an important role in addressing inequality in accessing social prescribing and therefore should be prioritised. Additionally, more financial and infrastructural resource and strategic planning are needed to address low intervention rates. Further investment into large-scale data platforms and staff training are needed to continue monitoring the development and distribution of social prescribing.

Minoritised young people face a double burden of discrimination through increased risk of stress and differential treatment access. However, acute care pathways for minoritised young people with urgent mental health needs are poorly understood.

To explore variation in stress-related presentations (SRPs) to acute hospitals across racial-ethnic groups in England.

We examined rates, distribution, duration and types of SRPs across racial-ethnic groups in a retrospective cohort of 11- to 15-year-olds with one or more emergency hospital admissions between April 2014 and March 2020. SRPs were defined as emergency admissions for potentially psychosomatic symptoms, self-harm and internalising, externalising and thought disorders.

White British (8–38 per 1000 births) and Mixed White–Black (9–42 per 1000 births) young people had highest rates of SRPs, whereas Black African (5–14 per 1000 births), Indian (6–19 per 1000 births) and White other (4–19 per 1000 births) young people had the lowest rates of SRPs. The proportion of readmissions were highest for Pakistani (47.7%), White British (41.4%) and Mixed White–Black (41.3%) groups. Black Other (36.4%) and White Other (35.8%) groups had the lowest proportions of readmissions. The proportion of admission durations ≥3 days was higher for Black Other (16.6%), Bangladeshi (16.3%), Asian Other (15.9%) and Black Caribbean (15.8%) groups than their White British (11.9%) and Indian (11.8%) peers. The type of SRPs varied across racial-ethnic groups.

Patterns of SRP admissions systematically differed across racial-ethnic groups, indicative of inequitable triage, assessment and treatment processes. These findings highlight the need for implementation of race equality frameworks to address structural racism in healthcare pathways.

An important contributor to the decreased life expectancy of individuals with schizophrenia is sudden cardiac death. Arrhythmic disorders may play an important role herein, but the nature of the relationship between schizophrenia and arrhythmia is unclear.

To assess shared genetic liability and potential causal effects between schizophrenia and arrhythmic disorders and electrocardiogram (ECG) traits.

We leveraged summary-level data of large-scale genome-wide association studies of schizophrenia (53 386 cases, 77 258 controls), arrhythmic disorders (atrial fibrillation, 55 114 cases, 482 295 controls; Brugada syndrome, 2820 cases, 10 001 controls) and ECG traits (heart rate (variability), PR interval, QT interval, JT interval and QRS duration, n = 46 952–293 051). We examined shared genetic liability by assessing global and local genetic correlations and conducting functional annotation. Bidirectional causal relations between schizophrenia and arrhythmic disorders and ECG traits were explored using Mendelian randomisation.

There was no evidence for global genetic correlation, except between schizophrenia and Brugada syndrome (rg = 0.14, 95% CIs = 0.06–0.22, P = 4.0E−04). In contrast, strong positive and negative local correlations between schizophrenia and all cardiac traits were found across the genome. In the most strongly associated regions, genes related to immune and viral response mechanisms were overrepresented. Mendelian randomisation indicated that liability to schizophrenia causally increases Brugada syndrome risk (beta = 0.14, CIs = 0.03–0.25, P = 0.009) and heart rate during activity (beta = 0.25, CIs = 0.05–0.45, P = 0.015).

Despite little evidence for global genetic correlation, specific genomic regions and biological pathways emerged that are important for both schizophrenia and arrhythmia. The putative causal effect of liability to schizophrenia on Brugada syndrome warrants increased cardiac monitoring and early medical intervention in people with schizophrenia.

Personalised management of recurrent depression, considering individual patient characteristics, is crucial.

This study evaluates the potentially different mediating role of mindfulness skills in managing recurrent depression using mindfulness-based cognitive therapy (MBCT) among people with varying depression severity.

Data from the Prevention of Depressive Relapse or Recurrence (PREVENT) trial, comparing MBCT (with antidepressant medication (ADM) tapering support, MBCT-tapering support) versus maintenance-ADM, were used. The study included pre, post, 9-, 12-, 18- and 24-month follow-ups. Adults with ≥3 previous major depressive episodes, in full/partial remission (below threshold for a current episode), on ADM, were assessed for eligibility in primary care practices in the UK. People were randomised (1:1) to MBCT-tapering support or maintenance-ADM. We used the Beck Depression Inventory-II to evaluate depressive symptom changes over the six time points. Pre-post treatment, we employed the Five Facets of Mindfulness Questionnaire to gauge mindfulness skills. Baseline symptom and history variables were used to identify individuals with varying severity profiles. We conducted Latent Profile Moderated-Mediation Growth Mixture Models.

