A youth mental health crisis is considered one of the great challenges of our time, and research and clinical services in child and adolescent psychiatry have become a priority for governments and funders. Academic leadership is needed to drive forward research. It is not clear how many senior academic leadership posts (professorships) there are in child and adolescent psychiatry, nor how this benchmarks against a similarly sized medical specialty.

This study aimed to determine the number of professorships in child and adolescent psychiatry in the UK and Ireland compared to a similarly sized specialty. A secondary aim was to identify the number of clinical trials registered for mental and behavioural disorders in children.

We identified registered specialists in child and adolescent psychiatry and a similarly sized specialty who held full professorships in medical schools. We searched the International Standard Randomised Controlled Trial Number (ISRCTN) and ClinicalTrials.gov for trials.

As of 23 March 2023, there were 1725 doctors on the General Medical Council's (GMC) specialist register in child and adolescent psychiatry. The closest specialty in terms of number of registered specialists was neurology (N = 1724). We identified 24 professors in child and adolescent psychiatry across the UK and Ireland, compared to 124 in neurology. For every intervention trial registered for mental and behavioural disorders in children, there were approximately ten trials registered for diseases of the nervous system.

Despite equivalent numbers of medical specialists in child and adolescent psychiatry and neurology, there is a striking disparity in the number of professorship appointments. While young peoples’ mental health has, ostensibly, become a priority for policy-makers and funders, this is not reflected in medical professorship appointments. The paucity of senior academic child and adolescent psychiatrists has real-world implications for training, research, innovation and service development in mental health services.

Anxiety symptoms are elevated among people with joint hypermobility. The underlying neural mechanisms are attributed theoretically to effects of variant connective tissue on the precision of interoceptive representations contributing to emotions.

To investigate the neural correlates of anxiety and hypermobility using functional neuroimaging.

We used functional magnetic resonance neuroimaging to quantify regional brain responses to emotional stimuli (facial expressions) in people with generalised anxiety disorder (GAD) (N = 30) and a non-anxious comparison group (N = 33). All participants were assessed for joint laxity and were classified (using Brighton Criteria) for the presence and absence of hypermobility syndrome (HMS: now considered hypermobility spectrum disorder).

Participants with HMS showed attenuated neural reactivity to emotional faces in specific frontal (inferior frontal gyrus, pre-supplementary motor area), midline (anterior mid and posterior cingulate cortices) and parietal (precuneus and supramarginal gyrus) regions. Notably, interaction between HMS and anxiety was expressed in reactivity of the left amygdala (a region implicated in threat processing) and mid insula (primary interoceptive cortex) where activity was amplified in people with HMS with GAD. Severity of hypermobility in anxious, compared with non-anxious, individuals correlated with activity within the anterior insula (implicated as the neural substrate linking anxious feelings to physiological state). Amygdala-precuneus functional connectivity was stronger in participants with HMS, compared with non-HMS participants.

The predisposition to anxiety in people with variant connective tissue reflects dynamic interactions between neural centres processing threat (amygdala) and representing bodily state (insular and parietal cortices). Correspondingly, interventions to regulate amygdala reactivity while enhancing interoceptive precision may have therapeutic benefit for symptomatic hypermobile individuals.

Reliable and specific biomarkers that can distinguish autism spectrum disorders (ASDs) from commonly co-occurring attention-deficit/hyperactivity disorder (ADHD) are lacking, causing misses and delays in diagnosis, and reducing access to interventions and quality of life.

To examine whether an innovative, brief (1-min), videogame method called Computerised Assessment of Motor Imitation (CAMI), can identify ASD-specific imitation differences compared with neurotypical children and children with ADHD.

This cross-sectional study used CAMI alongside standardised parent-report (Social Responsiveness Scale, Second Edition) and observational measures of autism (Autism Diagnostic Observation Schedule-Second Edition; ADOS-2), ADHD (Conners) and motor ability (Physical and Neurological Examination for Soft Signs). The sample comprised 183 children aged 7–13 years, with ADHD (without ASD), with ASD (with and without ADHD) and who were neurotypical.

