Trace amine-associated receptor 1 (TAAR1) agonists offer a new approach, but there is uncertainty regarding their effects, exact mechanism of action and potential role in treating psychosis.

To evaluate the available evidence on TAAR1 agonists in psychosis, using triangulation of the output of living systematic reviews (LSRs) of animal and human studies, and provide recommendations for future research prioritisation.

This study is part of GALENOS (Global Alliance for Living Evidence on aNxiety, depressiOn and pSychosis). In the triangulation process, a multidisciplinary group of experts, including those with lived experience, met and appraised the first co-produced living systematic reviews from GALENOS, on TAAR1 agonists.

The animal data suggested a potential antipsychotic effect, as TAAR1 agonists reduced locomotor activity induced by pro-psychotic drug treatment. Human studies showed few differences for ulotaront and ralmitaront compared with placebo in improving overall symptoms in adults with acute schizophrenia (four studies, n = 1291 participants, standardised mean difference (SMD) 0.15, 95% CI −0.05 to 0.34). Large placebo responses were seen in ulotaront phase three trials. Ralmitaront was less efficacious than risperidone (one study, n = 156 participants, SMD = −0.53, 95% CI −0.86 to −0.20). The side-effect profile of TAAR1 agonists was favourable compared with existing antipsychotics. Priorities for future studies included (a) using different animal models of psychosis with greater translational validity; (b) animal and human studies with wider outcomes including cognitive and affective symptoms and (c) mechanistic studies and investigations of other potential applications, such as adjunctive treatments and long-term outcomes. Recommendations for future iterations of the LSRs included (a) meta-analysis of individual human participant data, (b) including studies that used different methodologies and (c) assessing other disorders and symptoms.

This co-produced, international triangulation examined the available evidence and developed recommendations for future research and clinical applications for TAAR1 agonists in psychosis. Broader challenges included difficulties in assessing the risk of bias, reproducibility, translation and interpretability of animal models to clinical outcomes, and a lack of individual and clinical characteristics in the human data. The research will inform a separate, independent prioritisation process, led by lived experience experts, to prioritise directions for future research.

There is a paucity of data guiding treatment duration of oral vancomycin for Clostridiodes difficile infection (CDI) in patients requiring concomitant systemic antibiotics.

To evaluate prescribing practices of vancomycin for CDI in patients that required concurrent systemic antibiotics and to determine whether a prolonged duration of vancomycin (>14 days), compared to a standard duration (10–14 days), decreased CDI recurrence.

In this retrospective cohort study, we evaluated adult hospitalized patients with an initial episode of CDI who were treated with vancomycin and who received overlapping systemic antibiotics for >72 hours. Outcomes of interest included CDI recurrence and isolation of vancomycin-resistant Enterococcus (VRE).

Among the 218 patients included, 36% received a standard duration and 64% received a prolonged duration of treatment for a median of 13 days (11–14) and 20 days (16–26), respectively. Patients who received a prolonged duration had a longer median duration of systemic antibiotic overlap with vancomycin (11 vs 8 days; P < .001) and significantly more carbapenem use and infectious disease consultation. Recurrence at 8 weeks (12% standard duration vs 8% prolonged duration; P = .367), recurrence at 6 months (15% standard duration vs 10% prolonged duration; P = .240), and VRE isolation (3% standard duration vs 9% prolonged duration; P = .083) were not significantly different between groups. Discontinuation of vancomycin prior to completion of antibiotics was an independent predictor of 8-week recurrence on multivariable logistic regression (OR, 4.8; 95% CI, 1.3–18.1).

Oral vancomycin prescribing relative to the systemic antibiotic end date may affect CDI recurrence to a greater extent than total vancomycin duration alone. Further studies are needed to confirm these findings.

Childhood trauma may impact the course of schizophrenia spectrum disorders (SSD), specifically in relation to the increased severity of depressive or negative symptoms. The type and impact of trauma may differ between sexes. In a large sample of recent-onset patients, we investigated the associations of depressive and negative symptoms with childhood trauma and whether these are sex-specific.

A total of 187 first-episode psychosis patients in remission (Handling Antipsychotic Medication: Long-term Evaluation of Targeted Treatment study) and 115 recent-onset SSD patients (Simvastatin study) were included in this cross-sectional study (men: n = 218; women: n = 84). Total trauma score and trauma subtypes were assessed using the Childhood Trauma Questionnaire Short Form; depressive and negative symptoms were rated using the Positive And Negative Symptoms Scale. Sex-specific regression analyses were performed.

