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.

Observational studies have shown a controversial relationship between dietary fat intake and Alzheimer's disease, and the causal effects are unclear.

To assess the causal effects of total fat, saturated fat and polyunsaturated fat (PUF) intakes on the risk of Alzheimer's disease.

A two-sample Mendelian randomisation analysis was performed using genome-wide association study summary statistics on different types of fat intake from UK Biobank (n = 51 413) and on late-onset Alzheimer's disease (LOAD; 4282 cases, n = 307 112) and all forms of Alzheimer's disease (6281 cases, n = 309 154) from the FinnGen consortium. In addition, a multivariable Mendelian randomisation (MVMR) analysis was conducted to estimate the effects independent of carbohydrate and protein intakes.

Genetically predicted per standard deviation increase in the total fat and saturated fat intakes were associated with 44 and 38% higher risks of LOAD (total fat: odds ratio = 1.44, 95% CI 1.03–2.02; saturated fat: odds ratio = 1.38, 95% CI 1.002–1.90; P = 0.049). The associations remained significant in the MVMR analysis (total fat: odds ratio = 3.31, 95% CI 1.74–6.29; saturated fat: odds ratio = 2.04, 95% CI 1.16–3.59). Total fat and saturated fat intakes were associated with a higher risk of all forms of Alzheimer's disease in the MVMR analysis (total fat: odds ratio = 2.09, 95% CI 1.22–3.57; saturated fat: odds ratio = 1.60, 95% CI 1.01–2.52). The PUF intake was not associated with LOAD or all forms of Alzheimer's disease.

This study indicated that total dietary fat intake, especially saturated fat, contributed to the risk of Alzheimer's disease, and the effects were independent of other nutrients. These findings informed prevention strategies and management for Alzheimer's disease directly towards reducing dietary saturated fat intake.

Systemic changes in multiple diseases may influence the onset of dementia. However, the specific temporality between exposure diseases and dementia remains uncertain.

By characterising the full spectrum of temporal disease trajectories before dementia, this study aims to yield a global picture of precursor diseases to dementia and to provide detailed instructions for risk management and primary prevention of dementia.

Using the multicentre, community-based prospective UK Biobank, we constructed disease trajectories before dementia utilising the phenome-wide association analysis, paired directional test and association quantification. Stratified disease trajectories were constructed by dementia subtypes, gender, age of diagnosis and Apolipoprotein E (ApoE) status, respectively.

Our study population comprised 434 266 participants without baseline dementia and 4638 individuals with all-cause dementia. In total, 1253 diseases were extracted as potential components of the disease trajectory before dementia. We identified three clusters of disease trajectories preceding all-cause dementia, initiated by circulatory, metabolic and respiratory diseases occurring approximately 5–15 years before dementia. Cerebral infarction or chronic renal failure following chronic ischaemic heart disease was the specific trajectory before vascular dementia. Apolipoprotein E (ApoE) ε4 non-carriers exhibited more complex trajectories compared with carriers. Lipid metabolism disorders remained in the trajectories regardless of dementia subtypes, gender, age of diagnosis and ApoE status.

This study provides a comprehensive view of the longitudinal disease trajectories before dementia and highlights the potential targets of midlife cardiometabolic dysfunction for dementia screening and prevention.

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.