Regardless of co-occurring ADHD, children with ASD showed poorer CAMI performance than neurotypical children (P < 0.0001; adjusted R2 = 0.28), whereas children with ADHD and neurotypical children showed similar CAMI performance. Receiver operating curve and support vector machine analyses showed that CAMI distinguishes ASD from both neurotypical children (80% true positive rate) and children with ADHD (70% true positive rate), with a high success rate significantly above chance. Among children with ASD, poor CAMI performance was associated with increased autism traits, particularly ADOS-2 measures of social affect and restricted and repetitive behaviours (adjusted R2 = 0.23), but not with ADHD traits or motor ability.

Four levels of analyses confirm that poor imitation measured by the low-cost and scalable CAMI method specifically distinguishes ASD not only from neurotypical development, but also from commonly co-occurring ADHD.

Nearly 3% of adults have attention-deficit and hyperactivity disorder (ADHD), although in the UK, most are undiagnosed. Adults with ADHD on average experience poorer educational and employment outcomes, worse physical and mental health and are more likely to die prematurely. No studies have yet used mortality data to examine the life expectancy deficit experienced by adults with diagnosed ADHD in the UK or worldwide.

This study used the life-table method to calculate the life-expectancy deficit for people with diagnosed ADHD using data from UK primary care.

A matched cohort study using prospectively collected primary care data (792 general practices, 9 561 450 people contributing eligible person-time from 2000–2019). We identified 30 039 people aged 18+ with diagnosed ADHD, plus a comparison group of 300 390 participants matched (1:10) by age, sex and primary care practice. We used Poisson regression to estimate age-specific mortality rates, and life tables to estimate life expectancy for people aged 18+ with diagnosed ADHD.

Around 0.32% of adults in the cohort had an ADHD diagnosis, ~1 in 9 of all adults with ADHD. Diagnoses of common physical and mental health conditions were more common in adults with diagnosed ADHD than the comparison group. The apparent reduction in life expectancy for adults with diagnosed ADHD relative to the general population was 6.78 years (95% CI: 4.50 to 9.11) for males, and 8.64 years (95% CI: 6.55 to 10.91) for females.

Adults with diagnosed ADHD are living shorter lives than they should. We believe that this is likely caused by modifiable risk factors and unmet support and treatment needs in terms of both ADHD and co-occurring mental and physical health conditions. This study included data from adults with diagnosed ADHD; the results may not generalise to the entire population of adults with ADHD, the vast majority of whom are undiagnosed.

Intergenerational transmission of mental disorders has been well established, but it is unclear whether exposure to a child's mental disorder increases parents' subsequent risk of mental disorders.

We examined the association of mental disorders in children with their parents' subsequent mental disorders.

In this population-based cohort study, we included all individuals with children born in Finland or Denmark in 1990–2010. Information about mental disorders was acquired from national registers. The follow-up period began when the parent's eldest child was 5 years old (for ICD-10 codes F10–F60) or 1 year old (for codes F70–F98) and ended on 31 December 2019 or when the parent received a mental disorder diagnosis, died, or emigrated from Finland or Denmark. The associations of mental disorders in children with their parents' subsequent mental disorders were examined using Cox proportional hazards models.

The study cohort included 1 651 723 parents. In total, 248 328 women and 250 763 men had at least one child who had been diagnosed with a mental disorder. The risk of a parent receiving a mental disorder diagnosis was higher among those who had a child with a mental disorder compared with those who did not. For both parents, the hazard ratios were greatest in the first 6 months after the child's diagnosis (hazard ratio 2.04–2.54), followed by a subtle decline in the risk (after 2 years, the hazard ratio was 1.33–1.77).

Mental disorders in children are associated with a greater risk of subsequent mental disorders among their parents. Additional support is needed for parents whose children have been recently diagnosed with a mental disorder.

Suicide in women in the UK is highest among those in midlife. Given the unique changes in biological, social and economic risk factors experienced by women in midlife, more information is needed to inform care.

To investigate rates, characteristics and outcomes of self-harm in women in midlife compared to younger women and identify differences within the midlife age-group.

Data on women aged 40–59 years from the Multicentre Study of Self-harm in England from 2003 to 2016 were used, including mortality follow-up to 2019, collected via specialist assessments and/or emergency department records. Trends were assessed using negative binomial regression models. Comparative analysis used chi-square tests of association. Self-harm repetition and suicide mortality analyses used Cox proportional hazards models.

