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.

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 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.

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.

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.

Clozapine is the most effective medication for treatment-resistant psychoses, but the balance of benefits and risks is understudied in real-world settings.

To examine the relative re-hospitalisation rates for mental health relapse and adverse events associated with clozapine and other antipsychotics in adult and child/youth cohorts.

Data were obtained from the Canadian Institute of Health Information for adults (n = 45 616) and children/youth (n = 1476) initially hospitalised for mental health conditions in British Columbia, Manitoba and Saskatchewan from 2008 to 2018. Patient demographics and hospitalisations were linked with antipsychotic prescriptions dispensed following the initial visit. Recurrent events survival analysis for relapse and adverse events were created and compared between clozapine and other antipsychotics.

In adults, clozapine was associated with a 14% lower relapse rate versus other drugs (adjusted hazard ratio: 0.86, 95% CI: 0.83–0.90) over the 10-year follow-up. In the first 21 months, the relapse rate was higher for clozapine but then reversed. Over 1000 person-months, clozapine-treated adults could be expected to have 38 relapse hospitalisations compared with 45 for other drugs. In children/youth, clozapine had a 38% lower relapse rate compared with other antipsychotic medications (adjusted hazard ratio: 0.62, 95% CI: 0.49–0.78) over the follow-up period. This equates to 29 hospitalisations for clozapine and 48 for other drugs over 1000 person-months. In adults, clozapine had a higher risk for adverse events (hazard ratio: 1.34, 95% CI: 1.18–1.54) over the entire follow-up compared with other antipsychotics. This equates to 1.77 and 1.30 hospitalisations over 1000 person-months for clozapine and other drugs, respectively.

Clozapine was associated with lower relapse overall, but this was accompanied by higher adverse events for adults. For children/youth, clozapine was associated with lower relapse all throughout and had no difference in adverse events compared with other antipsychotics.

Clozapine is the most effective antipsychotic for treatment-resistant psychosis. However, clozapine is underutilised in part because of potential agranulocytosis. Accumulating evidence indicates that below-threshold haematological readings in isolation are not diagnostic of life-threatening clozapine-induced agranulocytosis (CIA).

To examine the prevalence and timing of CIA using different diagnostic criteria and to explore demographic differences of CIA in patients registered on the UK Central Non-Rechallenge Database (CNRD).

We analysed data of all patients registered on the UK Clozaril® Patient Monitoring Service Central Non-Rechallenge Database (at least one absolute neutrophil count (ANC) < 1.5 × 109/L and/or white blood cell count < 3.0 × 109/L) between May 2000 and February 2021. We calculated prevalence rates of agranulocytosis using threshold-based and pattern-based criteria, stratified by demographic factors (gender, age and ethnicity). Differences in epidemiology based on rechallenge status and clozapine indication were explored. The proportion of patients who recorded agranulocytosis from a normal ANC was explored.

Of the 3029 patients registered on the CNRD with 283 726 blood measurements, 593 (19.6%) were determined to have threshold-based agranulocytosis and 348 (11.4%) pattern-based agranulocytosis. In the total sample (75 533), the prevalence of threshold-based agranulocytosis and pattern-based agranulocytosis was 0.8% and 0.5%, respectively. The median time to threshold-based agranulocytosis was 32 weeks (IQR 184) and 15 (IQR 170) weeks for pattern-based agranulocytosis. Among age groups, the prevalence of pattern-based agranulocytosis and threshold-based agranulocytosis was highest in the >48 age group. Prevalence rates were greatest for White (18%) and male individuals (13%), and lowest for Black individuals (0.1%). The proportion of people who were determined to have pattern-based agranulocytosis without passing through neutropenia was 70%.

Threshold-based definition of agranulocytosis may over-diagnose CIA. Monitoring schemes should take into consideration neutrophil patterns to correctly identify clinically relevant CIA. In marked contrast to previous studies, CIA occurred least in Black individuals and most in White individuals.

Childhood trauma is a major risk factor for chronic depression. It has been suggested that adults with chronic depression who have experienced childhood trauma may require long-term treatment owing to a breakdown of basic trust and related difficulties in developing a productive therapeutic relationship.

As empirical studies have been preliminary and scarce, we studied the effects of psychoanalytic therapy (PAT) versus cognitive–behavioural therapy (CBT) for chronic depression in adults with a history of childhood trauma. In this subgroup, we expected a greater symptom reduction in PAT compared with CBT.

