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.

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.

Clozapine-induced inflammation, such as myocarditis and pneumonia, can occur during initial titration and can be fatal. Fever is often the first sign of severe inflammation, and early detection and prevention are essential. Few studies have investigated the effects of clozapine titration speed and concomitant medication use on the risk of clozapine-induced inflammation.

We evaluated the risk factors for clozapine-associated fever, including titration speed, concomitant medication use, gender and obesity, and their impact on the risk of fever and the fever onset date.

We conducted a case-control study. The medical records of 539 Japanese participants with treatment-resistant schizophrenia at 21 hospitals in Japan who received clozapine for the first time between 2010 and 2022 were retrospectively investigated. Of these, 512 individuals were included in the analysis. Individuals were divided into three groups according to the titration rate recommended by international guidelines for East Asians: the faster titration group, the slower titration group and the ultra-slower titration group. The use of concomitant medications (such as antipsychotics, mood stabilisers, hypnotics and anxiolytics) at clozapine initiation was comprehensively investigated. Logistic regression analysis was performed to identify the explanatory variables for the risk of a fever of 37.5°C or higher lasting at least 2 days.

Fever risk significantly increased with faster titration, male gender and concomitant use of valproic acid or quetiapine. No increased fever risk was detected with the use of other concomitant drugs, such as olanzapine, lithium or orexin receptor antagonists. Fever onset occurred significantly earlier with faster titration. Multivariate analysis identified obesity as being a factor that accelerated fever onset.

A faster titration speed and concomitant treatment with valproic acid and quetiapine at clozapine initiation increased the risk of clozapine-associated fever. Clinicians should titrate clozapine with caution and consider both the titration speed and concomitant medications.

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

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

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

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

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