The self-harm rate in midlife women was 435 per 100 000 population and relatively stable over time (incident rate ratio (IRR) 0.99, p < 0.01). Midlife women reported more problems with finances, alcohol and physical and mental health. Suicide was more common in the oldest midlife women (hazard ratio 2.20, p < 0.01), while psychosocial assessment and psychiatric inpatient admission also increased with age.

Addressing issues relating to finances, mental health and alcohol misuse, alongside known social and biological transitions, may help reduce self-harm in women in midlife. Alcohol use was important across midlife while physical health problems and bereavement increased with age. Despite receiving more intensive follow-up care, suicide risk in the oldest women was elevated. Awareness of these vulnerabilities may help inform clinicians’ risk formulation and safety planning.

Accurate diagnosis of bipolar disorder (BPD) is difficult in clinical practice, with an average delay between symptom onset and diagnosis of about 7 years. A depressive episode often precedes the first manic episode, making it difficult to distinguish BPD from unipolar major depressive disorder (MDD).

We use genome-wide association analyses (GWAS) to identify differential genetic factors and to develop predictors based on polygenic risk scores (PRS) that may aid early differential diagnosis.

Based on individual genotypes from case–control cohorts of BPD and MDD shared through the Psychiatric Genomics Consortium, we compile case–case–control cohorts, applying a careful quality control procedure. In a resulting cohort of 51 149 individuals (15 532 BPD patients, 12 920 MDD patients and 22 697 controls), we perform a variety of GWAS and PRS analyses.

Although our GWAS is not well powered to identify genome-wide significant loci, we find significant chip heritability and demonstrate the ability of the resulting PRS to distinguish BPD from MDD, including BPD cases with depressive onset (BPD-D). We replicate our PRS findings in an independent Danish cohort (iPSYCH 2015, N = 25 966). We observe strong genetic correlation between our case–case GWAS and that of case–control BPD.

We find that MDD and BPD, including BPD-D are genetically distinct. Our findings support that controls, MDD and BPD patients primarily lie on a continuum of genetic risk. Future studies with larger and richer samples will likely yield a better understanding of these findings and enable the development of better genetic predictors distinguishing BPD and, importantly, BPD-D from MDD.

Women with schizophrenia frequently discontinue antipsychotic medications during pregnancy. However, evidence on the risk of postpartum relapse associated with antipsychotic use during pregnancy is lacking.

To investigate the within-individual association between antipsychotic continuation during pregnancy and postpartum relapse in women with schizophrenia.

This retrospective cohort study used data of women with schizophrenia who gave live birth between 2007 and 2018 identified from the National Health Information Database of South Korea. Women were classified according to antipsychotic use patterns during the 12 months before delivery as non-users, discontinuers and continuers. Relapse was defined as admission for psychosis (ICD-10, F20–29). The incidence rate ratio (IRR) for admission for psychosis in the 6-month postpartum period was estimated using conditional Poisson regression, with the reference period set between 2 and 1 years before delivery. Additionally, we calculated the relative risk ratios (RRRs) for the IRRs of different antipsychotic use patterns.

Among the 3026 women included in the analysis (median age 34 years, interquartile range 31–37), the within-individual risk of admission for psychosis in the 6-month postpartum period was 0.56 times (RRR, 95% CI 0.36–0.87) lower in continuers (IRR = 1.31, 95% CI 0.89–1.72) than in discontinuers (IRR = 2.34, 95% CI 1.87–2.91). Among discontinuers, the IRRs of admission for psychosis in the 6-month postpartum period did not change significantly with the timing of discontinuation (trend P = 0.946).

Antipsychotic continuation during pregnancy was associated with a reduced risk of postpartum relapse in women with schizophrenia. Continuing antipsychotics during pregnancy would be recommended after a risk–benefit assessment.

Negative perceptions of mental health professionals can deter individuals from seeking mental healthcare. Given the high burden of mental health globally, it is essential to understand attitudes towards mental health professionals. Social media platforms like Twitter/X provide valuable insights into the views of the general population.

This study aimed to use social media to investigate the (a) public perceptions (positive or negative) of mental health professionals, (b) changes in these perceptions over time and (c) engagement levels with tweets about mental health professionals over time.