Women reported higher rates of sexual abuse than men (23.5% v. 7.8%). Depressive symptoms were associated with total trauma scores and emotional abuse ratings in men (β: 0.219–0.295; p ≤ 0.001). In women, depressive symptoms were associated with sexual abuse ratings (β: 0.271; p = 0.011). Negative symptoms were associated with total trauma score and emotional neglect ratings in men (β: 0.166–0.232; p ≤ 0.001). Negative symptoms in women were not linked to childhood trauma, potentially due to lack of statistical power.

Depressive symptom severity was associated with different types of trauma in men and women with recent-onset SSD. Specifically, in women, depressive symptom severity was associated with childhood sexual abuse, which was reported three times as often as in men. Our results emphasize the importance of sex-specific analyses in SSD research.

PREDICT was a Canadian, multicenter, prospective, observational study in adults naïve to onabotulinumtoxinA treatment for chronic migraine (CM). We descriptively assess health resource utilization, work productivity, and acute medication use.

OnabotulinumtoxinA (155–195 U) was administered every 12 weeks over 2 years (≤7 treatment cycles). Participants completed a 4-item health resource utilization questionnaire and 6-item Work Productivity and Activity Impairment Questionnaire: Specific Health Problem V2.0. Acute medication use was recorded in daily headache diaries. Treatment-emergent adverse events were recorded throughout the study.

A total of 197 participants were enrolled, and 184 received ≥1 treatment with onabotulinumtoxinA and were included in the analysis. Between baseline and the final visit, there were decreases in the percentage of participants who reported headache-related healthcare professional visit(s) (96.2% to 76.8%) and those who received headache-related diagnostic testing (37.5% to 9.9%). Reductions from baseline were also observed in the mean number of headache-related visits to an emergency room/urgent care clinic (2.5 to 1.4) and median headache-related hospital admissions (4.0 to 1.0). OnabotulinumtoxinA improved work productivity and reduced the mean (standard deviation) number of hours missed from work over a 7-day period (6.1 [9.7] to 3.0 [6.8]). Mean (standard deviation) acute medication use decreased from baseline (15.2 [7.6] to 9.1 [6.5] days). No new safety signals were identified.

Real-world evidence from PREDICT demonstrates that onabotulinumtoxinA treatment for CM in the Canadian population reduces health resource utilization and acute medication use and improves workplace productivity, supporting the long-term benefits of using onabotulinumtoxinA for CM.

To scale-out an experiential teaching kitchen in Parks and Recreation centres’ after-school programming in a large urban setting among predominantly low-income, minority children.

We evaluated the implementation of a skills-based, experiential teaching kitchen to gauge programme success. Effectiveness outcomes included pre–post measures of child-reported cooking self-efficacy, attitudes towards cooking, fruit and vegetable preference, intention to eat fruits and vegetables and willingness to try new fruits and vegetables. Process outcomes included attendance (i.e., intervention dose delivered), cost, fidelity and adaptations to the intervention.

After-school programming in Parks and Recreation Community centres in Nashville, TN.

Predominantly low-income minority children aged 6–14 years.

Of the twenty-five city community centres, twenty-one successfully implemented the programme, and nineteen of twenty-five implemented seven or more of the eight planned sessions. Among children with pre–post data (n 369), mean age was 8·8 (sd 1·9) years, and 53·7 % were female. All five effectiveness measures significantly improved (P < 0·001). Attendance at sessions ranged from 36·3 % of children not attending any sessions to 36·6 % of children attending at least four sessions. Across all centres, fidelity was 97·5 %. The average food cost per serving was $1·37.

This type of nutritional education and skills building experiential teaching kitchen can be successfully implemented in a community setting with high fidelity, effectiveness and organisational alignment, while also expanding reach to low-income, underserved children.

Cognitive deficits may be characteristic for only a subgroup of first-episode psychosis (FEP) and the link with clinical and functional outcomes is less profound than previously thought. This study aimed to identify cognitive subgroups in a large sample of FEP using a clustering approach with healthy controls as a reference group, subsequently linking cognitive subgroups to clinical and functional outcomes.

204 FEP patients were included. Hierarchical cluster analysis was performed using baseline brief assessment of cognition in schizophrenia (BACS). Cognitive subgroups were compared to 40 controls and linked to longitudinal clinical and functional outcomes (PANSS, GAF, self-reported WHODAS 2.0) up to 12-month follow-up.

