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In this study, we examined how four components of the therapeutic relationship—working alliance, real relationship, and positive and negative affective reactions of the patient toward their therapist—relate to each other and to the psychotherapy session outcome, from the patient’s point of view. Our simple comprised 700 adult patients in individual psychotherapy who were recruited and participated online. They underwent a baseline evaluation of their most recent therapy session, which encompassed a series of validated self-report measures focused on specific elements of the therapeutic relationship. The results revealed that, from the patient’s perspective, working alliance, real relationship, and positive affective reactions toward the therapist were positively correlated with session outcome, while negative affective reactions were negatively correlated. All components predicted session outcome when simultaneously included in a regression model. Collectively, these four components accounted for 30% of the variance in session outcome. Factor analysis revealed four distinct factors, underlying perceptions of the therapeutic relationship. Notably, the bond dimension of the alliance was sufficiently different from the task and goal dimensions, warranting consideration as a distinct construct. These findings, although cross-sectional, lay the groundwork for a more nuanced investigation of multiple dimensions of the therapeutic relationship.

Background There is a growing recognition of the key role of the therapeutic relationship in the outcomes of psychotherapy. However, current understanding of its specific components, their interplay and related patient-therapist dynamics is limited. Objective (a) To validate two self-report measures to assess subjective affective reactions of patients toward their psychotherapists during specific therapy sessions, and (b) to explore the relationships and dynamics among four elements of the therapeutic relationship: patient reactions toward the therapist, working alliance, alliance ruptures and repairs, and the real relationship. Methods This study uses a nonrandomized, two-time point longitudinal design. The target population is adult patients currently engaged in individual psychotherapy for heterogeneous mental conditions. Participants are recruited through two online recruitment platforms: Research for Me and ResearchMatch. Data collection involves administering two surveys through the Qualtrics online survey platform. The baseline survey assesses information about the most recent therapy session and the preceding week, while the follow-up survey collects data on the subsequent therapy session and the days leading up to it. Discussion This research offers three main contributions: (a) it furthers evidence-based assessment in psychotherapy by creating and validating two novel, succinct self-report tools; (b) it enhances theoretical understanding within therapeutic relationship research by exploring the significant impact of patients' perceptions of relationship elements on session outcomes variability; and (c) it will identify therapeutic relationship elements that can either enhance or hinder the overall relationship quality and session outcomes. Ethics and dissemination The study protocol was approved by the Institutional Review Board of the University of North Carolina at Chapel Hill. The results will be published in indexed peer-reviewed journals and presented at relevant psychology and psychiatry conferences.

Abstract Background Numerous interventions for irritability in autism spectrum disorder (ASD) have been investigated. We aimed to appraise the magnitude of pharmacological and non-pharmacological interventions for irritability in ASD without any restrictions in terms of eligible interventions. Methods We systematically searched PubMed/MEDLINE, Scopus, and Web of Science until April 15, 2023. We included randomized controlled trials (RCTs) with a parallel design that examined the efficacy of interventions for the treatment of irritability in patients of any age with ASD without any restrictions in terms of eligible interventions. We performed a random-effects meta-analysis by pooling effect sizes as Hedges’ g. We classified assessed interventions as follows: pharmacological monotherapy, risperidone plus adjuvant therapy versus risperidone monotherapy, non-pharmacological intervention, and dietary intervention. We utilized the Cochrane tool to evaluate the risk of bias in each study and the GRADE approach to assess the certainty of evidence for each meta-analyzed intervention. Results Out of 5640 references, we identified 60 eligible articles with 45 different kinds of interventions, including 3531 participants, of which 80.9% were males (mean age [SD] = 8.79 [3.85]). For pharmacological monotherapy, risperidone (Hedges’ g − 0.857, 95% CI − 1.263 to − 0.451, certainty of evidence: high) and aripiprazole (Hedges’ g − 0.559, 95% CI − 0.767 to − 0.351, certainty of evidence: high) outperformed placebo. Among the non-pharmacological interventions, parent training (Hedges’ g − 0.893, 95% CI − 1.184 to − 0.602, certainty of evidence: moderate) showed a significant result. None of the meta-analyzed interventions yielded significant effects among risperidone + adjuvant therapy and dietary supplementation. However, several novel molecules in augmentation to risperidone outperformed risperidone monotherapy, yet from one RCT each. Limitations First, various tools have been utilized to measure the irritability in ASD, which may contribute to the heterogeneity of the outcomes. Second, meta-analyses for each intervention included only a small number of studies and participants. Conclusions Only risperidone, aripiprazole among pharmacological interventions, and parent training among non-pharmacological interventions can be recommended for irritability in ASD. As an augmentation to risperidone, several novel treatments show promising effects, but further RCTs are needed to replicate findings. Trial registration PROSPERO, CRD42021243965.

