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.

Delirium is a severe neuropsychiatric syndrome caused by physical illness, associated with high mortality. Understanding risk factors for delirium is key to targeting prevention and screening. Whether severe mental illness (SMI) predisposes people to delirium is not known. We aimed to establish whether pre-existing SMI diagnosis is associated with higher risk of delirium diagnosis and mortality following delirium diagnosis.

A retrospective cohort and nested case–control study using linked primary and secondary healthcare databases from 2000–2017. We identified people diagnosed with SMI, matched to non-SMI comparators. We compared incidence of delirium diagnoses between people with SMI diagnoses and comparators, and between SMI subtypes; schizophrenia, bipolar disorder and ‘other psychosis’. We compared 30-day mortality following a hospitalisation involving delirium between people with SMI diagnoses and comparators, and between SMI subtypes.

We identified 20 566 people with SMI diagnoses, matched to 71 374 comparators. Risk of delirium diagnosis was higher for all SMI subtypes, with a higher risk conferred by SMI in the under 65-year group, (aHR:7.65, 95% CI 5.45–10.7, ⩾65-year group: aHR:3.35, 95% CI 2.77–4.05). Compared to people without SMI, people with an SMI diagnosis overall had no difference in 30-day mortality following a hospitalisation involving delirium (OR:0.66, 95% CI 0.38–1.14).

We found an association between SMI and delirium diagnoses. People with SMI may be more vulnerable to delirium when in hospital than people without SMI. There are limitations to using electronic healthcare records and further prospective study is needed to confirm these findings.

People with schizophrenia-spectrum and bipolar disorders (severe mental illnesses; ‘SMI’) experience excess mortality. Our aim was to explore longer-term trends in mortality, including the COVID-19 pandemic period, with a focus on additional vulnerabilities (psychiatric comorbidities and race/ ethnicity) in SMI.

Retrospective cohort study using electronic health records from secondary mental healthcare, covering a UK region of 1.3 million people. Mortality trends spanning fourteen years, including the COVID-19 pandemic, were assessed in adults with clinician-ascribed ICD-10 diagnoses for schizophrenia-spectrum and bipolar disorders.

The sample comprised 22 361 people with SMI with median follow-up of 10.6 years. Standardized mortality ratios were more than double the population average pre-pandemic, increasing further during the pandemic, particularly in those with SMI and psychiatric comorbidities. Mortality risk increased steadily among people with SMI and comorbid depression, dementia, substance use disorders and anxiety over 13-years, increasing further during the pandemic. COVID-19 mortality was elevated in people with SMI and comorbid depression (sub-Hazard Ratio: 1.48 [95% CI 1.03–2.13]), dementia (sHR:1.96, 1.26–3.04) and learning disabilities (sHR:2.30, 1.30–4.06), compared to people with only SMI. COVID-19 mortality risk was similar for minority ethnic groups and White British people with SMI. Elevated all-cause mortality was evident in Black Caribbean (adjusted Rate Ratio: 1.40, 1.11–1.77) and Black African people with SMI (aRR: 1.59, 1.07–2.37) during the pandemic relative to earlier years.

Mortality has increased over time in people with SMI. The pandemic exacerbated pre-existing trends. Actionable solutions are needed which address wider social determinants and address disease silos.

While antipsychotic medication reduces the risk of relapse for patients with schizophrenia, high prevalence of adverse effects results in low adherence. Lower doses of antipsychotics have been associated with increased level of function but also with increased risk of relapse. This study presents findings from a specialized deprescribing clinic. In addition, we aim to identify clinical predictors for relapse.

Patients diagnosed with schizophrenia were referred to the clinic, which offers a six-month guided tapering program. Antipsychotic dose was reduced by 10% every four weeks. Patients were monitored closely for symptom progression or decrease in level of function, with defined cut-offs prompting a pause in or cessation of dose reduction.

After 12 months, the antipsychotic dose was reduced from 404 (±320 mg) to 255 (±236 mg) chlorpromazine equivalent. Of the 88 patients included, 22 (27%) experienced relapse during the six-month tapering period, while 29 (37%) experienced relapse at the 12-month follow-up visit and nine patients were antipsychotic free. Patients who remained stable experienced a slightly increased level of functioning and markedly fewer side effects (p < 0.001). Following relapse, patients were clinically stabilized and showed an improved attitude toward antipsychotic medication. The predictive models were weak.

We show that most patients undergoing guided antipsychotic tapering remained stable after one year and improved in level of function, while most patients who relapsed were quickly stabilized. Our inability to create strong predictive models could be due to limitations in the study design, warranting future studies exploring tapering of antipsychotics in patients with schizophrenia.