Three distinct cognitive clusters emerged: relative to controls, we found one cluster with preserved cognition (n = 76), one moderately impaired cluster (n = 74) and one severely impaired cluster (n = 54). Patients with severely impaired cognition had more severe clinical symptoms at baseline, 6- and 12-month follow-up as compared to patients with preserved cognition. General functioning (GAF) in the severely impaired cluster was significantly lower than in those with preserved cognition at baseline and showed trend-level effects at 6- and 12-month follow-up. No significant differences in self-reported functional outcome (WHODAS 2.0) were present.

Current results demonstrate the existence of three distinct cognitive subgroups, corresponding with clinical outcome at baseline, 6- and 12-month follow-up. Importantly, the cognitively preserved subgroup was larger than the severely impaired group. Early identification of discrete cognitive profiles can offer valuable information about the clinical outcome but may not be relevant in predicting self-reported functional outcomes.

Clinicians routinely use impressions of speech as an element of mental status examination. In schizophrenia-spectrum disorders, descriptions of speech are used to assess the severity of psychotic symptoms. In the current study, we assessed the diagnostic value of acoustic speech parameters in schizophrenia-spectrum disorders, as well as its value in recognizing positive and negative symptoms.

Speech was obtained from 142 patients with a schizophrenia-spectrum disorder and 142 matched controls during a semi-structured interview on neutral topics. Patients were categorized as having predominantly positive or negative symptoms using the Positive and Negative Syndrome Scale (PANSS). Acoustic parameters were extracted with OpenSMILE, employing the extended Geneva Acoustic Minimalistic Parameter Set, which includes standardized analyses of pitch (F0), speech quality and pauses. Speech parameters were fed into a random forest algorithm with leave-ten-out cross-validation to assess their value for a schizophrenia-spectrum diagnosis, and PANSS subtype recognition.

The machine-learning speech classifier attained an accuracy of 86.2% in classifying patients with a schizophrenia-spectrum disorder and controls on speech parameters alone. Patients with predominantly positive v. negative symptoms could be classified with an accuracy of 74.2%.

Our results show that automatically extracted speech parameters can be used to accurately classify patients with a schizophrenia-spectrum disorder and healthy controls, as well as differentiate between patients with predominantly positive v. negatives symptoms. Thus, the field of speech technology has provided a standardized, powerful tool that has high potential for clinical applications in diagnosis and differentiation, given its ease of comparison and replication across samples.

The PREDICT study assessed real-world, long-term health-related quality of life in adults with chronic migraine (CM) receiving onabotulinumtoxinA.

Canadian, multicenter, prospective, observational study in adults naïve to onabotulinumtoxinA for CM. OnabotulinumtoxinA (155–195 U) was administered every 12 weeks over 2 years (≤7 treatment cycles). Primary endpoint: mean change in Migraine-Specific Quality of Life Questionnaire (MSQ) at treatment 4 (Tx4) versus baseline. Secondary endpoints: mean change in MSQ at final visit versus baseline, and headache days.

184 participants (average age 45 years; 84.8% female; 94.6% Caucasian) received ≥1 onabotulinumtoxinA treatment; 150 participants completed 4 treatments (1 year) and 123 completed all 7 treatment cycles (2 years). Mean (SD) onabotulinumtoxinA dose per treatment cycle was 171 (18) U and treatment interval was 13.2 (1.8) weeks. Baseline mean (SD) 20.9 (6.7) headache days/month decreased (Tx1: −3.5 [6.3]; Tx4: −6.5 [6.6]; p < 0.0001 versus baseline). Mean (SD) increased from baseline in MSQ at Tx4 (restrictive: 21.5 [24.3], preventive: 19.5 [24.7], emotional: 22.9 [32.9]) and the final visit (restrictive: 21.3 [23.0], preventive: 19.2 [23.7], emotional: 27.4 [30.7]), exceeding minimal important differences (all p < 0.0001). Seventy-seven (41.8%) participants reported 168 treatment-emergent adverse events (TEAEs); 38 TEAEs (12.0%) were considered treatment-related. Four (2.2%) participants reported six serious TEAEs; none were considered treatment-related. No new safety signals were identified.

Real-world evidence from PREDICT demonstrates that onabotulinumtoxinA for CM in Canada improved MSQ scores and reduced headache frequency and severity, adding to the body of evidence on the long-term safety and effectiveness of onabotulinumtoxinA for CM.

Childhood trauma increases risk for psychopathology and cognitive impairment. Prior research mainly focused on the hippocampus and amygdala in single diagnostic categories. However, other brain regions may be impacted by trauma as well, and effects may be independent of diagnosis. This cross-sectional study investigated cortical and subcortical gray matter volume in relation to childhood trauma severity.