Abstract Neurocognitive deficits are a core feature of psychotic disorders, but it is unclear whether they affect all individuals uniformly. The aim of this systematic review and meta-analysis was to synthesize the evidence on the magnitude, progression, and variability of neurocognitive functioning in individuals with first-episode psychosis (FEP). A multistep literature search was conducted in several databases up to November 1, 2022. Original studies reporting on neurocognitive functioning in FEP were included. The researchers extracted the data and clustered the neurocognitive tasks according to the seven Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) domains and six additional domains. Random-effect model meta-analyses, assessment of publication biases and study quality, and meta-regressions were conducted. The primary effect size reported was Hedges g of (1) neurocognitive functioning in individuals at FEP measuring differences with healthy control (HC) individuals or (2) evolution of neurocognitive impairment across study follow-up intervals. Of 30,384 studies screened, 54 were included, comprising 3,925 FEP individuals and 1,285 HC individuals. Variability analyses indicated greater variability in FEP compared to HC at baseline and follow-up. We found better neurocognitive performance in the HC group at baseline and follow-up but no differences in longitudinal neurocognitive changes between groups. Across the 13 domains, individuals with FEP showed improvement from baseline in all studied domains, except for visual memory. Metaregressions showed some differences in several of the studied domains. The findings suggest that individuals with FEP have marked cognitive impairment, but there is greater variability in cognitive functioning in patients than in HC. This suggests that subgroups of individuals suffer severe disease-related cognitive impairments, whereas others may be much less affected. While these impairments seem stable in the medium term, certain indicators may suggest potential further decline in the long term for a specific subgroup of individuals, although more research is needed to clarify this. Overall, this study highlights the need for tailored neurocognitive interventions for individuals with FEP based on their specific deficits and progression.

Background Sexually transmitted infections (STIs), along with sexual health and behaviour, have received little attention in schizophrenia patients. Aims To systematically review and meta-analytically characterise the prevalence of STIs and sexual risk behaviours among schizophrenia patients. Method Web of Science, PubMed, BIOSIS, KCI-Korean Journal Database, MEDLINE, Russian Science Citation Index, SciELO and Cochrane Central Register were systematically searched from inception to 6 July 2023. Studies reporting on the prevalence or odds ratio of any STI or any outcome related to sexual risk behaviours among schizophrenia samples were included. PRISMA/MOOSE-compliant (CRD42023443602) random-effects meta-analyses were used for the selected outcomes. Q-statistics, I2 index, sensitivity analyses and meta-regressions were used. Study quality and publication bias were assessed. Results Forty-eight studies (N = 2 459 456) reporting on STI prevalence (including 15 allowing for calculation of an odds ratio) and 33 studies (N = 4255) reporting on sexual risk behaviours were included. Schizophrenia samples showed a high prevalence of STIs and higher risks of HIV (odds ratio = 2.11; 95% CI 1.23–3.63), hepatitis C virus (HCV, odds ratio = 4.54; 95% CI 2.15–961) and hepatitis B virus (HBV; odds ratio = 2.42; 95% CI 1.95–3.01) infections than healthy controls. HIV prevalence was higher in Africa compared with other continents and in in-patient (rather than out-patient) settings. Finally, 37.7% (95% CI 31.5–44.4%) of patients were sexually active; 35.0% (95% CI 6.6–59.3%) reported consistent condom use, and 55.3% (95% CI 25.0–82.4%) maintained unprotected sexual relationships. Conclusions Schizophrenia patients have high prevalence of STIs, with several-fold increased risks of HIV, HBV and HCV infection compared with the general population. Sexual health must be considered as an integral component of care.

Background: The dynamics of global, state-dependent reconfigurations in brain connectivity are yet unclear. We aimed at assessing reconfigurations of the global signal correlation coefficient (GSCORR), a measure of the connectivity between each voxel timeseries and the global signal, from resting-state to a stop-signal task. The secondary aim was to assess the relationship between GSCORR and blood-oxygen-level-dependent (BOLD) activations or deactivation across three different trial-conditions (GO, STOP-correct, and STOP-incorrect). Methods: As primary analysis we computed whole-brain, voxel-wise GSCORR during resting-state (GSCORR-rest) and stop-signal task (GSCORR-task) in 107 healthy subjects aged 21–50, deriving GSCORR-shift as GSCORR-task minus GSCORR-rest. GSCORR-tr and trGSCORR-shift were also computed on the task residual time series to quantify the impact of the task-related activity during the trials. To test the secondary aim, brain regions were firstly divided in one cluster showing significant task-related activation and one showing significant deactivation across the three trial conditions. Then, correlations between GSCORR-rest/task/shift and activation/deactivation in the two clusters were computed. As sensitivity analysis, GSCORR-shift was computed on the same sample after performing a global signal regression and GSCORR-rest/task/shift were correlated with the task performance. Results: Sensory and temporo-parietal regions exhibited a negative GSCORR-shift. Conversely, associative regions (ie. left lingual gyrus, bilateral dorsal posterior cingulate gyrus, cerebellum areas, thalamus, posterolateral parietal cortex) displayed a positive GSCORR-shift (FDR-corrected p < 0.05). GSCORR-shift showed similar patterns to trGSCORR-shift (magnitude increased) and after global signal regression (magnitude decreased). Concerning BOLD changes, Brodmann area 6 and inferior parietal lobule showed activation, while posterior parietal lobule, cuneus, precuneus, middle frontal gyrus showed deactivation (FDR-corrected p < 0.05). No correlations were found between GSCORR-rest/task/shift and beta-coefficients in the activation cluster, although negative correlations were observed between GSCORR-task and GO/STOP-correct deactivation (Pearson rho=-0.299/-0.273; Bonferroni-p < 0.05). Weak associations between GSCORR and task performance were observed (uncorrected p < 0.05). Conclusion: GSCORR state-dependent reconfiguration indicates a reallocation of functional resources to associative areas during stop-signal task. GSCORR, activation and deactivation may represent distinct proxies of brain states with specific neurofunctional relevance.