We collected all tweets posted in English between 2007 and 2023, containing key terms such as ‘mental health’, ‘psychology’, ‘psychologist’, ‘psychiatry’, ‘psychiatrist’, ‘neurology’ and ‘neurologist’. A total of 1500 tweets were manually classified into categories, which were used in conjunction with semi-supervised machine learning to categorise a large data-set.

For most key terms, there was a higher frequency of positive perceptions compared with negative, with this trend improving over time. However, tweets containing ‘psychiatrist’ exhibited a higher proportion of negative perceptions (n = 4872, 39.52% negative v. n = 1972, 15.99% positive before 2020). After 2020, the gap narrowed, yet negative perceptions continued to dominate (n = 5505, 36.10% negative v. n = 3472, 22.77% positive).

Overall, positive perceptions of mental health and mental health professionals increased over time. However, ‘psychiatrist’ had a consistently higher proportion of negative perceptions. This study underscores the need to improve public perception of psychiatrists, and demonstrates the potential of using Twitter/X to better understand public attitudes and reduce stigma associated with accessing mental health services.

Anxiety disorders and treatment-resistant major depressive disorder (TRD) are often comorbid. Studies suggest ketamine has anxiolytic and antidepressant properties.

To investigate if subcutaneous racemic ketamine, delivered twice weekly for 4 weeks, reduces anxiety in people with TRD.

The Ketamine for Adult Depression Study was a multisite 4-week randomised, double-blind, active (midazolam)-controlled trial. The study initially used fixed low dose ketamine (0.5 mg/kg, cohort 1), before protocol revision to flexible, response-guided dosing (0.5–0.9 mg/kg, cohort 2). This secondary analysis assessed anxiety using the Hamilton Anxiety (HAM-A) scale (primary measure) and ‘inner tension’ item 3 of the Montgomery–Åsberg Depression Rating Scale (MADRS), at baseline, 4 weeks (end treatment) and 4 weeks after treatment end. Analyses of change in anxiety between ketamine and midazolam groups included all participants who received at least one treatment (n = 174), with a mixed effects repeated measures model used to assess the primary anxiety measure. The trial was registered at www.anzctr.org.au (ACTRN12616001096448).

In cohort 1 (n = 68) the reduction in HAM-A score was not statistically significant: −1.4 (95% CI [−8.6, 3.2], P = 0.37), whereas a significant reduction was seen for cohort 2 (n = 106) of −4.0 (95% CI [−10.6, −1.9], P = 0.0058), favouring ketamine over midazolam. These effects were mediated by total MADRS and were not maintained at 4 weeks after treatment end. MADRS item 3 was also significantly reduced in cohort 2 (P = 0.026) but not cohort 1 (P = 0.96).

Ketamine reduces anxiety in people with TRD when administered subcutaneously in adequate doses.

An improved understanding of the factors associated with self-harm in young people who die by suicide can inform suicide prevention measures.

To describe sociodemographic and clinical characteristics and service utilisation related to self-harm in a national sample of young people who died by suicide.

We carried out a descriptive study of self-harm in a national consecutive case series (N = 544) of 10- to 19-year-olds who died by suicide over 3 years (2014–2016) in the UK as identified from national mortality data. Information was collected from coroner inquest hearings, child death investigations, criminal justice system and National Health Service serious incident reports.

Almost half (49%) of these young people had harmed themselves at some point in their lives, a quarter (26%) in the 3 months before death. Girls were twice as likely as boys to have recent self-harm (40 v. 20%; P < 0.001). Compared to the no self-harm group, young people with recent self-harm were more likely to have a mental illness diagnosis (63 v. 23%; P < 0.001); misused alcohol (19 v. 9%; P = 0.07); experienced physical, sexual or emotional abuse (17 v. 3%; P < 0.01); and recent life adversity (95 v. 75%; P < 0.001). Furthermore, they were more likely to be in contact with mental health services (60 v. 10%), or emergency departments or general physicians for a mental health condition (52 v. 10%) in the 3 months before death.

Presentation to services in young people who self-harm is an important opportunity to intervene through comprehensive psychosocial assessment and treatment of underlying conditions.

Previous economic evidence about interventions for schizophrenia is outdated, non-transparent and/or limited to a specific clinical context.

We developed a de novo discrete event simulation (DES) model for estimating the cost-effectiveness of interventions in schizophrenia in the UK.