We included 554 participants: 250 bipolar-I patients, 84 schizophrenia-spectrum patients and 220 healthy individuals without a psychiatric history. Participants filled in the Childhood Trauma Questionnaire. Anatomical T1 MRI scans were acquired at 3T, regional brain morphology was assessed using Freesurfer.

In the total sample, trauma-related gray matter reductions were found in the frontal lobe (β = −0.049, p = 0.008; q = 0.048), this effect was driven by the right medial orbitofrontal, paracentral, superior frontal regions and the left precentral region. No trauma-related volume reductions were observed in any other (sub)cortical lobes nor the hippocampus or amygdala, trauma-by-group (i.e. both patient groups and healthy subjects) interaction effects were absent. A categorical approach confirmed a pattern of more pronounced frontal gray matter reductions in individuals reporting multiple forms of trauma and across quartiles of cumulative trauma scores. Similar dose−response patterns were revealed within the bipolar and healthy subgroups, but did not reach significance in schizophrenia-spectrum patients.

Findings show that childhood trauma is linked to frontal gray matter reductions, independent of psychiatric morbidity. Our results indicate that childhood trauma importantly contributes to the neurobiological changes commonly observed across psychiatric disorders. Frontal volume alterations may underpin affective and cognitive disturbances observed in trauma-exposed individuals.

Cognition is commonly affected in brain disorders. Non-invasive brain stimulation (NIBS) may have procognitive effects, with high tolerability. This meta-analysis evaluates the efficacy of transcranial magnetic stimulation (TMS) and transcranial Direct Current Stimulation (tDCS) in improving cognition, in schizophrenia, depression, dementia, Parkinson's disease, stroke, traumatic brain injury, and multiple sclerosis.

A PRISMA systematic search was conducted for randomized controlled trials. Hedges' g was used to quantify effect sizes (ES) for changes in cognition after TMS/tDCS v. sham. As different cognitive functions may have unequal susceptibility to TMS/tDCS, we separately evaluated the effects on: attention/vigilance, working memory, executive functioning, processing speed, verbal fluency, verbal learning, and social cognition.

We included 82 studies (n = 2784). For working memory, both TMS (ES = 0.17, p = 0.015) and tDCS (ES = 0.17, p = 0.021) showed small but significant effects. Age positively moderated the effect of TMS. TDCS was superior to sham for attention/vigilance (ES = 0.20, p = 0.020). These significant effects did not differ across the type of brain disorder. Results were not significant for the other five cognitive domains.

Our results revealed that both TMS and tDCS elicit a small trans-diagnostic effect on working memory, tDCS also improved attention/vigilance across diagnoses. Effects on the other domains were not significant. Observed ES were small, yet even slight cognitive improvements may facilitate daily functioning. While NIBS can be a well-tolerated treatment, its effects appear domain specific and should be applied only for realistic indications (i.e. to induce a small improvement in working memory or attention).

Although immune-mediated inflammatory diseases (IMID) are associated with multiple mental health conditions, there is a paucity of literature assessing personality disorders (PDs) in these populations. We aimed to estimate and compare the incidence of any PD in IMID and matched cohorts over time, and identify sociodemographic characteristics associated with the incidence of PD.

We used population-based administrative data from Manitoba, Canada to identify persons with incident inflammatory bowel disease (IBD), multiple sclerosis (MS) and rheumatoid arthritis (RA) using validated case definitions. Unaffected controls were matched 5:1 on sex, age and region of residence. PDs were identified using hospitalisation or physician claims. We used unadjusted and covariate-adjusted negative binomial regression to compare the incidence of PDs between the IMID and matched cohorts.

We identified 19 572 incident cases of IMID (IBD n = 6,119, MS n = 3,514, RA n = 10 206) and 97 727 matches overall. After covariate adjustment, the IMID cohort had an increased incidence of PDs (incidence rate ratio [IRR] 1.72; 95%CI: 1.47–2.01) as compared to the matched cohort, which remained consistent over time. The incidence of PDs was similarly elevated in IBD (IRR 2.19; 95%CI: 1.69–2.84), MS (IRR 1.79; 95%CI: 1.29–2.50) and RA (IRR 1.61; 95%CI: 1.29–1.99). Lower socioeconomic status and urban residence were associated with an increased incidence of PDs, whereas mid to older adulthood (age 45–64) was associated with overall decreased incidence. In a restricted sample with 5 years of data before and after IMID diagnosis, the incidence of PDs was also elevated before IMID diagnosis among all IMID groups relative to matched controls.

IMID are associated with an increased incidence of PDs both before and after an IMID diagnosis. These results support the relevance of shared risk factors in the co-occurrence of PDs and IMID conditions.