A total of 424 people (mean (s.d.) age = 49.44 (12.31) years; with 325 (76.7%) self-identified as female) were included. A mediating effect of mindfulness skills, between trial arm allocation and the linear rate of depressive symptoms change over 24 months, moderated by depression severity, was observed (moderated-mediation index = −0.27, 95% CI = −0.66, −0.03). Conditional indirect effects were −0.42 (95% CI = −0.78, −0.18) for higher severity (expected mean BDI-II reduction = 10 points), and −0.15 (95% CI = −0.35, −0.02) for lower severity (expected mean BDI-II reduction = 3.5 points).

Mindfulness skills constitute a unique mechanism driving change in MBCT (versus maintenance-ADM). Individuals with higher depression severity may benefit most from MBCT-tapering support for residual symptoms. It is unclear if these effects apply to those with a current depressive episode. Future research should investigate individuals who are not on medication. This study provides preliminary evidence for personalised management of recurrent depression.

ISRCTN26666654.

Attempts to use artificial intelligence (AI) in psychiatric disorders show moderate success, highlighting the potential of incorporating information from clinical assessments to improve the models. This study focuses on using large language models (LLMs) to detect suicide risk from medical text in psychiatric care.

To extract information about suicidality status from the admission notes in electronic health records (EHRs) using privacy-sensitive, locally hosted LLMs, specifically evaluating the efficacy of Llama-2 models.

We compared the performance of several variants of the open source LLM Llama-2 in extracting suicidality status from 100 psychiatric reports against a ground truth defined by human experts, assessing accuracy, sensitivity, specificity and F1 score across different prompting strategies.

A German fine-tuned Llama-2 model showed the highest accuracy (87.5%), sensitivity (83.0%) and specificity (91.8%) in identifying suicidality, with significant improvements in sensitivity and specificity across various prompt designs.

The study demonstrates the capability of LLMs, particularly Llama-2, in accurately extracting information on suicidality from psychiatric records while preserving data privacy. This suggests their application in surveillance systems for psychiatric emergencies and improving the clinical management of suicidality by improving systematic quality control and research.

Anorexia nervosa is a psychiatric disorder characterised by undernutrition, significantly low body weight and large, although possibly transient, reductions in brain structure. Advanced brain ageing tracks accelerated age-related changes in brain morphology that have been linked to psychopathology and adverse clinical outcomes.

The aim of the current case–control study was to characterise cross-sectional and longitudinal patterns of advanced brain age in acute anorexia nervosa and during the recovery process.

Measures of grey- and white-matter-based brain age were obtained from T1-weighted magnetic resonance imaging scans of 129 acutely underweight female anorexia nervosa patients (of which 95 were assessed both at baseline and after approximately 3 months of nutritional therapy), 39 recovered patients and 167 healthy female controls, aged 12–23 years. The difference between chronological age and grey- or white-matter-based brain age was calculated to indicate brain-predicted age difference (BrainAGEGM and BrainAGEWM).

Acute anorexia nervosa patients at baseline, but not recovered patients, showed a higher BrainAGEGM of 1.79 years (95% CI [1.45, 2.13]) compared to healthy controls. However, the difference was largely reduced for BrainAGEWM. After partial weight restoration, BrainAGEGM decreased substantially (beta = −1.69; CI [−1.93, −1.46]). BrainAGEs were unrelated to symptom severity or depression, but larger weight gain predicted larger normalisation of BrainAGEGM in the longitudinal patient sample (beta = −0.65; CI [−0.75, −0.54]).

Our findings suggest that in patients with anorexia nervosa, undernutrition is an important predictor of advanced grey-matter-based brain age, which itself might be transient in nature and largely undetectable after weight recovery.

Breast cancer is a major global health issue, especially among women. Previous research has indicated a possible association between psychiatric conditions, particularly schizophrenia, and an increased risk of breast cancer. However, the specific risk of breast cancer in women with schizophrenia, compared with those with other psychiatric disorders and the general population, remains controversial and needs further clarification.

To estimate the risk of breast cancer among people with schizophrenia compared with people with other psychiatric disorders and people in the general population.

We utilised medical claims data of women aged 18 to 80 years in the Korean National Health Information Database from 2007 to 2018. Individuals with schizophrenia were defined as women with ICD-10 codes F20 or F25 (n = 224 612). The control groups were defined as women with other psychiatric disorders (n = 224 612) and women in the general Korean population (n = 449 224). Cases and controls were matched by index date and age, in a 1:1:2 ratio. We estimated the hazard of breast cancer using the Cox proportional hazards model, adjusting for insurance premiums and medical comorbidities. Among the people with schizophrenia, we used the landmark method to estimate the association between duration of antipsychotic medication use and the incidence of breast cancer.