Severe mental illness (SMI), which includes schizophrenia, schizoaffective disorder and bipolar disorder, has profound health impacts, even in the elderly.

To evaluate relative risk of hospital admission and length of hospital stay for physical illness in elders with SMI.

To construct a population-based retrospective cohort observed from April 2007 to March 2016, data from a case registry with full but de-identified electronic health records were retrieved for patients of the South London and Maudsley NHS Foundation Trust, the single secondary mental healthcare service provider in south-east London. We compared participants with SMI aged >60 years old with the general population of the same age and residing in the same areas through data linkage by age-, sex- and fiscal-year-standardised admission ratios (SARs) for primary diagnoses at hospital discharge. Furthermore, we compared the duration of hospital stay with an age-, sex- and cause-of-admission-matched random group by linear regression for major causes of admission.

In total, records for 4175 older people with SMI were obtained, relating to 10 342 admission episodes, showing an overall SAR for all physical illnesses of 5.15 (95% CI: 5.05, 5.25). Among the top causes of admission, SARs ranged from 3.87 for circulatory system disorders (ICD-10 codes: I00–I99) to 6.99 for genitourinary system or urinary conditions (N00–N39). Specifically, the diagnostic group of ‘symptoms, signs and findings, not elsewhere classified’ (R00–R99) had an elevated SAR of 6.56 (95% CI: 6.22, 6.90). Elders with SMI also had significantly longer hospital stays than their counterparts in the general population, especially for digestive system illnesses (K00–K93), after adjusting for confounding.

Poorer overall physical health and specific patterns were identified in elders with SMI.

Treatment resistance is a major challenge in psychiatric disorders. Early detection of potential future resistance would improve prognosis by reducing the delay to appropriate treatment adjustment and recovery. Here, we sought to determine whether neurodevelopmental markers can predict therapeutic response.

Healthy controls (N = 236), patients with schizophrenia (N = 280) or bipolar disorder (N = 78) with a known therapeutic outcome, were retrospectively included. Age, sex, education, early developmental abnormalities (obstetric complications, height, weight, and head circumference at birth, hyperactivity, dyslexia, epilepsy, enuresis, encopresis), neurological soft signs (NSS), and ages at first subjective impairment, clinical symptoms, treatment, and hospitalization, were recorded. A supervised algorithm leveraged NSS and age at first clinical signs to classify between resistance and response in schizophrenia.

Developmental abnormalities were more frequent in schizophrenia and bipolar disorder than in controls. NSS significantly differed between controls, responsive, and resistant participants with schizophrenia (5.5 ± 3.0, 7.0 ± 4.0, 15.0 ± 6.0 respectively, p = 3 × 10−10) and bipolar disorder (5.5 ± 3.0, 8.3 ± 3.0, 12.5 ± 6.0 respectively, p < 1 × 10−10). In schizophrenia, but not in bipolar disorder, age at first subjective impairment was three years lower, and age at first clinical signs two years lower, in resistant than responsive subjects (p = 2 × 10−4 and p = 9 × 10−3, respectively). Age at first clinical signs and NSS accurately predicted treatment response in schizophrenia (area-under-curve: 77 ± 8%, p = 1 × 10−14).

Neurodevelopmental features such as NSS and age of clinical onset provide a means to identify patients who may require rapid treatment adaptation.

Studies suggest severe mental disorders (SMDs), such as schizophrenia, major depressive disorder and bipolar disorder, are associated with common alterations in brain activity, albeit with a graded level of impairment. However, discrepancies between study findings likely to results from both small sample sizes and the use of different functional magnetic resonance imaging (fMRI) tasks. To address these issues, data-driven meta-analytic approach designed to identify homogeneous brain co-activity patterns across tasks was conducted to better characterize the common and distinct alterations between these disorders.

A hierarchical clustering analysis was conducted to identify groups of studies reporting similar neuroimaging results, independent of task type and psychiatric diagnosis. A traditional meta-analysis (activation likelihood estimation) was then performed within each of these groups of studies to extract their aberrant activation maps.

A total of 762 fMRI study contrasts were targeted, comprising 13 991 patients with SMDs. Hierarchical clustering analysis identified 5 groups of studies (meta-analytic groupings; MAGs) being characterized by distinct aberrant activation patterns across SMDs: (1) emotion processing; (2) cognitive processing; (3) motor processes, (4) reward processing, and (5) visual processing. While MAG1 was mostly commonly impaired, MAG2 was more impaired in schizophrenia, while MAG3 and MAG5 revealed no differences between disorder. MAG4 showed the strongest between-diagnoses differences, particularly in the striatum, posterior cingulate cortex, and ventromedial prefrontal cortex.