BackgroundPsychotherapists need effective tools to monitor changes in the patient’s affective perception of the therapist and the therapeutic relationship during sessions to tailor therapeutic interventions and improve treatment outcomes. This study aims to evaluate the factor structure, reliability, and validity of the in-Session Patient Affective Reactions Questionnaire (SPARQ), a concise self-report measure designed for practical application in real-world psychotherapy settings.MethodsValidation data was gathered from (N = 700) adult patients in individual psychotherapy. These patients completed the SPARQ in conjunction with additional measures capturing sociodemographic details, characteristics of therapeutic interventions, individual personality traits, mental health symptom severity, elements of the therapeutic relationship, and session outcomes. This comprehensive approach was employed to assess the construct and criterion-related validity of the SPARQ.ResultsThe SPARQ has a two-factor structure: Positive Affect (k = 4, ω total = .87) and Negative Affect (k = 4, ω total = .75). Bifactor confirmatory factor analysis (CFA) yielded the following fit indices: X2[df] = 2.53, CFI = .99; TLI = .98; RMSEA = .05; and SRMR = .02. Multi-group CFAs demonstrated measurement invariance (i) across patients who attended psychotherapy sessions in person versus in remote mode, and (ii) across patients with and without psychiatric diagnoses confirmed metric invariance. Furthermore, the SPARQ showed meaningful correlations with concurrently administered measures.DiscussionThe SPARQ proves to be a valuable instrument in clinical, training, and research contexts, adept at capturing patients’ session-level affective responses towards their therapist and perceptions of the therapeutic alliance. Comprehensive descriptive statistics and a range of score precision indices have been reported, intended to serve as benchmarks for future research.

Background: The effectiveness of long-acting injectable (LAI) antipsychotics in preventing relapses of first-episode psychosis is currently debated. Objectives: The study aimed to investigate the number of psychiatric hospitalizations comparing the LAI cohort versus the oral cohort during different phases of the illness, pre-LAI treatment, during LAI treatment, and after LAI treatment. Design: A naturalistic study was conducted on two independent cohorts of early psychosis patients receiving treatment from a specific early intervention service. The first cohort comprised 228 patients who received LAIs, while the second cohort comprised 667 patients who had never received LAIs. Methods: This study was designed as a longitudinal observational study conducted within a naturalistic clinical setting in two cohorts of early psychosis patients. Repeated series ANCOVA (ANCOVA-r) was used to study the number of hospitalizations in the different study periods (T1 = from the date of the first psychiatric record to the beginning of the mirror period; T2 = the mirror period; T3 = from the LAI implementation to the LAI discontinuation; and T4 = from the LAI discontinuation to the end). In all cases, discontinuation of LAI involved the return to oral treatment. In all, 35 patients had not T4 as they were still on LAI treatment at the time of database closing (September 2020), and their data were not included in the analysis of the effect of the LAI discontinuation. Results: The patients in the LAI cohort were younger, more frequently males, presented more schizophrenia diagnoses, and had a higher number of hospitalizations (2.50 ± 2.61 versus 1.19 ± 1.69; p

BackgroundThe quality of the therapeutic relationship is pivotal in determining psychotherapy outcomes. However, facilitating patients’ self-awareness, reflection on, and sharing of their affective responses toward their therapist remains underexplored as a potential tool for enhancing this relationship and subsequent treatment outcomes. ObjectiveThe primary objective of this study is to examine whether and how the patients’ regular self-monitoring and self-reflection (fostered by the systematic compilation of a brief postsession battery) on their affective reactions toward the psychotherapist impact the quality of the therapeutic relationship and treatment outcomes in individual psychotherapy. Secondary objectives are to (1) explore whether and how the characteristics of the patient, the therapist, and the process moderate the effect of regular self-monitoring on the therapeutic relationship and outcomes; (2) examine the relationships between the affective response of the patient, the alliance, and the result of the therapy session outcome; and (3) explore how the affective responses of the patient unfold or change throughout the course of the therapy. MethodsWe conducted a 1:1 randomized controlled trial of adults in individual psychotherapy versus individual psychotherapy plus self-monitoring. Participants will be enrolled through the web-based recruitment platforms “ResearchMatch” and “Research for Me,” and data will be collected through web-based surveys. Participants in the control group will receive only their regular individual psychotherapy (treatment as usual) and will not complete postsession questionnaires. Participants in the intervention group will continue their regular individual psychotherapy sessions and complete the “in-Session Patient Affective Reactions Questionnaire” and the “Rift In-Session Questionnaire” following each therapy session in the 10 weeks of the trial. Additionally, after completion of the postsession battery, they will receive general written feedback encouraging them to discuss their feelings and reflections with their therapist. Participants in both groups will complete a comprehensive psychological assessment at baseline, midtrial (week 5), and end-of-trial (week 10). The primary outcome measure of the trial is the “Clinical Outcomes in Routine Evaluation-Outcome Measure,” while the secondary outcomes are the “Real Relationship Inventory-Client-Short Form,” the “Working Alliance Inventory-Short Revised,” and the number of scheduled therapy sessions that the patient has missed or canceled. ResultsThe trial was approved by the institutional review board of the University of North Carolina at Chapel Hill. Recruitment started in September 2023. A total of 475 individuals completed the baseline assessment. Data collection was completed in February 2024. The results are expected to be published in the autumn of 2024. ConclusionsThis study could reveal key information on how regular self-monitoring and introspection can influence both the therapeutic relationship and treatment outcomes. Findings have the potential to shape interventions, enhance the efficacy of psychotherapeutic sessions, and possibly offer a cost-effective strategy for improving patients’ well-being. Trial RegistrationClinicalTrials.gov NCT06038747; https://classic.clinicaltrials.gov/ct2/show/NCT06038747 International Registered Report Identifier (IRRID)DERR1-10.2196/55369

