A youth mental health crisis is considered one of the great challenges of our time, and research and clinical services in child and adolescent psychiatry have become a priority for governments and funders. Academic leadership is needed to drive forward research. It is not clear how many senior academic leadership posts (professorships) there are in child and adolescent psychiatry, nor how this benchmarks against a similarly sized medical specialty.

This study aimed to determine the number of professorships in child and adolescent psychiatry in the UK and Ireland compared to a similarly sized specialty. A secondary aim was to identify the number of clinical trials registered for mental and behavioural disorders in children.

We identified registered specialists in child and adolescent psychiatry and a similarly sized specialty who held full professorships in medical schools. We searched the International Standard Randomised Controlled Trial Number (ISRCTN) and ClinicalTrials.gov for trials.

As of 23 March 2023, there were 1725 doctors on the General Medical Council's (GMC) specialist register in child and adolescent psychiatry. The closest specialty in terms of number of registered specialists was neurology (N = 1724). We identified 24 professors in child and adolescent psychiatry across the UK and Ireland, compared to 124 in neurology. For every intervention trial registered for mental and behavioural disorders in children, there were approximately ten trials registered for diseases of the nervous system.

Despite equivalent numbers of medical specialists in child and adolescent psychiatry and neurology, there is a striking disparity in the number of professorship appointments. While young peoples’ mental health has, ostensibly, become a priority for policy-makers and funders, this is not reflected in medical professorship appointments. The paucity of senior academic child and adolescent psychiatrists has real-world implications for training, research, innovation and service development in mental health services.

Anxiety symptoms are elevated among people with joint hypermobility. The underlying neural mechanisms are attributed theoretically to effects of variant connective tissue on the precision of interoceptive representations contributing to emotions.

To investigate the neural correlates of anxiety and hypermobility using functional neuroimaging.

We used functional magnetic resonance neuroimaging to quantify regional brain responses to emotional stimuli (facial expressions) in people with generalised anxiety disorder (GAD) (N = 30) and a non-anxious comparison group (N = 33). All participants were assessed for joint laxity and were classified (using Brighton Criteria) for the presence and absence of hypermobility syndrome (HMS: now considered hypermobility spectrum disorder).

Participants with HMS showed attenuated neural reactivity to emotional faces in specific frontal (inferior frontal gyrus, pre-supplementary motor area), midline (anterior mid and posterior cingulate cortices) and parietal (precuneus and supramarginal gyrus) regions. Notably, interaction between HMS and anxiety was expressed in reactivity of the left amygdala (a region implicated in threat processing) and mid insula (primary interoceptive cortex) where activity was amplified in people with HMS with GAD. Severity of hypermobility in anxious, compared with non-anxious, individuals correlated with activity within the anterior insula (implicated as the neural substrate linking anxious feelings to physiological state). Amygdala-precuneus functional connectivity was stronger in participants with HMS, compared with non-HMS participants.

The predisposition to anxiety in people with variant connective tissue reflects dynamic interactions between neural centres processing threat (amygdala) and representing bodily state (insular and parietal cortices). Correspondingly, interventions to regulate amygdala reactivity while enhancing interoceptive precision may have therapeutic benefit for symptomatic hypermobile individuals.

Reliable and specific biomarkers that can distinguish autism spectrum disorders (ASDs) from commonly co-occurring attention-deficit/hyperactivity disorder (ADHD) are lacking, causing misses and delays in diagnosis, and reducing access to interventions and quality of life.

To examine whether an innovative, brief (1-min), videogame method called Computerised Assessment of Motor Imitation (CAMI), can identify ASD-specific imitation differences compared with neurotypical children and children with ADHD.

This cross-sectional study used CAMI alongside standardised parent-report (Social Responsiveness Scale, Second Edition) and observational measures of autism (Autism Diagnostic Observation Schedule-Second Edition; ADOS-2), ADHD (Conners) and motor ability (Physical and Neurological Examination for Soft Signs). The sample comprised 183 children aged 7–13 years, with ADHD (without ASD), with ASD (with and without ADHD) and who were neurotypical.