The DES model was developed based on the structure of previous models, populated with demographic, clinical and cost data from the UK, and antipsychotics' effects from recent network meta-analyses. We simulated treatment pathways for patients with first-episode schizophrenia including events such as relapse, remission, treatment discontinuation, cardiovascular disease and death and estimated costs (2020£) taking the National Health Service perspective and quality-adjusted life years (QALYs) over ten years. Using the model, we ranked ten first-line antipsychotics based on their QALYs and cost-effectiveness.

Amisulpride was associated with the highest QALYs, followed by risperidone long-acting injection (LAI), aripiprazole-LAI (6.121, 6.084, 6.070, respectively) and others (5.947–6.058). The most cost-effective antipsychotics were amisulpride, olanzapine and risperidone-LAI, with total probability of rankings of 1, ≤2, ≤3, that is, 95%, 89%, 80%, respectively; meanwhile, the least cost-effective were cariprazine, lurasidone and quetiapine, with total probability of rankings of 10, ≥9, ≥8, that is, 96%, 92%, 81%, respectively. Results were robust across sensitivity analyses and influenced primarily by relapse relevant parameters.

Our findings suggest amisulpride (or risperidone-LAI where oral treatment is inappropriate) as the best overall first-line option based on QALYs and cost-effectiveness. Our ranking may be used to guide decision-making between antipsychotics. Our model is open source and could be applied to the other settings.

Trace amine-associated receptor 1 (TAAR1) agonists offer a new approach, but there is uncertainty regarding their effects, exact mechanism of action and potential role in treating psychosis.

To evaluate the available evidence on TAAR1 agonists in psychosis, using triangulation of the output of living systematic reviews (LSRs) of animal and human studies, and provide recommendations for future research prioritisation.

This study is part of GALENOS (Global Alliance for Living Evidence on aNxiety, depressiOn and pSychosis). In the triangulation process, a multidisciplinary group of experts, including those with lived experience, met and appraised the first co-produced living systematic reviews from GALENOS, on TAAR1 agonists.

The animal data suggested a potential antipsychotic effect, as TAAR1 agonists reduced locomotor activity induced by pro-psychotic drug treatment. Human studies showed few differences for ulotaront and ralmitaront compared with placebo in improving overall symptoms in adults with acute schizophrenia (four studies, n = 1291 participants, standardised mean difference (SMD) 0.15, 95% CI −0.05 to 0.34). Large placebo responses were seen in ulotaront phase three trials. Ralmitaront was less efficacious than risperidone (one study, n = 156 participants, SMD = −0.53, 95% CI −0.86 to −0.20). The side-effect profile of TAAR1 agonists was favourable compared with existing antipsychotics. Priorities for future studies included (a) using different animal models of psychosis with greater translational validity; (b) animal and human studies with wider outcomes including cognitive and affective symptoms and (c) mechanistic studies and investigations of other potential applications, such as adjunctive treatments and long-term outcomes. Recommendations for future iterations of the LSRs included (a) meta-analysis of individual human participant data, (b) including studies that used different methodologies and (c) assessing other disorders and symptoms.

This co-produced, international triangulation examined the available evidence and developed recommendations for future research and clinical applications for TAAR1 agonists in psychosis. Broader challenges included difficulties in assessing the risk of bias, reproducibility, translation and interpretability of animal models to clinical outcomes, and a lack of individual and clinical characteristics in the human data. The research will inform a separate, independent prioritisation process, led by lived experience experts, to prioritise directions for future research.

Contemporary data relating to antipsychotic prescribing in UK primary care for patients diagnosed with severe mental illness (SMI) are lacking.

To describe contemporary patterns of antipsychotic prescribing in UK primary care for patients diagnosed with SMI.

Cohort study of patients with an SMI diagnosis (i.e. schizophrenia, bipolar disorder, other non-organic psychoses) first recorded in primary care between 2000 and 2017 derived from Clinical Practice Research Datalink. Patients were considered exposed to antipsychotics if prescribed at least one antipsychotic in primary care between 2000 and 2019. We compared characteristics of patients prescribed and not prescribed antipsychotics; calculated annual prevalence rates for antipsychotic prescribing; and computed average daily antipsychotic doses stratified by patient characteristics.