SMDs are characterized mostly by common deficits in brain networks, although differences between disorders are also present. This study highlights the importance of studying SMDs simultaneously rather than independently.

This systematic review aimed to review therapeutic patient education (TPE) programmes in managing psychiatric disorders, considering the diversity in delivering agents, intervention formats, targeted skills, and therapeutic outcomes.

Comprehensive database searches, including Web of Science, PubMed, and COCHRANE, were conducted from September 2019 to January 2023, yielding 514 unique records, with 33 making it through rigorous evaluation for full-text review. Eleven studies met the inclusion criteria, focusing on various psychiatric disorders such as depression, bipolar disorder, psychosis, and multiple serious mental illnesses. A total of 38 studies were included from our previous review to supplement the current database search.

TPE programmes exhibited diversity in delivering agents and intervention formats, with a notable presence of multidisciplinary teams and various professionals. The interventions prioritized coping strategies and disease management techniques, though the extent varied based on the disorder. Effectiveness was heterogeneous across studies; some interventions showed significant benefits in areas such as symptom management, coping, and functional improvement, while others reported no significant outcomes.

The findings underscore the potential of TPE in psychiatric care, revealing its multifaceted nature and varied impact. TPE not only addresses deficits but also leverages patients’ existing strengths and capabilities. Despite the reported benefits, a portion of the interventions lacked statistical significance, indicating the necessity for continuous refinement and evaluation.

The ways in which perceived harm due to substance use affects relationships between psychotic and suicidal experiences are poorly understood. The goal of the current study was to redress this gap by investigating the moderating effects of harm due to substance use on pathways involving positive psychotic symptoms, the perceived cognitive-emotional sequelae of those symptoms, and suicidal ideation.

The design was cross-sectional. Mediation and moderated mediation pathways were tested. The predictor was severity of positive psychotic symptoms. Cognitive interpretative and emotional characteristics of both auditory hallucinations and delusions were mediators. Suicidal ideation was the outcome variable. General symptoms associated with severe mental health problems were statistically controlled for.

There was evidence of an indirect pathway between positive psychotic symptom severity and suicidal ideation via cognitive interpretation and emotional characteristics of both auditory hallucinations and delusions. Harm due to drug use, but not alcohol use, moderated the indirect pathway involving delusions such that it was most prominent when harm due to drug use was at medium-to-high levels. The components of suicidal ideation that were most strongly affected by this moderated indirect pathway were active intent, passive desire, and lack of deterrents.

From both scientific and therapy development perspectives, it is important to understand the complex interplay between, not only the presence of auditory hallucinations and delusions, but the ensuing cognitive and emotional consequences of those experiences which, when combined with harm associated with substance use, in particular drug use, can escalate suicidal thoughts and acts.

3q29 deletion syndrome (3q29del) is a rare (~1:30 000) genomic disorder associated with a wide array of neurodevelopmental and psychiatric phenotypes. Prior work by our team identified clinically significant executive function (EF) deficits in 47% of individuals with 3q29del; however, the nuances of EF in this population have not been described.

We used the Behavior Rating Inventory of Executive Function (BRIEF) to perform the first in-depth assessment of real-world EF in a cohort of 32 individuals with 3q29del (62.5% male, mean age = 14.5 ± 8.3 years). All participants were also evaluated with gold-standard neuropsychiatric and cognitive assessments. High-resolution structural magnetic resonance imaging was performed on a subset of participants (n = 24).

We found global deficits in EF; individuals with 3q29del scored higher than the population mean on the BRIEF global executive composite (GEC) and all subscales. In total, 81.3% of study subjects (n = 26) scored in the clinical range on at least one BRIEF subscale. BRIEF GEC T scores were higher among 3q29del participants with a diagnosis of attention deficit/hyperactivity disorder (ADHD), and BRIEF GEC T scores were associated with schizophrenia spectrum symptoms as measured by the Structured Interview for Psychosis-Risk Syndromes. BRIEF GEC T scores were not associated with cognitive ability. The BRIEF-2 ADHD form accurately (sensitivity = 86.7%) classified individuals with 3q29del based on ADHD diagnosis status. BRIEF GEC T scores were correlated with cerebellar white matter and subregional cerebellar cortex volumes.

Together, these data expand our understanding of the phenotypic spectrum of 3q29del and identify EF as a core feature linked to both psychiatric and neuroanatomical features of the syndrome.

