Prominent clinical perspectives posit that the interface of autism and (borderline) personality disorder manifests as either a misdiagnosis of the former as the latter or a comorbidity of both. In this editorial, we integrate these disparate viewpoints by arguing that personality difficulties are inherent to the autistic spectrum.

Despite strong evidence of efficacy of electroconvulsive therapy (ECT) in the treatment of depression, no sensitive and specific predictors of ECT response have been identified. Previous meta-analyses have suggested some pre-treatment associations with response at a population level.

Using 10 years (2009–2018) of routinely collected Scottish data of people with moderate to severe depression (n = 2074) receiving ECT we tested two hypotheses: (a) that there were significant group-level associations between post-ECT clinical outcomes and pre-ECT clinical variables and (b) that it was possible to develop a method for predicting illness remission for individual patients using machine learning.

Data were analysed on a group level using descriptive statistics and association analyses as well as using individual patient prediction with machine learning methodologies, including cross-validation.

ECT is highly effective for moderate to severe depression, with a response rate of 73% and remission rate of 51%. ECT response is associated with older age, psychotic symptoms, necessity for urgent intervention, severe distress, psychomotor retardation, previous good response, lack of medication resistance, and consent status. Remission has the same associations except for necessity for urgent intervention and, in addition, history of recurrent depression and low suicide risk. It is possible to predict remission with ECT with an accuracy of 61%.

Pre-ECT clinical variables are associated with both response and remission and can help predict individual response to ECT. This predictive tool could inform shared decision-making, prevent the unnecessary use of ECT when it is unlikely to be beneficial and ensure prompt use of ECT when it is likely to be effective.

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.

Evidence linking air pollutants and the risk of schizophrenia remains limited and inconsistent, and no studies have investigated the joint effect of air pollutant exposure and genetic factors on schizophrenia risk.

To investigate how exposure to air pollution affects schizophrenia risk and the potential effect modification of genetic susceptibility.

Our study was conducted using data on 485 288 participants from the UK Biobank. Cox proportional hazards models were used to estimate the schizophrenia risk as a function of long-term air pollution exposure presented as a time-varying variable. We also derived the schizophrenia polygenic risk score (PRS) utilising data provided by the UK Biobank, and investigated the modification effect of genetic susceptibility.

During a median follow-up period of 11.9 years, 417 individuals developed schizophrenia (mean age 55.57 years, s.d. = 8.68; 45.6% female). Significant correlations were observed between long-term exposure to four air pollutants (PM2.5; PM10; nitrogen oxides, NOx; nitrogen dioxide, NO2) and the schizophrenia risk in each genetic risk group. Interactions between genetic factors and the pollutants NO2 and NOx had an effect on schizophrenia events. Compared with those with low PRS and low air pollution, participants with high PRS and high air pollution had the highest risk of incident schizophrenia (PM2.5: hazard ratio = 6.25 (95% CI 5.03–7.76); PM10: hazard ratio = 7.38 (95% CI 5.86–9.29); NO2: hazard ratio = 6.31 (95% CI 5.02–7.93); NOx: hazard ratio = 6.62 (95% CI 5.24–8.37)).

Long-term exposure to air pollutants was positively related to the schizophrenia risk. Furthermore, high genetic susceptibility could increase the effect of NO2 and NOx on schizophrenia risk.

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.

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.