Background: Depression is a condition which affects the individuals’ entire existence. The difficulty in emotionally tuning in to the environment and the resulting sensation of loneliness have frequently been described as salient points of depressive experience. To our knowledge there are no studies that phenomenologically analyze how depressed people feel perceived by others. Methods: Aiming to fill this gap, this study builds on a previous work, which carried out a literature screening and a thematic analysis on the subjective experience of depression. The narratives collected in this way were analyzed using a bottom-up qualitative method (Consensual Quality Research). Results: Four main categories of experience related to perceived social apprehension of depression have been identified: (1) feeling guilty about not meeting others' expectations, (2) feeling socially misunderstood, (3) bringing to light an inconvenient truth that others do not want to see, and (4) hiding from exposure to the judgement of others. Limitations: A broader and more specific data collection on the topic is missing. Conclusions: Depressed patients often feel misunderstood by their social environment, which belittles or dramatizes their condition or doesn't realize how otherwise normal requests can instead cost a lot of effort, generating feelings of guilt and inability. This frequently pushes depressed individuals to try to hide their condition by isolating themselves or wearing a social mask. The difficulty in emotional attunement already present in depression can only worsen in the face of this feeling of incomprehension, generating a vicious circle of non-recognition that ends up maintaining the depressive state.

The present study reports on the development and validation of the clinician affective response (CARE) scale. The CARE scale was designed as a self-report measure of therapists’ patterns of thoughts, feelings, and behaviors toward the patient during an individual psychotherapy session. An initial pool of 116 items was generated, and its quality was evaluated by subject matter experts. Validation data were gathered from licensed psychotherapists (n=554). We used exploratory factor analysis and item response theory-graded response modeling to select items, confirmatory factor analysis to test how well the factor structure fit the data, and k-fold cross-validation to ascertain the robustness of the model. Criterion validity was evaluated by correlating the scores of the scale with the characteristics of therapists, patients, and treatment. The selected model consists of 15 items and a 3-factor structure, which showed excellent model fit, good internal consistency, and evidence of criterion validity. The CARE scale, short and quick to complete, enables therapists to reflect on and recognize their inner experiences and quantify these experiences in ways conducive to statistical analysis and research. Furthermore, the monitoring of these affective reactions toward their patients can guide therapeutic interventions and inform clinical supervisors.

Under standard care, psychotic disorders can have limited response to treatments, high rates of chronicity and disability, negative impacts on families, and wider social and economic costs. In an effort to improve early detection and care of individuals developing a psychotic illness, early intervention in psychosis services and early detection services have been set up in various countries since the 1980s. In April 2016, NHS England implemented a new ‘access and waiting times’ standard for early intervention in psychosis to extend the prevention of psychosis across England. Unfortunately, early intervention and early detection services are still not uniformly distributed in the UK, leaving gaps in service provision. The aim of this paper is to provide a business case model that can guide clinicians and services looking to set up or expand early detection services in their area. The paper also focuses on some existing models of care within the Pan-London Network for Psychosis Prevention teams.

Objective: To provide a review of journal articles discussing clinical cases or vignettes of psychoanalysis or psychoanalytic psychotherapy of patients affected by bipolar disorder. Methods: A thorough search of journal articles was performed in five databases to identify studies published from 1990-2021. Results: Twenty-four articles were included in this review, comprising a total of 29 case reports. The most common theoretical approach adopted by the authors was “object relations.” Two main sets of clinical-theoretical considerations and recommendations emerge: the applicability of analytic treatment to patients with bipolar disorder – taking into account their analyzability and practical arrangements for conducting therapy – and theoretical speculations on the nature and development of the illness, as well as on the conceptualization of its different phases. Conclusion: Our findings reveal that there is some psychoanalytic literature providing insight into the psychological dynamics and treatment of patients with bipolar disorder. Elaboration of this literature may help improve our understanding and provide more accurate and comprehensive descriptions of the intrapsychic and interpersonal dynamics of these patients, yielding potentially valuable information for clinical and research purposes, particularly with regard to reducing interpersonal conflict, and increasing insight and engagement with lifestyle changes and other behaviors likely to promote health and stability.

Background: Discontinuation of treatment in people with first episode psychosis (FEP) is common, but the extent to which this is related to specific adverse effects of antipsychotic medications is unclear. Objectives: To investigate whether antipsychotic discontinuation is associated with the prescription of particular antipsychotics and particular adverse effects. Design: Retrospective cohort study. Methods: We assembled de-identified electronic health record (EHR) data from 2309 adults with FEP who received care from the South London and Maudsley NHS Foundation Trust between 1st April 2008 and 31st March 2019. Associations between antipsychotic medications, clinician-recorded side effects and treatment discontinuation were investigated across a mean follow-up period of 34.2 months using Cox regression. Results: The mean age of patients was 26.7 years and 1492 (64.6%) were male. Among first prescribed antipsychotic medications, discontinuation occurred earlier with haloperidol [hazard ratio (HR) = 2.78, 95% CI = 1.69–4.60] and quetiapine (HR = 1.43, 95% CI = 1.16–1.80) than with olanzapine. Discontinuation occurred sooner when there was evidence of extrapyramidal symptoms (HR = 1.33, 95% CI = 1.08–1.64) or sexual dysfunction (HR = 1.59, 95% CI = 1.03–2.46). Among antipsychotics prescribed at any point during treatment, lurasidone (HR = 1.40, 95% CI = 1.10–1.78) and aripiprazole (HR = 1.09, 95% CI = 1.01–1.19) were associated with earlier discontinuation than olanzapine. Conversely, clozapine (HR = 0.55, 95% CI = 0.41–0.73) and paliperidone 1-monthly (PP1M) long-acting injectable (HR = 0.80, 95% CI = 0.68–0.94) were associated with later discontinuation. Unexpectedly, for antipsychotics prescribed at any stage of treatment, sedation (HR = 0.89, 95% CI = 0.81–0.97), weight gain (HR = 0.73, 95% CI = 0.64–0.83), and multiple side effects (HR = 0.83, 95% CI = 0.76–0.90) were associated with later discontinuation. Conclusion: Earlier treatment discontinuation associated with sexual or extrapyramidal side effects could be related to their rapid onset and poor tolerability. Later treatment discontinuation associated with clozapine and PP1M could be related to the relative efficacy of these treatments. These findings merit consideration when selecting antipsychotic therapy for people with FEP.