Regardless of co-occurring ADHD, children with ASD showed poorer CAMI performance than neurotypical children (P < 0.0001; adjusted R2 = 0.28), whereas children with ADHD and neurotypical children showed similar CAMI performance. Receiver operating curve and support vector machine analyses showed that CAMI distinguishes ASD from both neurotypical children (80% true positive rate) and children with ADHD (70% true positive rate), with a high success rate significantly above chance. Among children with ASD, poor CAMI performance was associated with increased autism traits, particularly ADOS-2 measures of social affect and restricted and repetitive behaviours (adjusted R2 = 0.23), but not with ADHD traits or motor ability.

Four levels of analyses confirm that poor imitation measured by the low-cost and scalable CAMI method specifically distinguishes ASD not only from neurotypical development, but also from commonly co-occurring ADHD.

Nearly 3% of adults have attention-deficit and hyperactivity disorder (ADHD), although in the UK, most are undiagnosed. Adults with ADHD on average experience poorer educational and employment outcomes, worse physical and mental health and are more likely to die prematurely. No studies have yet used mortality data to examine the life expectancy deficit experienced by adults with diagnosed ADHD in the UK or worldwide.

This study used the life-table method to calculate the life-expectancy deficit for people with diagnosed ADHD using data from UK primary care.

A matched cohort study using prospectively collected primary care data (792 general practices, 9 561 450 people contributing eligible person-time from 2000–2019). We identified 30 039 people aged 18+ with diagnosed ADHD, plus a comparison group of 300 390 participants matched (1:10) by age, sex and primary care practice. We used Poisson regression to estimate age-specific mortality rates, and life tables to estimate life expectancy for people aged 18+ with diagnosed ADHD.

Around 0.32% of adults in the cohort had an ADHD diagnosis, ~1 in 9 of all adults with ADHD. Diagnoses of common physical and mental health conditions were more common in adults with diagnosed ADHD than the comparison group. The apparent reduction in life expectancy for adults with diagnosed ADHD relative to the general population was 6.78 years (95% CI: 4.50 to 9.11) for males, and 8.64 years (95% CI: 6.55 to 10.91) for females.

Adults with diagnosed ADHD are living shorter lives than they should. We believe that this is likely caused by modifiable risk factors and unmet support and treatment needs in terms of both ADHD and co-occurring mental and physical health conditions. This study included data from adults with diagnosed ADHD; the results may not generalise to the entire population of adults with ADHD, the vast majority of whom are undiagnosed.

Depressive and anxiety disorders constitute a major component of the disease burden of mental disorders in China.

To comprehensively evaluate the disease burden of depressive and anxiety disorders in China.

The raw data is sourced from the Global Burden of Disease, Injuries, and Risk Factors Study (GBD) 2021. This study presented the disease burden by prevalence and disability-adjusted life years (DALYs) of depressive and anxiety disorders at both the national and provincial levels in China from 1990 to 2021, and by gender (referred to as 'sex' in the GBD 2021) and age.

From 1990 to 2021, the number of depressive disorder cases (from 34.4 to 53.1 million) and anxiety disorders (from 40.5 to 53.1 million) increased by 54% (95% uncertainty intervals: 43.9, 65.3) and 31.2% (19.9, 43.8), respectively. The age-standardised prevalence rate of depressive disorders decreased by 6.4% (2.9, 10.4), from 3071.8 to 2875.7 per 100 000 persons, while the prevalence of anxiety disorders remained stable. COVID-19 had a significant adverse impact on both conditions. There was considerable variability in the disease burden across genders, age groups, provinces and temporal trends. DALYs showed similar patterns.

The burden of depressive and anxiety disorders in China has been rising over the past three decades, with a larger increase during COVID-19. There is notable variability in disease burden across genders, age groups and provinces, which are important factors for the government and policymakers when developing intervention strategies. Additionally, the government and health authorities should consider the potential impact of public health emergencies on the burden of depressive and anxiety disorders in future efforts.

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.

Intergenerational transmission of mental disorders has been well established, but it is unclear whether exposure to a child's mental disorder increases parents' subsequent risk of mental disorders.

We examined the association of mental disorders in children with their parents' subsequent mental disorders.

In this population-based cohort study, we included all individuals with children born in Finland or Denmark in 1990–2010. Information about mental disorders was acquired from national registers. The follow-up period began when the parent's eldest child was 5 years old (for ICD-10 codes F10–F60) or 1 year old (for codes F70–F98) and ended on 31 December 2019 or when the parent received a mental disorder diagnosis, died, or emigrated from Finland or Denmark. The associations of mental disorders in children with their parents' subsequent mental disorders were examined using Cox proportional hazards models.