Of 309 378 patients first diagnosed with an SMI in primary care between 2000 and 2017, 212,618 (68.7%) were prescribed an antipsychotic between 2000 and 2019. Antipsychotic prescribing prevalence was 426 (95% CI, 420–433) per 1000 patients in the year 2000, reaching a peak of 550 (547–553) in 2016, decreasing to 470 (468–473) in 2019. The proportion prescribed antipsychotics was higher among patients diagnosed with schizophrenia (81.0%) than with bipolar disorder (64.6%) and other non-organic psychoses (65.7%). Olanzapine, quetiapine, risperidone and aripiprazole accounted for 78.8% of all antipsychotic prescriptions. Higher mean olanzapine equivalent total daily doses were prescribed to patients with the following characteristics: schizophrenia diagnosis, ethnic minority status, male gender, younger age and greater relative deprivation.

Antipsychotic prescribing is dominated by olanzapine, quetiapine, risperidone and aripiprazole. We identified potential disparities in both the receipt and prescribed doses of antipsychotics across subgroups. To inform efforts to optimise prescribing and ensure equity of care, further research is needed to understand why certain groups are prescribed higher doses and are more likely to be treated with long-acting injectable antipsychotics compared with others.

Studies in cognitively normal individuals on associations between psychiatric symptomatology and incident dementia have not reliably differentiated psychiatric syndromes from neuropsychiatric symptoms (NPS) that represent neurodegeneration. Conventional modelling often overlooks symptom natural history. Mild behavioural impairment (MBI) is a syndrome that leverages later-life emergent and persistent NPS to identify a high-risk group for incident dementia.

We aimed to explore associations of MBI, and conventionally-measured NPS (NPS-not-MBI), with incident dementia in cognitively normal individuals and the cognitively normal subset with subjective cognitive decline (SCD).

Using National Alzheimer's Coordinating Center data, MBI was operationalised by the absence of past psychiatric disorders (symptom emergence) and the presence of symptoms at >2/3 of pre-dementia visits (symptom persistence). Kaplan–Meier survival curves and Cox proportional hazards regressions modelled dementia incidence across NPS groups and MBI domains, adjusted for age, gender, education, race, APOE-ε4, and cognitive status.

The sample comprised 1408 MBI (age 75.2 ± 9.5; 54.3% female), 5625 NPS-not-MBI (age 71.6 ± 8.8; 65.5% female) and 5078 No-NPS (age 71.2 ± 8.9; 67.6% female) participants. Compared with No-NPS, MBI participants had lower dementia-free survival (P < 0.0001) and 2.76-fold greater adjusted dementia incidence rate (95% CI: 2.27–3.35, P < 0.001); incidence rate in NPS-not-MBI did not differ from No-NPS (hazard ratio 0.97, 95% CI: 0.82–1.14, P = 0.687). Of those with MBI who progressed to dementia, 76.0% developed Alzheimer's disease. Similarly, in the SCD subsample (n = 3485), persons with MBI had 1.99-fold greater dementia incidence versus No-NPS (95% CI: 1.46–2.71, P < 0.001) while NPS-not-MBI did not differ from No-NPS (hazard ratio 0.92, 95% CI: 0.70–1.19, P = 0.511).

Incorporating natural history into assessment of psychiatric symptoms in accordance with MBI criteria enhances dementia prognostication and modelling.

Links between personality disorders and antisocial outcomes has not examined individual personality disorders, and the contribution of comorbidities remain uncertain. Previous systematic reviews are dated.

To synthesise evidence from observational studies on the risk of antisocial outcomes and recidivism associated with personality disorders.

We searched six bibliographic databases (up to March 2024) for observational studies examining the risk of antisocial behaviour, interpersonal violence and recidivism in individuals diagnosed with personality disorders, compared to controls. We explored sources of heterogeneity using subgroup analyses and meta-regression.

We identified 21 studies involving 83 418 individuals with personality disorders from 10 countries examining antisocial and violent outcomes (Aim 1), and 39 studies of 14 131 individuals from 13 countries with recidivism (or repeat offending) as the outcome (Aim 2). We found increased risks of violence among individuals with any personality disorder (odds ratio 4.5, 95% CI 3.0–6.7), particularly antisocial personality disorder (odds ratio 7.6, 95% CI 5.1–11.5) and borderline personality disorder (odds ratio 2.6, 95% CI 1.8–3.9). Individuals with any personality disorder (odds ratio 2.3, 95% CI 2.0–2.6) and antisocial personality disorder (odds ratio 2.8, 95% CI 1.6–4.9) also demonstrated an elevated risk of recidivism. Personality disorder types and comorbid substance use disorder were associated with between-study heterogeneity.