Abstract Background Once psychosis has set in, it is difficult for patients to achieve full recovery. Prevention of psychosis and early intervention are promising for improving the outcomes of this disorder. In the last two decades, neurocognition has been studied as a biomarker for clinical-high risk for psychosis (CHR-P). However, neurocognitive functioning has been under-investigated in adolescents. Methods We enrolled 116 adolescents from 12 to 17 years old (mean = 15.27, SD = 1.56; 76 females). This 3-year cohort study aimed to identify differences in neurocognitive and overall functioning in three groups of adolescent patients divided according to the semi-structured interview Comprehensive Assessment of At-Risk Mental States (CAARMS): adolescents with established psychosis, adolescents with CHR-P, and adolescents not meeting either criteria (non-CHR-P). To differentiate the profiles, clinicians administered cognitive evaluation and neuropsychological tasks. Moreover, they filled in scales to assess their global, social, and role functioning and a questionnaire to assess the severity of the disease. Results We made a between-group comparison on neurocognitive measures and found that the CHR-P and the psychosis groups differed in processing speed (TMT-A; p = .002 in BVN categorial fluency (p = .018), and Rey–Osterrieth complex figure drawing from memory task (p = .014), with psychosis group showing worse performance. No differences emerged between non-CHR-P and CHR-P (p = .014) individuals. CHR-P had better functioning than the psychosis group but worse than the non-CHR-P one. Conclusions These results confirm that neurocognition can be a helpful biomarker in identifying specific subgroups of adolescents with emerging psychopathology and help clinicians develop stratified preventive approaches.

Psychosis is a psychopathological syndrome that can be triggered or caused by exposure to high altitude (HA). Psychosis can occur alone as isolated HA psychosis or can be associated with other mental and often also somatic symptoms as a feature of delirium. Psychosis can also occur as a symptom of high altitude cerebral edema (HACE), a life-threatening condition. It is unclear how psychotic symptoms at HA should be classified into existing diagnostic categories of the most widely used classification systems of mental disorders, including the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) and the International Statistical Classification of Diseases and Related Health Problems (ICD-11). We provide a diagnostic framework for classifying symptoms using the existing diagnostic categories: psychotic condition due to a general medical condition, brief psychotic disorder, delirium, and HACE. We also discuss the potential classification of isolated HA psychosis into those categories. A valid and reproducible classification of symptoms is essential for communication among professionals, ensuring that patients receive optimal treatment, planning further trips to HA for individuals who have experienced psychosis at HA, and advancing research in the field.

Objective Umbrella reviews are a new form of literature review that summarises the strength and/or quality of the evidence from all systematic reviews and meta-analyses conducted on a broad topic. This type of review thus provides an exhaustive examination of a vast body of information, providing the highest synthesis of knowledge. A critical strength of umbrella reviews is recalculating the meta-analytic estimates within a uniform framework to allow a consistent evidence stratification. To our best knowledge, there is no comprehensive package or software to conduct umbrella reviews.Methods The R package metaumbrella accomplishes this aim by building on three core functions that (1) automatically perform all required calculations in an umbrella review (including but not limited to pairwise meta-analyses), (2) stratify evidence according to various classification criteria and (3) generate a visual representation of the results. In addition, this package allows flexible inputs for each review or meta-analysis analysed (eg, means plus SD, or effect size estimate and CI) and customisation (eg, stratification criteria following Ioannidis, algorithmic GRADE or personalised classification).Results The R package metaumbrella thus provides the first comprehensive range of facilities to perform umbrella reviews with stratification of the evidence.Conclusion To facilitate the use of this package, even for researchers unfamiliar with R, we also provide a JAMOVI module and an open-access, browser-based graphical interface that allow use of the core functions of the package with a few mouse clicks.

Background: The clinical high risk for psychosis (CHR-P) construct represents an opportunity for prevention and early intervention in young adults, but the relationship between risk for psychosis and physical health in these patients remains unclear. Methods: We conducted a RECORD-compliant clinical register-based cohort study, selecting the long-term cumulative risk of developing a persistent psychotic disorder as the primary outcome. We investigated associations between primary outcome and physical health data with Electronic Health Records at the South London and Maudsley (SLaM) NHS Trust, UK (January 2013–October 2020). We performed survival analyses using Kaplan-Meier curves, log-rank tests, and Cox proportional hazard models. Results: The database included 137 CHR-P subjects; 21 CHR-P developed psychosis during follow-up, and the cumulative incidence of psychosis risk was 4.9% at 1 year and 56.3% at 7 years. Log-rank tests suggested that psychosis risk might change between different levels of nicotine and alcohol dependence. Kaplan-Meier curve analyses indicated that non-hazardous drinkers may have a lower psychosis risk than non-drinkers. In the Cox proportional hazard model, nicotine dependence presented a hazard ratio of 1.34 (95% CI: 1.1–1.64) (p = 0.01), indicating a 34% increase in psychosis risk for every additional point on the Fagerström Test for Nicotine Dependence. Conclusions: Our findings suggest that a comprehensive assessment of tobacco and alcohol use, diet, and physical activity in CHR-P subjects is key to understanding how physical health contributes to psychosis risk.