The study cohort included 1 651 723 parents. In total, 248 328 women and 250 763 men had at least one child who had been diagnosed with a mental disorder. The risk of a parent receiving a mental disorder diagnosis was higher among those who had a child with a mental disorder compared with those who did not. For both parents, the hazard ratios were greatest in the first 6 months after the child's diagnosis (hazard ratio 2.04–2.54), followed by a subtle decline in the risk (after 2 years, the hazard ratio was 1.33–1.77).

Mental disorders in children are associated with a greater risk of subsequent mental disorders among their parents. Additional support is needed for parents whose children have been recently diagnosed with a mental disorder.

Depressive disorders pose a significant global public health challenge, yet evidence on their burden remains insufficient.

To report the global, regional and national burden of depressive disorders and their attributable risk factors from 1990 to 2021.

Data from the Global Burden of Disease 2021 were analyzed for 204 countries and territories from 1990 to 2021. We explored the age-standardised incidence, prevalence and disability-adjusted life years (DALYs) of depressive disorders by age, gender and sociodemographic index.

In 2021, there were 357.44 million incident cases, 332.41 million prevalent cases and 56.33 million DALYs. Age-standardised rates for incidence, prevalence and DALYs were 4333.62, 4006.82 and 681.14 per 100 000 persons, with annual declines of 0.06%, 0.03% and 0.04%. Uganda, Greenland and Lesotho had the highest prevalence, while Spain, Mexico and Uruguay showed the largest increases. Greenland and Brunei Darussalam had the highest and lowest age-standardised DALYs rates, respectively. DALYs peaked in the 55–59 age group for men and 60–64 for women, with higher rates in women. Regionally, a U-shaped association was found between the sociodemographic index and DALYs rates. Population growth was the main driver for the increase in DALYs cases. Childhood maltreatment was the leading risk factor, with intimate partner violence affecting more females and childhood sexual abuse more males.

Despite decreasing trends in incidence, prevalence and DALYs rates, absolute case numbers and age-standardised rates continue to increase for depressive disorders. Tackling childhood abuse and improving depressive disorder management are crucial to reducing future burdens.

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.

Accurate diagnosis of bipolar disorder (BPD) is difficult in clinical practice, with an average delay between symptom onset and diagnosis of about 7 years. A depressive episode often precedes the first manic episode, making it difficult to distinguish BPD from unipolar major depressive disorder (MDD).

We use genome-wide association analyses (GWAS) to identify differential genetic factors and to develop predictors based on polygenic risk scores (PRS) that may aid early differential diagnosis.

Based on individual genotypes from case–control cohorts of BPD and MDD shared through the Psychiatric Genomics Consortium, we compile case–case–control cohorts, applying a careful quality control procedure. In a resulting cohort of 51 149 individuals (15 532 BPD patients, 12 920 MDD patients and 22 697 controls), we perform a variety of GWAS and PRS analyses.

Although our GWAS is not well powered to identify genome-wide significant loci, we find significant chip heritability and demonstrate the ability of the resulting PRS to distinguish BPD from MDD, including BPD cases with depressive onset (BPD-D). We replicate our PRS findings in an independent Danish cohort (iPSYCH 2015, N = 25 966). We observe strong genetic correlation between our case–case GWAS and that of case–control BPD.

We find that MDD and BPD, including BPD-D are genetically distinct. Our findings support that controls, MDD and BPD patients primarily lie on a continuum of genetic risk. Future studies with larger and richer samples will likely yield a better understanding of these findings and enable the development of better genetic predictors distinguishing BPD and, importantly, BPD-D from MDD.

Women with schizophrenia frequently discontinue antipsychotic medications during pregnancy. However, evidence on the risk of postpartum relapse associated with antipsychotic use during pregnancy is lacking.

To investigate the within-individual association between antipsychotic continuation during pregnancy and postpartum relapse in women with schizophrenia.