In a large trial of long-term psychotherapies for chronic depression (LAC-Study; Clinical Trial Register ISRCTN91956346), 210 adults received open-ended CBT or PAT in an out-patient setting and were examined yearly over 5 years on the Beck Depression Inventory – II (BDI-II). Based on a linear mixed model approach, we tested participant-reported childhood trauma based on the Childhood Trauma Questionnaire (CTQ) as a predictor and moderator of treatment outcome. CTQ subscales were examined exploratively.

Depressive symptoms decreased over time (b = −4.55, s.e. = 0.90, 95% CI −6.32 to −2.81, T = −5.08; P < 0.001). A significant three-way interaction between childhood trauma, time and therapy group (b = −0.05, s.e. = 0.02, 95% CI −0.09 to −0.01, T = −2.42; P = 0.016) indicated that participants with childhood trauma profited especially well from PATs.

Our results indicate differential benefits from PAT compared with CBT among adults with chronic depression and a history of childhood trauma. The results have important implications for differential indication and policy.

Concern that self-harm and mental health conditions are increasing in university students may reflect widening access to higher education, existing population trends and/or stressors associated with this setting.

To compare population-level data on self-harm, neurodevelopmental and mental health conditions between university students and non-students with similar characteristics before and during enrolment.

This cohort study linked electronic records from the Higher Education Statistics Agency for 2012–2018 to primary and secondary healthcare records. Students were undergraduates aged 18 to 24 years at university entry. Non-students were pseudo-randomly selected based on an equivalent age distribution. Logistic regressions were used to calculate odds ratios. Poisson regressions were used to calculate incidence rate ratios (IRR).

The study included 96 760 students and 151 795 non-students. Being male, self-harm and mental health conditions recorded before university entry, and higher deprivation levels, resulted in lower odds of becoming a student and higher odds of drop-out from university. IRRs for self-harm, depression, anxiety, autism spectrum disorder (ASD), drug use and schizophrenia were lower for students. IRRs for self-harm, depression, attention-deficit hyperactivity disorder, ASD, alcohol use and schizophrenia increased more in students than in non-students over time. Older students experienced greater risk of self-harm and mental health conditions, whereas younger students were more at risk of alcohol use than non-student counterparts.

Mental health conditions in students are common and diverse. While at university, students require person-centred stepped care, integrated with local third-sector and healthcare services to address specific conditions.

Better knowledge about childhood trauma as a risk factor for psychiatric disorders in young people could help strengthen the timeliness and effectiveness of prevention and treatment efforts.

To estimate the prevalence and risk of psychiatric disorders in young people following exposure to childhood trauma, including interpersonal violence.

This prospective cohort study followed 8199 adolescents (age range 12–20 years) over 13–15 years, into young adulthood (age range 25–35 years). Data about childhood trauma exposure from adolescents participating in the Trøndelag Health Study (HUNT, 2006–2008) were linked to data about subsequent development of psychiatric disorders from the Norwegian Patient Registry (2008–2021).

One in four (24.3%) adolescents were diagnosed with a psychiatric disorder by young adulthood. Regression analyses showed consistent and significant relationships between childhood exposure to both interpersonal violence and other potentially traumatic events, and subsequent psychiatric disorders and psychiatric comorbidity. The highest estimates were observed for childhood exposure to two or more types of interpersonal violence (polyvictimisation), and development of psychotic disorders (odds ratio 3.41, 95% CI 1.93–5.72), stress and adjustment disorders (odds ratio 4.20, 95% CI 3.05–5.71), personality disorders (odds ratio 3.98, 95% CI 2.70–5.76), alcohol-related disorders (odds ratio 3.28, 95% CI 2.06–5.04) and drug-related disorders (odds ratio 4.67, 95% CI 2.87–7.33).

These findings emphasise the importance of integrating knowledge about childhood trauma as a potent risk factor for psychopathology into the planning and implementation of services for children, adolescents and young adults.

It remains unknown whether severe mental disorders contribute to fatally harmful effects of physical illness.

To investigate the risk of all-cause death and loss of life-years following the onset of a wide range of physical health conditions in people with severe mental disorders compared with matched counterparts who had only these physical health conditions, and to assess whether these associations can be fully explained by this patient group having more clinically recorded physical illness.