Abstract Individuals at Clinical High Risk for Psychosis (CHR-P) demonstrate heterogeneity in clinical profiles and outcome features. However, the extent of neuroanatomical heterogeneity in the CHR-P state is largely undetermined. We aimed to quantify the neuroanatomical heterogeneity in structural magnetic resonance imaging measures of cortical surface area (SA), cortical thickness (CT), subcortical volume (SV), and intracranial volume (ICV) in CHR-P individuals compared with healthy controls (HC), and in relation to subsequent transition to a first episode of psychosis. The ENIGMA CHR-P consortium applied a harmonised analysis to neuroimaging data across 29 international sites, including 1579 CHR-P individuals and 1243 HC, offering the largest pooled CHR-P neuroimaging dataset to date. Regional heterogeneity was indexed with the Variability Ratio (VR) and Coefficient of Variation (CV) ratio applied at the group level. Personalised estimates of heterogeneity of SA, CT and SV brain profiles were indexed with the novel Person-Based Similarity Index (PBSI), with two complementary applications. First, to assess the extent of within-diagnosis similarity or divergence of neuroanatomical profiles between individuals. Second, using a normative modelling approach, to assess the ‘normativeness’ of neuroanatomical profiles in individuals at CHR-P. CHR-P individuals demonstrated no greater regional heterogeneity after applying FDR corrections. However, PBSI scores indicated significantly greater neuroanatomical divergence in global SA, CT and SV profiles in CHR-P individuals compared with HC. Normative PBSI analysis identified 11 CHR-P individuals (0.70%) with marked deviation (>1.5 SD) in SA, 118 (7.47%) in CT and 161 (10.20%) in SV. Psychosis transition was not significantly associated with any measure of heterogeneity. Overall, our examination of neuroanatomical heterogeneity within the CHR-P state indicated greater divergence in neuroanatomical profiles at an individual level, irrespective of psychosis conversion. Further large-scale investigations are required of those who demonstrate marked deviation.

BackgroundThe clinical high-risk for psychosis (CHR) paradigm is one of the best studied preventive paradigms in psychiatry. However, most studies have been conducted in high-income countries. It is unclear if knowledge from such countries applies to low and middle-income countries (LAMIC), and if there are specific limitations hindering CHR research there. Our aim is to systematically review studies on CHR from LAMIC.MethodsA multistep PRISMA-compliant literature search was performed in PubMed and Web of Science for articles published until 1/03/2022, conducted in LAMIC, addressing the concept and correlates of CHR. Study characteristics as well as limitations were reported. Corresponding authors of the included studies were invited to answer an online poll. Quality assessment was done with the MMAT.ResultsA total of 109 studies were included in the review: none from low-income countries, 8 from lower middle-income countries, and 101 from upper middle-income countries. The most frequent limitations were small sample size (47.9%), cross-sectional design (27.1%), and follow-up issues (20.8%). Mean quality of included studies was of 4.4. Out of the 43 corresponding authors, 12 (27.9%) completed the online poll. They cited further limitations as few financial resources (66.7%), no involvement of population (58.2%) and cultural barriers (41.7%). Seventy five percent researchers reported that CHR research should be conducted differently in LAMIC compared to high-income countries, due to structural and cultural issues. Stigma was mentioned in three out of five sections of the poll.DiscussionResults show the discrepancy of available evidence on CHR in LAMIC, given the shortage of resources in such countries. Future directions should aim to increase the knowledge on individuals at CHR in such settings, and to address stigma and cultural factors that may play a role in the pathways toward care in psychosis.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=316816, CRD42022316816.

IntroductionThe impact of the clinical high-risk for psychosis (CHR-P) construct is dependent on accurately predicting outcomes. Individuals with brief limited intermittent psychotic symptoms (BLIPS) have higher risk of developing a first episode of psychosis (FEP) compared to individuals with attenuated psychotic symptoms (APS). Supplementing subgroup stratification with information from candidate biomarkers based on neurobiological parameters, such as resting-state, regional cerebral blood flow (rCBF), may help refine risk estimates. Based on previous evidence, we hypothesized that individuals with BLIPS would exhibit increased rCBF compared to APS in key regions linked to dopaminergic pathways.MethodsData from four studies were combined using ComBat (to account for between-study differences) to analyse rCBF in 150 age- and sex-matched subjects (n = 30 healthy controls [HCs], n = 80 APS, n = 20 BLIPS and n = 20 FEP). Global gray matter (GM) rCBF was examined in addition to region-of-interest (ROI) analyses in bilateral/left/right frontal cortex, hippocampus and striatum. Group differences were assessed using general linear models: (i) alone; (ii) with global GM rCBF as a covariate; (iii) with global GM rCBF and smoking status as covariates. Significance was set at p 0.05). All results were robust to addition of covariates (p > 0.05). No significant clusters were identified in whole-brain voxel-wise analyses (p > 0.05FWE). Weak-to-moderate evidence was found for an absence of rCBF differences between APS and BLIPS in Bayesian ROI analyses.ConclusionOn this evidence, APS and BLIPS are unlikely to be neurobiologically distinct. Due to this and the weak-to-moderate evidence for the null hypothesis, future research should investigate larger samples of APS and BLIPS through collaboration across large-scale international consortia.