In multivariable Cox regression models, the hazard rate of breast cancer was 1.26 times higher in the people with schizophrenia than in the general population (95% CI: 1.20–1.32). In comparison with the psychiatric patient group, the hazard ratio was 1.17 (95% CI: 1.11–1.28). Among women with schizophrenia, the hazard of breast cancer was greater among those who took antipsychotic medications for 1 year or more compared with those who took antipsychotics for less than 6 months.

Women with schizophrenia have an elevated risk of breast cancer, and long-term use of antipsychotics is associated with an increased risk of breast cancer.

Positive, negative and disorganised psychotic symptom dimensions are associated with clinical and developmental variables, but differing definitions complicate interpretation. Additionally, some variables have had little investigation.

To investigate associations of psychotic symptom dimensions with clinical and developmental variables, and familial aggregation of symptom dimensions, in multiple samples employing the same definitions.

We investigated associations between lifetime symptom dimensions and clinical and developmental variables in two twin and two general psychosis samples. Dimension symptom scores and most other variables were from the Operational Criteria Checklist. We used logistic regression in generalised linear mixed models for combined sample analysis (n = 875 probands). We also investigated correlations of dimensions within monozygotic (MZ) twin pairs concordant for psychosis (n = 96 pairs).

Higher symptom scores on all three dimensions were associated with poor premorbid social adjustment, never marrying/cohabiting and earlier age at onset, and with a chronic course, most strongly for the negative dimension. The positive dimension was also associated with Black and minority ethnicity and lifetime cannabis use; the negative dimension with male gender; and the disorganised dimension with gradual onset, lower premorbid IQ and substantial within twin-pair correlation. In secondary analysis, disorganised symptoms in MZ twin probands were associated with lower premorbid IQ in their co-twins.

These results confirm associations that dimensions share in common and strengthen the evidence for distinct associations of co-occurring positive symptoms with ethnic minority status, negative symptoms with male gender and disorganised symptoms with substantial familial influences, which may overlap with influences on premorbid IQ.

Medications are commonly used to treat co-occurring psychopathology in persons with borderline personality disorder (BPD)

To systematically review and integrate the evidence of medications for treatment of co-occurring psychopathology in people with BPD, and explore the role of comorbidities.

Building on the current Cochrane review of medications in BPD, an update literature search was done in March 2024. We followed the methods of this Cochrane review, but scrutinised all identified placebo-controlled trials post hoc for reporting of non BPD-specific (‘co-occurring’) psychopathology, and explored treatment effects in subgroups of samples with and without defined co-occurring disorders. GRADE ratings were done to assess the evidence certainty.

Twenty-two trials were available for quantitative analyses. For antipsychotics, we found very-low-certainty evidence (VLCE) of an effect on depressive symptoms (standardised mean difference (SMD) −0.22, P = 0.04), and low-certainty evidence (LCE) of an effect on psychotic–dissociative symptoms (SMD −0.28, P = 0.007). There was evidence of effects of anticonvulsants on depressive (SMD −0.44, P = 0.02; LCE) and anxious symptoms (SMD −1.11, P < 0.00001; VLCE). For antidepressants, no significant findings were observed (VLCE). Exploratory subgroup analyses indicated a greater effect of antipsychotics in samples including participants with co-occurring substance use disorders on psychotic–dissociative symptoms (P = 0.001).

Our findings, based on VLCE and LCE only, do not support the use of pharmacological interventions in people with BPD to target co-occurring psychopathology. Overall, the current evidence does not support differential treatment effects in persons with versus without defined comorbidities. Medications should be used cautiously to target co-occurring psychopathology.

‘Inhalants’ have been associated with poorer mental health in adolescence, but little is known of associations with specific types of inhalants.

We aimed to investigate associations of using volatile substances, nitrous oxide and alkyl nitrates with mental health problems in adolescence.

We conducted a cross-sectional analysis using data from 13- to 14-year-old adolescents across England and Wales collected between September 2019 and March 2020. Multilevel logistic regression examined associations between lifetime use of volatile substances, nitrous oxide and alkyl nitrates with self-reported symptoms of probable depression, anxiety, conduct disorder and auditory hallucinations.

Of the 6672 adolescents in the study, 5.1% reported use of nitrous oxide, 4.9% volatile solvents and 0.1% alkyl nitrates. After accounting for multiple testing, adolescents who had used volatile solvents were significantly more likely to report probable depressive (odds ratio = 4.59, 95% CI 3.58, 5.88), anxiety (odds ratio = 3.47, 95% CI 2.72, 4.43) or conduct disorder (odds ratio = 7.52, 95% CI 5.80, 9.76) and auditory hallucinations (odds ratio = 5.35, 95% CI 4.00, 7.17) than those who had not. Nitrous oxide use was significantly associated with probable depression and conduct disorder but not anxiety disorder or auditory hallucinations. Alkyl nitrate use was rare and not associated with mental health outcomes. Adjustment for use of other inhalants, tobacco and alcohol resulted in marked attenuation but socioeconomic disadvantage had little effect.

