Although cognitive remediation (CR) improves cognition and functioning, the key features that promote or inhibit its effectiveness, especially between cognitive domains, remain unknown. Discovering these key features will help to develop CR for more impact.

To identify interrelations between cognition, symptoms, and functioning, using a novel network analysis approach and how CR affects these recovery outcomes.

A secondary analysis of randomized controlled trial data (N = 165) of CR in early psychosis. Regularized partial correlation networks were estimated, including symptoms, cognition, and functioning, for pre-, post-treatment, and change over time. Pre- and post-CR networks were compared on global strength, structure, edge invariance, and centrality invariance.

Cognition, negative, and positive symptoms were separable constructs, with symptoms showing independent relationships with cognition. Negative symptoms were central to the CR networks and most strongly associated with change in functioning. Verbal and visual learning improvement showed independent relationships to improved social functioning and negative symptoms. Only visual learning improvement was positively associated with personal goal achievement. Pre- and post-CR networks did not differ in structure (M = 0.20, p = 0.45) but differed in global strength, reflecting greater overall connectivity in the post-CR network (S = 0.91, p = 0.03).

Negative symptoms influenced network changes following therapy, and their reduction was linked to improvement in verbal and visual learning following CR. Independent relationships between visual and verbal learning and functioning suggest that they may be key intervention targets to enhance social and occupational functioning.

Adolescence is a critical developmental phase during which young people are vulnerable to the experiences of mental ill-health and social exclusion (consisting of various domains including education and employment, housing, finances and social supports and relationships). The aims of this study were to (i) obtain an understanding of the relationships between social exclusion, mental health and wellbeing of young people; and (ii) identify potentially modifiable targets, or population groups that require greater or targeted supports.

Data were obtained from the Mission Australia 2022 Youth Survey, Australia’s largest annual population-wide survey of young people aged 15–19 years (n = 18,800). Participants’ experiences of social exclusion in different domains were explored (e.g., prevalence, co-occurrence and controlling for differences in demographic characteristics). Multivariable linear regression models were used to map the relationships between social exclusion domains and mental health and wellbeing, controlling for confounding factors where necessary.

Sixty per cent of all young people experienced social exclusion in at least one domain, 25% in multiple. Young people who identified as gender diverse, Indigenous, living in a remote/rural or socio-economically disadvantaged area and with a culturally diverse background were more likely to report social exclusion. A strong association was seen between all domains of social exclusion and poor mental health (e.g., higher psychological distress and loneliness, reduced personal wellbeing, reduced sense of control over their life and a more negative outlook on the future). Notably, difficulties in socialising and obtaining social support were critical factors linked to increased psychological distress and reduced wellbeing.

Findings underscore the need to address multiple domains of social exclusion concurrently, and in collaboration with youth mental healthcare. Prevention efforts aimed at early identification and intervention should be prioritised to support young people vulnerable to social exclusion. Screening approaches are needed to identify individuals and groups of young people in need of support, and to facilitate care coordination across multiple providers.

Although atypical antipsychotics have lowered the prevalence and severity of extrapyramidal symptoms (EPS), they still contribute to the overall side-effect burden of approved antipsychotics. Drugs with novel mechanisms without D2 dopamine receptor blocking activity have shown promise in treating schizophrenia without the side effects of currently available treatments. KarXT (xanomeline–trospium chloride) represents a possible alternative that targets muscarinic receptors. KarXT demonstrated efficacy compared with placebo in 3 out of 3 short-term acute studies and has not been associated with many of the side effects of D2 dopamine receptor antagonists. Here, we further characterize EPS rates with KarXT in these trials.

EMERGENT-1 (NCT03697252), EMERGENT-2 (NCT04659161), and EMERGENT-3 (NCT04738123) were 5-week, randomized, double-blind, placebo-controlled, inpatient trials in people with schizophrenia experiencing acute psychosis. Data from the safety populations, defined as all participants who received ³1 dose of trial medication, were pooled. For this analysis, we used a broader definition of EPS-related adverse events (AEs) to encompass any new onset of dystonia, dyskinesia, akathisia, or extrapyramidal disorder reported any time after the first dose of medication. Additionally, EPS were assessed by examining change from baseline to week 5 on the Simpson-Angus Scale (SAS), Barnes Akathisia Rating Scale (BARS), and Abnormal Involuntary Movement Scale (AIMS).

A total of 683 participants (KarXT, n=340; placebo, n=343) were included in the analyses. The rate of treatment-emergent AEs (TEAEs) associated with EPS was 3.2% in the KarXT group vs 0.9% in the placebo group. The most commonly reported TEAE was akathisia (KarXT, 2.4%; placebo 0.9%); half of possible akathisia cases in the KarXT group (4/8 TEAEs) were from a single US site, considered by the investigator to be unrelated to trial drug, and resolved without treatment. Overall rates of akathisia TEAEs deemed related to trial drug were low (KarXT, 0.6%; placebo 0.3%). Dystonia, dyskinesia, and extrapyramidal disorder TEAEs were reported by only a single subject each (0.3%) in the KarXT arm. All reported TEAEs were mild to moderate in severity. KarXT was associated with no clinically meaningful mean±SD changes from baseline to week 5 on the SAS (-0.1±0.6), BARS (-0.1±0.9), or AIMS (0.0±0.7).

The incidence of EPS-related TEAEs with KarXT was low in comparison to those observed in similar trials of antipsychotics (D2 dopamine receptor antagonists), although head-to-head studies have not been completed. Moreover, KarXT was not associated with increased scores on EPS scales (SAS, BARS, AIMS) across 5 weeks of treatment. These results, combined with the robust efficacy of KarXT in trials to date, suggest that KarXT’s novel mechanism of action may provide therapeutic benefit in the absence of EPS frequently associated with currently available antipsychotics.