Abstract This study aims to meta-analytically characterize the presence and magnitude of within-group variability across neurocognitive functioning in young people at Clinical High-Risk for psychosis (CHR-P) and comparison groups. Multistep, PRISMA/MOOSE-compliant systematic review (PROSPERO-CRD42020192826) of the Web of Science database, Cochrane Central Register of Reviews and Ovid/PsycINFO and trial registries up to July 1, 2020. The risk of bias was assessed using a modified version of the NOS for cohort and cross-sectional studies. Original studies reporting neurocognitive functioning in individuals at CHR-P compared to healthy controls (HC) or first-episode psychosis (FEP) patients were included. The primary outcome was the random-effect meta-analytic variability ratios (VR). Secondary outcomes included the coefficient of variation ratios (CVR). Seventy-eight studies were included, relating to 5162 CHR-P individuals, 2865 HC and 486 FEP. The CHR-P group demonstrated higher variability compared to HC (in descending order of magnitude) in visual memory (VR: 1.41, 95% CI 1.02–1.94), executive functioning (VR: 1.31, 95% CI 1.18–1.45), verbal learning (VR: 1.29, 95% CI 1.15–1.45), premorbid IQ (VR: 1.27, 95% CI 1.09–1.49), processing speed (VR: 1.26, 95% CI 1.07–1.48), visual learning (VR: 1.20, 95% CI 1.07–1.34), and reasoning and problem solving (VR: 1.17, 95% CI 1.03–1.34). In the CVR analyses the variability in CHR-P population remains in the previous neurocognitive domains and emerged in attention/vigilance, working memory, social cognition, and visuospatial ability. The CHR-P group transitioning to psychosis showed greater VR in executive functioning compared to those not developing psychosis and compared to FEP groups. Clinical high risk for psychosis subjects shows increased variability in neurocognitive performance compared to HC. The main limitation of this study is the validity of the VR and CVR as an index of variability which has received debate. This finding should be explored by further individual-participant data research and support precision medicine approaches.

Background: Structural magnetic resonance imaging studies in individuals at clinical high risk (CHR) for psychosis have yielded conflicting results. Methods: The aims of this study were to compare intracranial and structural brain volumes and variability of CHR individuals with those of healthy control (HC) subjects and to investigate brain volume differences and variability in CHR subjects with and without transition to psychosis. The PubMed and Embase databases were searched for relevant studies published before June 1, 2020. Results: A total of 34 studies were deemed eligible, which included baseline data of 2111 CHR and 1472 HC participants. In addition, data were included for 401 CHR subjects who subsequently transitioned to psychosis and 1023 nontransitioned CHR participants. Whole-brain and left, right, and bilateral hippocampal volume were significantly smaller in CHR subjects than in HC subjects. Cerebrospinal fluid and lateral ventricle volumes were significantly larger in CHR subjects than in HC subjects. Variability was not significantly different in CHR subjects compared with HC subjects. CHR individuals with and without subsequent transition to psychosis did not show significant differences in any of the volumetric assessments or in variability. Conclusions: This meta-analysis demonstrates reduced whole-brain and hippocampal volumes and increased cerebrospinal fluid and lateral ventricle volumes in CHR individuals. However, no significant differences were observed in any of the volumetric assessments between CHR individuals with and without subsequent transition to psychosis. These findings suggest that although structural brain alterations are present before the onset of the disorder, they may not significantly contribute to the identification of CHR individuals at the highest risk for the development of psychosis.

Abstract Clinical High Risk for Psychosis (CHR-P) services have been primarily developed to support young people with attenuated symptoms (indicated prevention). No evidence-based appraisal has systematically investigated to what extent these clinics may implement other preventive approaches. PRISMA 2020-compliant systematic review of Web of Science, Cochrane Central Register of Reviews, and Ovid/PsychINFO, from inception until 14th June 2021, identifying original studies describing public health strategies: (a) service characteristics (configuration of mental health service, outreach, pathways to care); (b) universal interventions (general population); (c) selective interventions targeting CHR-P service-users or family/carers. Public health preventive initiatives were systematically stratified according to core social determinants of mental disorders associated with the 2030 Sustainable Development Goals promoted by the United Nations Member States (UN 2030 SDG) and good mental health outcomes. A total of 66 publications were included, providing data on 13 standalone, 40 integrated, three networks, and six regional or international surveys of CHR-P services across Europe, Asia, Oceania, Africa, North and South America, providing care to >28 M people. CHR-P services implement numerous public health initiatives targeting social and cultural (16 initiatives), economic (seven initiatives), demographic (six initiatives), environmental events (four initiatives) and neighbourhood (three initiatives) UN 2030 SGD determinants of mental disorders. There is additional evidence for CHR-P services promoting good mental health. The main barriers were the lack of resources for expanding public health prevention at a large scale. CHR-P services implement numerous public health prevention initiatives and promotion of good mental health beyond indicated prevention of psychosis.