The assessment and management of personality disorders should be considered as part of violence prevention strategies. Improving identification and treatment of comorbid substance misuse may reduce adverse outcomes in individuals with personality disorders.

The prenatal and early-life periods pose a crucial neurodevelopmental window whereby disruptions to the intestinal microbiota and the developing brain may have adverse impacts. As antibiotics affect the human intestinal microbiome, it follows that early-life antibiotic exposure may be associated with later-life psychiatric or neurocognitive outcomes.

To explore the association between early-life (in utero and early childhood (age 0–2 years)) antibiotic exposure and the subsequent risk of psychiatric and neurocognitive outcomes.

A search was conducted using Medline, PsychINFO and Excerpta Medica databases on 20 November 2023. Risk of bias was assessed using the Newcastle-Ottawa scale, and certainty was assessed using the grading of recommendations, assessment, development and evaluation (GRADE) certainty assessment.

Thirty studies were included (n = 7 047 853 participants). Associations were observed between in utero antibiotic exposure and later development of autism spectrum disorder (ASD) (odds ratio 1.09, 95% CI: 1.02–1.16) and attention-deficit hyperactivity disorder (ADHD) (odds ratio 1.19, 95% CI: 1.11–1.27) and early-childhood exposure and later development of ASD (odds ratio 1.19, 95% CI: 1.01–1.40), ADHD (odds ratio 1.33, 95% CI: 1.20–1.48) and major depressive disorder (MDD) (odds ratio 1.29, 95% CI: 1.04–1.60). However, studies that used sibling control groups showed no significant association between early-life exposure and ASD or ADHD. No studies in MDD used sibling controls. Using the GRADE certainty assessment, all meta-analyses but one were rated very low certainty, largely owing to methodological and statistical heterogeneity.

While there was weak evidence for associations between antibiotic use in early-life and later neurodevelopmental outcomes, these were attenuated in sibling-controlled subgroup analyses. Thus, associations may be explained by genetic and familial confounding, and studies failing to utilise sibling-control groups must be interpreted with caution. PROSPERO ID: CRD42022304128

Clozapine therapy presents a risk of agranulocytosis, necessitating monitoring of white blood cell count. The detection of benign ethnic neutropenia (BEN), in which neutropenia can be present without an increased risk of infection, is particularly important in preventing unnecessary withdrawal of clozapine. BEN is strongly linked to the CC homozygote of the single nucleotide polymorphism rs2814778 in the atypical chemokine receptor-1 (ACKR1) gene.

We introduced voluntary genetic testing for BEN in one of our clozapine clinics, with the aim of assessing the prevalence of undiagnosed BEN in patients on clozapine.

We offered genetic testing for BEN to patients undergoing medium- and long-term clozapine treatment, and conducted a comparative analysis of neutrophil counts across three identified groups: those previously diagnosed with BEN, those with newly discovered BEN and those confirmed by genetic testing not to have BEN.

We conducted genetic testing for BEN on 108 patients. Of these, 16 were already registered as having BEN and had the CC homozygote. A further 26 patients (24% of the cohort) who were previously not diagnosed with BEN by standard haematological monitoring were found to have the CC homozygote on genetic testing. Unadjusted mean neutrophil counts were lowest for those with previously diagnosed BEN (2.5 × 109/L, 95% CI 2.2–2.8; P < 0.001 v. other groups), but those with newly discovered BEN had mean counts that were significantly lower (4.1 × 109/L, 95% CI 3.6–4.7) than those with TT and CT genotypes (5.1 × 109/L, 95% CI 4.7–5.4; P = 0.006).

Undiagnosed BEN was common in our naturalistic cohort. The integration of genetic testing into standard monitoring would enhance the management of clozapine therapy, potentially allowing for the safe reintroduction or continuation of clozapine in patients with hitherto unrecognised BEN. All current and prospective clozapine patients should be genetically tested for BEN.

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.