Within the medical model, ‘impairment’ is required for a diagnosis of autism. However, the diagnostic manuals provide limited guidance as to how to interpret impairment, which can impact diagnostic rates and the provision of support. Impairment is discussed within the context of the medical model and current sociocultural landscape.

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.

Evidence is largely limited regarding the extent to which abnormal behavioural profiles, including physical inactivity, sedentary behaviour and inadequate sleep duration, impact long-term health conditions in individuals with pre-existing depression.

To investigate the associations between accelerometer-derived daily movement behaviours and mortality in individuals with pre-existing depression.

Between 2013 and 2015, a total of 10 914 individuals with pre-existing depression were identified from the UK Biobank through multiple sources including self-reported symptoms, records of antidepressant usage and diagnostic recording based on the 10th Revision of the International Classification of Diseases (ICD-10) codes F32–F33. These participants were subsequently followed up until 2021. Wrist-worn accelerometers were used for objective measurement of sleep duration, sedentary behaviour, moderate-to-vigorous physical activity (MVPA) and light physical activity (LPA) over a span of seven consecutive days.

During a median follow-up of 6.9 years, 434 deaths occurred among individuals with pre-existing depression. We observed a U-shaped association between sleep duration and mortality in individuals with pre-existing depression, with the lowest risk occurring at approximately 9 h/day. Both MVPA and LPA exhibited an L-shaped pattern in relation to mortality, indicating that engaging in higher levels of physical activity was associated with lower risk of mortality in individuals with pre-existing depression, but the beneficial effect reached a plateau after 50 min/day for MVPA and 350 min/day for LPA. We found a positive association between sedentary time and mortality, and the risk apparently increased above 8 h/day. Moreover, substituting 1 hour/day of sedentary time with LPA or MVPA was significantly associated with a 12% (hazard ratio: 0.88, 95% CI: 0.83–0.94) and 24% (hazard ratio: 0.76, 95% CI: 0.61–0.94) lower risk of mortality, respectively.

Our study found the beneficial effect of adequate sleep duration, high levels of physical activity and short sedentary time on risk of mortality among individuals with pre-existing depression.

Knowledge is growing on the essential role of neural circuits involved in aberrant cognitive control and reward sensitivity for the onset and maintenance of binge eating.

To investigate how the brain's reward (bottom-up) and inhibition control (top-down) systems potentially and dynamically interact to contribute to subclinical binge eating.

Functional magnetic resonance imaging data were acquired from 30 binge eaters and 29 controls while participants performed a food reward Go/NoGo task. Dynamic causal modelling with the parametric empirical Bayes framework, a novel brain connectivity technique, was used to examine between-group differences in the directional influence between reward and executive control regions. We explored the proximal risk factors for binge eating and its neural basis, and assessed the predictive ability of neural indices on future disordered eating and body weight.

The binge eating group relative to controls displayed fewer reward-inhibition undirectional and directional synchronisations (i.e. medial orbitofrontal cortex [mOFC]–superior parietal gyrus [SPG] connectivity, mOFC → SPG excitatory connectivity) during food reward_nogo condition. Trait impulsivity is a key proximal factor that could weaken the mOFC–SPG connectivity and exacerbate binge eating. Crucially, this core mOFC–SPG connectivity successfully predicted binge eating frequency 6 months later.

These findings point to a particularly important role of the bottom-up interactions between cortical reward and frontoparietal control circuits in subclinical binge eating, which offers novel insights into the neural hierarchical mechanisms underlying problematic eating, and may have implications for the early identification of individuals suffering from strong binge eating-associated symptomatology in the general population.

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.

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.

Having a relapse of schizophrenia or recurrent psychosis is feared by patients, can cause social and personal disruption and has been suggested to cause long-term deterioration, possibly because of a toxic biological process.

To assess whether relapse affected the social and clinical outcomes of people enrolled in a 24-month randomised controlled trial of antipsychotic medication dose reduction versus maintenance treatment.

The trial involved participants with a diagnosis of schizophrenia or recurrent, non-affective psychosis. Relapse was defined as admission to hospital or significant deterioration (assessed by a blinded end-point committee). We analysed the relationship between relapse during the trial and social functioning, quality of life, symptom scores (Positive and Negative Syndrome Scale) and rates of being in employment, education or training at 24-month follow-up. We also analysed changes in these measures during the trial among those who relapsed and those who did not. Sensitivity analyses were conducted examining the effects of ‘severe’ relapse (i.e. admission to hospital).

During the course of the trial, 82 out of 253 participants relapsed. There was no evidence for a difference between those who relapsed and those who did not on changes in social functioning, quality of life, symptom scores or overall employment rates between baseline and 24-month follow-up. Those who relapsed showed no change in their social functioning or quality of life, and a slight improvement in symptoms compared to baseline. They were more likely than those who did not relapse to have had a change in their employment status (mostly moving out of employment, education or training), although numbers changing status were small. Sensitivity analyses showed the same results for those who experienced a ‘severe’ relapse.

Our data provide little evidence that relapse has a detrimental effect in the long term in people with schizophrenia and recurrent psychosis.