This retrospective cohort study used data of women with schizophrenia who gave live birth between 2007 and 2018 identified from the National Health Information Database of South Korea. Women were classified according to antipsychotic use patterns during the 12 months before delivery as non-users, discontinuers and continuers. Relapse was defined as admission for psychosis (ICD-10, F20–29). The incidence rate ratio (IRR) for admission for psychosis in the 6-month postpartum period was estimated using conditional Poisson regression, with the reference period set between 2 and 1 years before delivery. Additionally, we calculated the relative risk ratios (RRRs) for the IRRs of different antipsychotic use patterns.

Among the 3026 women included in the analysis (median age 34 years, interquartile range 31–37), the within-individual risk of admission for psychosis in the 6-month postpartum period was 0.56 times (RRR, 95% CI 0.36–0.87) lower in continuers (IRR = 1.31, 95% CI 0.89–1.72) than in discontinuers (IRR = 2.34, 95% CI 1.87–2.91). Among discontinuers, the IRRs of admission for psychosis in the 6-month postpartum period did not change significantly with the timing of discontinuation (trend P = 0.946).

Antipsychotic continuation during pregnancy was associated with a reduced risk of postpartum relapse in women with schizophrenia. Continuing antipsychotics during pregnancy would be recommended after a risk–benefit assessment.

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.

Negative perceptions of mental health professionals can deter individuals from seeking mental healthcare. Given the high burden of mental health globally, it is essential to understand attitudes towards mental health professionals. Social media platforms like Twitter/X provide valuable insights into the views of the general population.

This study aimed to use social media to investigate the (a) public perceptions (positive or negative) of mental health professionals, (b) changes in these perceptions over time and (c) engagement levels with tweets about mental health professionals over time.

We collected all tweets posted in English between 2007 and 2023, containing key terms such as ‘mental health’, ‘psychology’, ‘psychologist’, ‘psychiatry’, ‘psychiatrist’, ‘neurology’ and ‘neurologist’. A total of 1500 tweets were manually classified into categories, which were used in conjunction with semi-supervised machine learning to categorise a large data-set.

For most key terms, there was a higher frequency of positive perceptions compared with negative, with this trend improving over time. However, tweets containing ‘psychiatrist’ exhibited a higher proportion of negative perceptions (n = 4872, 39.52% negative v. n = 1972, 15.99% positive before 2020). After 2020, the gap narrowed, yet negative perceptions continued to dominate (n = 5505, 36.10% negative v. n = 3472, 22.77% positive).

Overall, positive perceptions of mental health and mental health professionals increased over time. However, ‘psychiatrist’ had a consistently higher proportion of negative perceptions. This study underscores the need to improve public perception of psychiatrists, and demonstrates the potential of using Twitter/X to better understand public attitudes and reduce stigma associated with accessing mental health services.

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.

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.

Previous economic evidence about interventions for schizophrenia is outdated, non-transparent and/or limited to a specific clinical context.

We developed a de novo discrete event simulation (DES) model for estimating the cost-effectiveness of interventions in schizophrenia in the UK.

The DES model was developed based on the structure of previous models, populated with demographic, clinical and cost data from the UK, and antipsychotics' effects from recent network meta-analyses. We simulated treatment pathways for patients with first-episode schizophrenia including events such as relapse, remission, treatment discontinuation, cardiovascular disease and death and estimated costs (2020£) taking the National Health Service perspective and quality-adjusted life years (QALYs) over ten years. Using the model, we ranked ten first-line antipsychotics based on their QALYs and cost-effectiveness.

Amisulpride was associated with the highest QALYs, followed by risperidone long-acting injection (LAI), aripiprazole-LAI (6.121, 6.084, 6.070, respectively) and others (5.947–6.058). The most cost-effective antipsychotics were amisulpride, olanzapine and risperidone-LAI, with total probability of rankings of 1, ≤2, ≤3, that is, 95%, 89%, 80%, respectively; meanwhile, the least cost-effective were cariprazine, lurasidone and quetiapine, with total probability of rankings of 10, ≥9, ≥8, that is, 96%, 92%, 81%, respectively. Results were robust across sensitivity analyses and influenced primarily by relapse relevant parameters.

Our findings suggest amisulpride (or risperidone-LAI where oral treatment is inappropriate) as the best overall first-line option based on QALYs and cost-effectiveness. Our ranking may be used to guide decision-making between antipsychotics. Our model is open source and could be applied to the other settings.

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.