Karuna Therapeutics

Many patients with Fontan physiology are unable to achieve the minimum criteria for peak effort during cardiopulmonary exercise testing. The purpose of this study is to determine the influence of physical activity and other clinical predictors related to achieving peak exercise criteria, signified by respiratory exchange ratio ≥ 1.1 in youth with Fontan physiology.

Secondary analysis of a cross-sectional study of 8–18-year-olds with single ventricle post-Fontan palliation who underwent cardiopulmonary exercise testing (James cycle protocol) and completed a past-year physical activity survey. Bivariate associations were assessed by Wilcoxon rank-sum test and simple regression. Conditional inference forest algorithm was used to classify participants achieving respiratory exchange ratio > 1.1 and to predict peak respiratory exchange ratio.

Of the n = 43 participants, 65% were male, mean age was 14.0 ± 2.4 years, and 67.4% (n = 29) achieved respiratory exchange ratio ≥ 1.1. Despite some cardiopulmonary exercise stress test variables achieving statistical significance in bivariate associations with participants achieving respiratory exchange ratio > 1.1, the classification accuracy had area under the precision recall curve of 0.55. All variables together explained 21.4% of the variance in respiratory exchange ratio, with peak oxygen pulse being the most informative.

Demographic, physical activity, and cardiopulmonary exercise test measures could not classify meeting peak exercise criteria (respiratory exchange ratio ≥ 1.1) at a satisfactory accuracy. Correlations between respiratory exchange ratio and oxygen pulse suggest the augmentation of stroke volume with exercise may affect the Fontan patient’s ability to sustain high-intensity exercise.

Evidence suggests that cognitive subtypes exist in schizophrenia that may reflect different neurobiological trajectories. We aimed to identify whether IQ-derived cognitive subtypes are present in early-phase schizophrenia-spectrum disorder and examine their relationship with brain structure and markers of neuroinflammation.

161 patients with recent-onset schizophrenia spectrum disorder (<5 years) were recruited. Estimated premorbid and current IQ were calculated using the Wechsler Test of Adult Reading and a 4-subtest WAIS-III. Cognitive subtypes were identified with k-means clustering. Freesurfer was used to analyse 3.0 T MRI. Blood samples were analysed for hs-CRP, IL-1RA, IL-6 and TNF-α.

Three subtypes were identified indicating preserved (PIQ), deteriorated (DIQ) and compromised (CIQ) IQ. Absolute total brain volume was significantly smaller in CIQ compared to PIQ and DIQ, and intracranial volume was smaller in CIQ than PIQ (F(2, 124) = 6.407, p = 0.002) indicative of premorbid smaller brain size in the CIQ group. CIQ had higher levels of hs-CRP than PIQ (F(2, 131) = 5.01, p = 0.008). PIQ showed differentially impaired processing speed and verbal learning compared to IQ-matched healthy controls.

The findings add validity of a neurodevelopmental subtype of schizophrenia identified by comparing estimated premorbid and current IQ and characterised by smaller premorbid brain volume and higher measures of low-grade inflammation (CRP).

A disproportionate number of people with mental ill-health experience social exclusion. Appropriate measurement tools are required to progress opportunities to improve social inclusion. We have developed a novel measure, the Filia Social Inclusion Measure (F-SIM). Here we aimed to present a more concise, easy-to-use form, while retaining its measurement integrity by (i) refining the F-SIM using traditional and contemporary item-reduction techniques; and (ii) testing the psychometric properties of the reduced measure.

Five hundred and six participants completed the F-SIM, younger and older groups of people with serious mental illness (including psychosis, mood, anxiety disorders) and same-aged community counterparts. The F-SIM was completed at baseline and 2-week follow-up, alongside other measures (including social inclusion, loneliness). The F-SIM was refined using multidimensional scaling network analysis, confirmatory factor analysis and item response theory. The psychometric evaluation included assessment of dimensionality, internal consistency, test–retest reliability, discriminant ability and construct validity.

The F-SIM was reduced from 135-items to 16; with 4-items in each domain of housing and neighbourhood, finances, employment and education and social participation and relationships. Psychometric properties were sound, including strong internal consistency within domains (all α > 0.85) and excellent overall (α = 0.92). Test–retest reliability was also high (γ = 0.90). Differences between groups were observed; clinical subgroups consistently reported lower levels of social inclusion compared to community counterparts.

The F-SIM16 is a sound, reliable, brief self-report measure of social inclusion suitable for use in clinical and research settings. It has the potential to evaluate the effectiveness of interventions, and aid in fostering targeted and personalised needs-based care.

There is limited understanding of treatment pathways for paediatric sleep-disordered breathing. This study explored current UK pathways and what is important to well-being for parents and children.

The study comprised in-depth qualitative interviews (n = 22) with parents of children (2–9 years) with symptoms of sleep-disordered breathing referred to a regional ENT clinic (n = 11), general practitioners who might refer these children to ENT (n = 5) and hospital doctors involved in treating these children (n = 6). Interviews were audio recorded, transcribed verbatim, anonymised and analysed thematically.

General practitioners rarely identify seeing children with sleep-disordered breathing; conversely hospital doctors identify unsuspected issues. Parents are worried their child will stop breathing, but routes to referral and diagnosis are not straightforward. Modern technology can aid investigation and diagnosis. Patient weight is an issue for general practitioners and hospital doctors. Adenotonsillectomy is the treatment of choice, and information on paediatric sleep-disordered breathing is needed.

Guidelines for the management of paediatric sleep-disordered breathing are needed.