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.

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.

Working memory deficit, a key feature of schizophrenia, is a heritable trait shared with unaffected siblings. It can be attributed to dysregulation in transitions from one brain state to another.

Using network control theory, we evaluate if defective brain state transitions underlie working memory deficits in schizophrenia.

We examined average and modal controllability of the brain's functional connectome in 161 patients with schizophrenia, 37 unaffected siblings and 96 healthy controls during a two-back task. We use one-way analysis of variance to detect the regions with group differences, and correlated aberrant controllability to task performance and clinical characteristics. Regions affected in both unaffected siblings and patients were selected for gene and functional annotation analysis.

Both average and modal controllability during the two-back task are reduced in patients compared to healthy controls and siblings, indicating a disruption in both proximal and distal state transitions. Among patients, reduced average controllability was prominent in auditory, visual and sensorimotor networks. Reduced modal controllability was prominent in default mode, frontoparietal and salience networks. Lower modal controllability in the affected networks correlated with worse task performance and higher antipsychotic dose in schizophrenia (uncorrected). Both siblings and patients had reduced average controllability in the paracentral lobule and Rolandic operculum. Subsequent out-of-sample gene analysis revealed that these two regions had preferential expression of genes relevant to bioenergetic pathways (calmodulin binding and insulin secretion).

Aberrant control of brain state transitions during task execution marks working memory deficits in patients and their siblings.

Despite the high prevalence of social and performance anxiety, current treatments do not meet the full needs of patients. Development of novel anxiolytics with rapid onset of action for on-demand treatment of social and performance anxiety is an active area of clinical research.

To examine the anxiolytic effect of VQW-765, an α7-nAChR agonist, in subjects with performance anxiety.

We conducted a randomised, double-blind, placebo-controlled trial of 230 adults with a history of public speaking anxiety. Participants were randomly assigned to receive a single oral dose of 10 mg VQW-765 (n = 116) or placebo (n = 114), followed by a Trier Social Stress Test (TSST). Anxiety levels were assessed by the Subjective Units of Distress Scale (SUDS). Heart rate was monitored during the TSST. Plasma concentration of VQW-765 was measured after the TSST.

Subjects receiving VQW-765 showed a trend of improvement in intensity of anxiety, as measured by the SUDS, during the performance phase of a TSST compared with placebo (P = 0.1443). Females showed a larger magnitude and significant response to VQW-765 (P = 0.034). The pharmacokinetic/pharmacodynamic analysis observed an inverted U-shaped exposure–response relationship. Subjects in the middle 50% quantiles of VQW-765 plasma concentration showed significant improvement in the SUDS rating compared with placebo (P = 0.033); however, subgroup analysis revealed this was true only for females (P = 0.005). VQW-765 was safe and well tolerated.

This is the first study showing anxiolytic effect of an α7-nAChR agonist in humans. VQW-765 is a promising candidate to be developed for on-demand treatment of social anxiety disorder.

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.