To our knowledge, this study provides the first general population evidence that volatile solvents and nitrous oxide are associated with probable mental health disorders in adolescence. These findings require replication, ideally with prospective designs.

Understanding how childhood psychosocial adjustment (CPA) influences later life health outcomes is crucial for developing interventions to mitigate the long-term risk of cardiometabolic diseases (CMDs).

To investigate the association between CPA and incident CMDs in mid-life, and the mediating roles of educational attainment, smoking habits and depression during young adulthood.

A prospective cohort study utilised data from the 1958 National Child Development Study (NCDS; 1958–2013) and the 1970 British Cohort Study (BCS70; 1970–2018), encompassing 22 012 participants assessed for CPA in childhood, who were subsequently evaluated for educational attainment, smoking habits and depression in young adulthood, followed by assessments for CMDs in mid-life. CPA was assessed using the Bristol Social Adjustment Guides in the NCDS and the Rutter Child Behaviour Scale in the BCS70, with higher scores indicating poorer psychosocial adjustment. The primary outcomes were the mid-life incidences of hypertension, diabetes and obesity.

Compared with children in the lowest tertile for CPA scores, those in the middle tertile had an adjusted odds ratio for hypertension of 0.98 (95% CI 0.90–1.06), whereas those in the highest tertile had an odds ratio of 1.17 (95% CI 1.08–1.26). For diabetes, the corresponding odds ratios (95% CI) were 1.15 (0.98–1.35) and 1.39 (1.19–1.62). For obesity, the corresponding odds ratios (95% CI) were 1.08 (1.00–1.16) and 1.18 (1.09–1.27). These associations were partially mediated by educational attainment (2.4–13.9%) and depression during young adulthood (2.5–14.9%).

Poorer CPA is correlated with the development of hypertension, diabetes and obesity in mid-life. Interventions aimed at improving CPA may help in reducing the burden of these diseases in later life.

Understanding inequalities in outcomes between demographic groups is a necessary step in addressing them in clinical care. Inequalities in treatment uptake between demographic groups may explain disparities in outcomes in people with first-episode psychosis (FEP).

To investigate disparities between broad demographic groups in symptomatic improvement in patients with FEP and their relationship to treatment uptake.

We used data from 6813 patients from the 2021–2022 National Clinical Audit of Psychosis data-set. Data were grouped by category type to obtain mean outcomes before adjustment to see whether disparities in outcomes remained after differences in treatment uptake had been accounted for. After matching, the average effect of each demographic variable in terms of outcome change was calculated. Moderator effects on specific treatments were investigated using interaction terms in a regression model.

Observational results showed that patients aged 18–24 years were less likely to improve in outcome, unless adjusted for intervention uptake. Patients classified as Black and Black British were less likely to improve in outcome (moderation effect 0.04, 95% CI 0–0.07) after adjusting for treatment take-up and demographic factors. Regression analysis showed the general positive effect of supported employment interventions in improving outcomes (coefficient −0.13, 95% CI −0.07 to −0.18, P < 0.001), and moderator analysis suggested targeting particular groups for interventions.

Inequalities in treatment uptake and psychotic symptom outcome of FEP by social and demographic factors require monitoring over time. Our analysis provides a framework for monitoring health inequalities across national clinical audits in the UK.

Previous studies have indicated associations between maternal mental disorders and adverse birth outcomes; however, these studies mainly focus on certain types of mental disorders, rather than the whole spectrum.

We aimed to conduct a broad study examining all maternal mental disorder types and adverse neonatal outcomes which is needed to provide a more complete understanding of the associations.

We included 1 132 757 liveborn singletons born between 1997 and 2015 in Denmark. We compared children of mothers with a past (>2 years prior to conception; n = 48 646), recent (2 years prior to conception and during pregnancy; n = 15 899) or persistent (both past and recent; n = 10 905) diagnosis of any mental disorder, with children of mothers with no mental disorder diagnosis before the index delivery (n = 1 057 307). We also considered different types of mental disorders. We calculated odds ratios and 95% CIs of low birthweight, preterm birth, small for gestational age, low Apgar score, Caesarean delivery and neonatal death.

Odds ratios for children exposed to past, recent and persistent maternal mental disorders suggested an increased risk for almost all adverse neonatal outcomes. Estimates were highest for children in the ‘persistent’ group for all outcomes, with the exception of the association between persistent maternal mental disorders and neonatal death (odds ratio 0.96, 0.62–1.48).

Our study provides evidence for increased risk of multiple adverse neonatal outcomes among children of mothers with mental disorders, highlighting the need for close monitoring and support for women with mental disorders.