Using Czech national in-patient register data, we identified individuals with 28 physical health conditions recorded between 1999 and 2017, separately for each condition. In these people, we identified individuals who had severe mental disorders recorded before the physical health condition and exactly matched them with up to five counterparts who had no recorded prior severe mental disorders. We estimated the risk of all-cause death and lost life-years following each of the physical health conditions in people with pre-existing severe mental disorders compared with matched counterparts without severe mental disorders.

People with severe mental disorders had an elevated risk of all-cause death following the onset of 7 out of 9 broadly defined and 14 out of 19 specific physical health conditions. People with severe mental disorders lost additional life-years following the onset of 8 out 9 broadly defined and 13 out of 19 specific physical health conditions. The vast majority of results remained robust after considering the potentially confounding role of somatic multimorbidity and other clinical and sociodemographic factors.

A wide range of physical illnesses are more likely to result in all-cause death in people with pre-existing severe mental disorders. This premature mortality cannot be fully explained by having more clinically recorded physical illness, suggesting that physical disorders are more likely to be fatally harmful in this patient group.

The serotonin 4 receptor (5-HT4R) is a promising target for the treatment of depression. Highly selective 5-HT4R agonists, such as prucalopride, have antidepressant-like and procognitive effects in preclinical models, but their clinical effects are not yet established.

To determine whether prucalopride (a 5-HT4R agonist and licensed treatment for constipation) is associated with reduced incidence of depression in individuals with no past history of mental illness, compared with anti-constipation agents with no effect on the central nervous system.

Using anonymised routinely collected data from a large-scale USA electronic health records network, we conducted an emulated target trial comparing depression incidence over 1 year in individuals without prior diagnoses of major mental illness, who initiated treatment with prucalopride versus two alternative anti-constipation agents that act by different mechanisms (linaclotide and lubiprostone). Cohorts were matched for 121 covariates capturing sociodemographic factors, and historical and/or concurrent comorbidities and medications. The primary outcome was a first diagnosis of major depressive disorder (ICD-10 code F32) within 1 year of the index date. Robustness of the results to changes in model and population specification was tested. Secondary outcomes included a first diagnosis of six other neuropsychiatric disorders.

Treatment with prucalopride was associated with significantly lower incidence of depression in the following year compared with linaclotide (hazard ratio 0.87, 95% CI 0.76–0.99; P = 0.038; n = 8572 in each matched cohort) and lubiprostone (hazard ratio 0.79, 95% CI 0.69–0.91; P < 0.001; n = 8281). Significantly lower risks of all mood disorders and psychosis were also observed. Results were similar across robustness analyses.

These findings support preclinical data and suggest a role for 5-HT4R agonists as novel agents in the prevention of major depression. These findings should stimulate randomised controlled trials to confirm if these agents can serve as a novel class of antidepressant within a clinical setting.

Urbanisation is taking place worldwide and rates of mental illness are rising. There has been increasing interest in ‘nature’ and how it may benefit mental health and well-being.

To understand how the literature defines nature; what the characteristics of the nature intervention are; what mental health and well-being outcomes are being measured; and what the evidence shows, in regard to how nature affects the mental health and well-being of children and adolescents.

A meta-review was conducted, searching three databases for relevant primary and secondary studies, using key search terms including ‘nature’ and ‘mental health’ and ‘mental well-being’. Inclusion criteria included published English-language studies on the child and adolescent population. Authors identified the highest quality evidence from studies meeting the inclusion criteria. Data were extracted and analysed using descriptive content analysis.

Sixteen systematic reviews, two scoping reviews and five good quality cohort studies were included. ‘Nature’ was conceptualised along a continuum (the ‘nature research framework’) into three categories: a human-designed environment with natural elements; a human-designed natural environment; and a natural environment. The nature ‘intervention’ falls into three areas (the ‘nature intervention framework’): access, exposure and engagement with nature, with quantity and quality of nature relevant to all areas. Mental health and well-being outcomes fit along a continuum, with ‘disorder’ at one end and ‘well-being’ at the other. Nature appears to have a beneficial effect, but we cannot be certain of this.

Nature appears to have a beneficial effect on mental health and well-being of children and adolescents. Evidence is lacking on clinical populations, ethnically diverse populations and populations in low- and middle-income countries. Our results should be interpreted considering the limitations of the included studies and confidence in findings.