Although clozapine is the most effective antipsychotic for people with treatment-resistant schizophrenia (TRS), only 40% of people with TRS respond, and there is limited evidence for augmentation agents. Cannabidiol (CBD) reduces positive symptoms in individuals with schizophrenia, but no trials have specifically examined its efficacy in those with clozapine-resistant schizophrenia.

To examine the clinical efficacy of CBD augmentation in people with clozapine-resistant schizophrenia.

This is a 12-week randomised, placebo-controlled, double-blind, parallel-group trial (registration number: ACTRN12622001112752). We will recruit 88 individuals with clozapine-resistant schizophrenia, randomised (1:1) to 1000 mg daily CBD versus placebo. Eligible individuals will be aged between 18 and 64 years, fulfil DSM-IV criteria for schizophrenia or schizoaffective disorder, have a total PANSS (Positive and Negative Syndrome Scale) score ≥60, have received oral clozapine for at least 18 weeks and have a clozapine level of >350 ng/mL. Interim analyses will be conducted at 25, 50 and 75% recruitment; these will also provide an opportunity to reallocate participants dependent on conditional power. The primary endpoint will be the difference in PANSS positive scores at the end of week 12. Secondary endpoints include depression, anxiety, sleep, quality of life, alcohol consumption, change in weight and metabolic syndrome components, and neurocognitive measures, as well as safety and tolerability.

Novel treatments for clozapine-resistant schizophrenia are urgently needed. If found to be effective, CBD may have a role as a novel and safe adjunct to clozapine.

While inflammation is associated with cognitive impairment in severe mental illnesses (SMI), there is substantial heterogeneity and evidence of transdiagnostic subgroups across schizophrenia (SZ) and bipolar (BD) spectrum disorders. There is however, limited knowledge about the longitudinal course of this relationship.

Systemic inflammation (C-Reactive Protein, CRP) and cognition (nine cognitive domains) was measured from baseline to 1 year follow-up in first treatment SZ and BD (n = 221), and healthy controls (HC, n = 220). Linear mixed models were used to evaluate longitudinal changes separately in CRP and cognitive domains specific to diagnostic status (SZ, BD, HC). Hierarchical clustering was applied on the entire sample to investigate the longitudinal course of transdiagnostic inflammatory-cognitive subgroups.

There were no case-control differences or change in CRP from baseline to follow-up. We confirm previous observations of case-control differences in cognition at both time-points and domain specific stability/improvement over time regardless of diagnostic status. We identified transdiagnostic inflammatory-cognitive subgroups at baseline with differing demographics and clinical severity. Despite improvement in cognition, symptoms and functioning, the higher inflammation – lower cognition subgroup (75% SZ; 48% BD; 38% HC) had sustained inflammation and lower cognition, more symptoms, and lower functioning (SMI only) at follow-up. This was in comparison to a lower inflammation – higher cognition subgroup (25% SZ, 52% BD, 62% HC), where SMI participants showed cognitive functioning at HC level with a positive clinical course.

Our findings support heterogenous and transdiagnostic inflammatory-cognitive subgroups that are stable over time, and may benefit from targeted interventions.

Major depressive disorder (MDD) is a leading cause of disability and premature mortality. This study compared the overall survival (OS) between patients with MDD and non-MDD controls stratified by gender, age, and comorbidities.

This nationwide population-based cohort study utilized longitudinal patient data (01/01/2010 – 12/31/2020) from the Hungarian National Health Insurance Fund database, which contains healthcare service data for the Hungarian population. Patients with MDD were selected and matched 1:1 to those without MDD using exact matching. The rates of conversion from MDD to bipolar disorder (BD) or schizophrenia were also investigated.

Overall, 471,773 patients were included in each of the matched MDD and non-MDD groups. Patients with MDD had significantly worse OS than non-MDD controls (hazard ratio [HR] = 1.50; 95% CI: 1.48−1.51; males HR = 1.69, 95% CI: 1.66–1.72; females HR = 1.40, 95% CI: 1.38–1.42). The estimated life expectancy of patients with MDD was 7.8 and 6.0 years less than that of controls aged 20 and 45 years, respectively. Adjusted analyses based on the presence of baseline comorbidities also showed that patients with MDD had worse survival than non-MDD controls (adjusted HR = 1.29, 95% CI: 1.28–1.31). After 11 years of follow-up, the cumulative conversions from MDD to BD and schizophrenia were 6.8 and 3.4%, respectively. Converted patients had significantly worse OS than non-converted patients.

Compared with the non-MDD controls, a higher mortality rate in patients with MDD, especially in those with comorbidities and/or who have converted to BD or schizophrenia, suggests that early detection and personalized treatment of MDD may reduce the mortality in patients diagnosed with MDD.