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.

The ability to communicate is integral to all human relationships. Previous research has specifically highlighted communication within families as both a risk and protective factor for anxiety disorders and/or depression. Yet, there is limited understanding about whether communication is amenable to intervention in the context of adolescent psychopathology, and whether doing so improves outcomes.

The aim of this systematic review was to determine in which contexts and for whom does addressing communication in families appear to work, not work and why?

We pre-registered our systematic review with PROSPERO (identifier CRD42022298719), followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidance and assessed study quality with the Risk of Bias 2 tool.

Seven randomised controlled trials were identified from a systematic search of the literature. There was significant heterogeneity in the features of communication that were measured across these studies. There were mixed findings regarding whether family-focused interventions led to improvements in communication. Although there was limited evidence that family-focused interventions led to improvements in communication relative to interventions without a family-focused component, we discuss these findings in the context of the significant limitations in the studies reviewed.

We conclude that further research is required to assess the efficacy of family-focused interventions for improving communication in the context of anxiety and depression in those aged 14–24 years.

The clinical course of psychotic disorders is highly variable. Typically, researchers have captured different course types using broad pre-defined categories. However, whether these adequately capture symptom trajectories of psychotic disorders has not been fully assessed. Using data from AESOP-10, we sought to identify classes of individuals with specific symptom trajectories over a 10-year follow-up using a data-driven approach.

AESOP-10 is a follow-up, at 10 years, of 532 incident cases with a first episode of psychosis initially identified in south-east London and Nottingham, UK. Using extensive information on fluctuations in the presence of psychotic symptoms, we fitted growth mixture models to identify latent trajectory classes that accounted for heterogeneity in the patterns of change in psychotic symptoms over time.

We had sufficient data on psychotic symptoms during the follow-up on 326 incident patients. A four-class quadratic growth mixture model identified four trajectories of psychotic symptoms: (1) remitting-improving (58.5%); (2) late decline (5.6%); (3) late improvement (5.4%); (4) persistent (30.6%). A persistent trajectory, compared with remitting-improving, was associated with gender (more men), black Caribbean ethnicity, low baseline education and high disadvantage, low premorbid IQ, a baseline diagnosis of non-affective psychosis and long DUP. Numbers were small, but there were indications that those with a late decline trajectory more closely resembled those with a persistent trajectory.

Our current approach to categorising the course of psychotic disorders may misclassify patients. This may confound efforts to elucidate the predictors of long-term course and related biomarkers.

To determine the baseline individual characteristics that predicted symptom recovery and functional recovery at 10-years following the first episode of psychosis.

AESOP-10 is a 10-year follow up of an epidemiological, naturalistic population-based cohort of individuals recruited at the time of their first episode of psychosis in two areas in the UK (South East London and Nottingham). Detailed information on demographic, clinical, and social factors was examined to identify which factors predicted symptom and functional remission and recovery over 10-year follow-up. The study included 557 individuals with a first episode psychosis. The main study outcomes were symptom recovery and functional recovery at 10-year follow-up.

At 10 years, 46.2% (n = 140 of 303) of patients achieved symptom recovery and 40.9% (n = 117) achieved functional recovery. The strongest predictor of symptom recovery at 10 years was symptom remission at 12 weeks (adj OR 4.47; CI 2.60–7.67); followed by a diagnosis of depression with psychotic symptoms (adj OR 2.68; CI 1.02–7.05). Symptom remission at 12 weeks was also a strong predictor of functional recovery at 10 years (adj OR 2.75; CI 1.23–6.11), together with being from Nottingham study centre (adj OR 3.23; CI 1.25–8.30) and having a diagnosis of mania (adj OR 8.17; CI 1.61–41.42).

Symptom remission at 12 weeks is an important predictor of both symptom and functional recovery at 10 years, with implications for illness management. The concepts of clinical and functional recovery overlap but should be considered separately.

Neuropsychological investigations can help untangle the aetiological and phenomenological heterogeneity of schizophrenia but have scarcely been employed in the context of treatment-resistant (TR) schizophrenia. No population-based study has examined neuropsychological function in the first-episode of TR psychosis.

We report baseline neuropsychological findings from a longitudinal, population-based study of first-episode psychosis, which followed up cases from index admission to 10 years. At the 10-year follow up patients were classified as treatment responsive or TR after reconstructing their entire case histories. Of 145 cases with neuropsychological data at baseline, 113 were classified as treatment responsive, and 32 as TR at the 10-year follow-up.

Compared with 257 community controls, both case groups showed baseline deficits in three composite neuropsychological scores, derived from principal component analysis: verbal intelligence and fluency, visuospatial ability and executive function, and verbal memory and learning (p values⩽0.001). Compared with treatment responders, TR cases showed deficits in verbal intelligence and fluency, both in the extended psychosis sample (t = −2.32; p = 0.022) and in the schizophrenia diagnostic subgroup (t = −2.49; p = 0.017). Similar relative deficits in the TR cases emerged in sub-/sensitivity analyses excluding patients with delayed-onset treatment resistance (p values<0.01–0.001) and those born outside the UK (p values<0.05).

Verbal intelligence and fluency are impaired in patients with TR psychosis compared with those who respond to treatment. This differential is already detectable – at a group level – at the first illness episode, supporting the conceptualisation of TR psychosis as a severe, pathogenically distinct variant, embedded in aberrant neurodevelopmental processes.

The incidence of psychotic disorders is elevated in some minority ethnic populations. However, we know little about the outcome of psychoses in these populations.

To investigate patterns and determinants of long-term course and outcome of psychoses by ethnic group following a first episode.

ÆSOP-10 is a 10-year follow-up of an ethnically diverse cohort of 532 individuals with first-episode psychosis identified in the UK. Information was collected, at baseline, on clinical presentation and neurodevelopmental and social factors and, at follow-up, on course and outcome.

There was evidence that, compared with White British, Black Caribbean patients experienced worse clinical, social and service use outcomes and Black African patients experienced worse social and service use outcomes. There was evidence that baseline social disadvantage contributed to these disparities.

These findings suggest ethnic disparities in the incidence of psychoses extend, for some groups, to worse outcomes in multiple domains.