Introduction People often experience significant difficulties in receiving mental healthcare due to insufficient resources, stigma and lack of access to care. Remote care technology has the potential to overcome these barriers by reducing travel time and increasing frequency of contact with patients. However, the safe delivery of remote mental healthcare requires evidence on which aspects of care are suitable for remote delivery and which are better served by in-person care. We aim to investigate clinical and demographic associations with remote mental healthcare in a large electronic health record (EHR) dataset and the degree to which remote care is associated with differences in clinical outcomes using natural language processing (NLP) derived EHR data.Methods and analysis Deidentified EHR data, derived from the South London and Maudsley (SLaM) National Health Service Foundation Trust Biomedical Research Centre (BRC) Case Register, will be extracted using the Clinical Record Interactive Search tool for all patients receiving mental healthcare between 1 January 2019 and 31 March 2022. First, data on a retrospective, longitudinal cohort of around 80 000 patients will be analysed using descriptive statistics to investigate clinical and demographic associations with remote mental healthcare and multivariable Cox regression to compare clinical outcomes of remote versus in-person assessments. Second, NLP models that have been previously developed to extract mental health symptom data will be applied to around 5 million documents to analyse the variation in content of remote versus in-person assessments.Ethics and dissemination The SLaM BRC Case Register and Clinical Record Interactive Search (CRIS) tool have received ethical approval as a deidentified dataset (including NLP-derived data from unstructured free text documents) for secondary mental health research from Oxfordshire REC C (Ref: 18/SC/0372). The study has received approval from the SLaM CRIS Oversight Committee. Study findings will be disseminated through peer-reviewed, open access journal articles and service user and carer advisory groups.

Abstract Aims This study aimed to summarize the evidence on sleep alterations in medication-naïve children and adolescents with autism spectrum disorder (ASD). Methods We systematically searched PubMed/Medline, Embase and Web of Science databases from inception through March 22, 2021. This study was registered with PROSPERO (CRD42021243881). Any observational study was included that enrolled medication-naïve children and adolescents with ASD and compared objective (actigraphy and polysomnography) or subjective sleep parameters with typically developing (TD) counterparts. We extracted relevant data such as the study design and outcome measures. The methodological quality was assessed through the Newcastle-Ottawa Scale (NOS). A meta-analysis was carried out using the random-effects model by pooling effect sizes as Hedges’ g. To assess publication bias, Egger’s test and p-curve analysis were done. A priori planned meta-regression and subgroup analysis were also performed to identify potential moderators. Results Out of 4277 retrieved references, 16 studies were eligible with 981 ASD patients and 1220 TD individuals. The analysis of objective measures showed that medication-naïve ASD patients had significantly longer sleep latency (Hedges’ g 0.59; 95% confidence interval [95% CI] 0.26 to 0.92), reduced sleep efficiency (Hedges’ g −0.58; 95% CI −0.87 to −0.28), time in bed (Hedges’ g −0.64; 95% CI −1.02 to −0.26) and total sleep time (Hedges’ g −0.64; 95% CI −1.01 to −0.27). The analysis of subjective measures showed that they had more problems in daytime sleepiness (Hedges’ g 0.48; 95% CI 0.26 to 0.71), sleep latency (Hedges’ g 1.15; 95% CI 0.72 to 1.58), initiating and maintaining sleep (Hedges’ g 0.86; 95% CI 0.39 to 1.33) and sleep hyperhidrosis (Hedges’ g 0.48; 95% CI 0.29 to 0.66). Potential publication bias was detected for sleep latency, sleep period time and total sleep time measured by polysomnography. Some sleep alterations were moderated by age, sex and concurrent intellectual disability. The median NOS score was 8 (interquartile range 7.25–8.75). Conclusion We found that medication-naïve children and adolescents with ASD presented significantly more subjective and objective sleep alterations compared to TD and identified possible moderators of these differences. Future research requires an analysis of how these sleep alterations are linked to core symptom severity and comorbid behavioural problems, which would provide an integrated therapeutic intervention for ASD. However, our results should be interpreted in light of the potential publication bias.

IntroductionIndicated primary prevention of psychosis is recommended by NICE clinical guidelines, but implementation research on Clinical High Risk for Psychosis (CHR-P) services is limited.MethodsElectronic audit of CHR-P services in England, conducted between June and September 2021, addressing core implementation domains: service configuration, detection of at-risk individuals, prognostic assessment, clinical care, clinical research, and implementation challenges, complemented by comparative analyses across service model. Descriptive statistics, Fisher's exact test and Mann-Whitney U-tests were employed.ResultsTwenty-four CHR-P clinical services (19 cities) were included. Most (83.3%) services were integrated within other mental health services; only 16.7% were standalone. Across 21 services, total yearly caseload of CHR-P individuals was 693 (average: 33; range: 4–115). Most services (56.5%) accepted individuals aged 14–35; the majority (95.7%) utilized the Comprehensive Assessment of At Risk Mental States (CAARMS). About 65% of services reported some provision of NICE-compliant interventions encompassing monitoring of mental state, cognitive-behavioral therapy (CBT), and family interventions. However, only 66.5 and 4.9% of CHR-P individuals actually received CBT and family interventions, respectively. Core implementation challenges included: recruitment of specialized professionals, lack of dedicated budget, and unmet training needs. Standalone services reported fewer implementation challenges, had larger caseloads (p = 0.047) and were more likely to engage with clinical research (p = 0.037) than integrated services.DiscussionWhile implementation of CHR-P services is observed in several parts of England, only standalone teams appear successful at detection of at-risk individuals. Compliance with NICE-prescribed interventions is limited across CHR-P services and unmet needs emerge for national training and investments.

Abstract Recent work has suggested that disorganised speech might be a powerful predictor of later psychotic illness in clinical high risk subjects. To that end, several automated measures to quantify disorganisation of transcribed speech have been proposed. However, it remains unclear which measures are most strongly associated with psychosis, how different measures are related to each other and what the best strategies are to collect speech data from participants. Here, we assessed whether twelve automated Natural Language Processing markers could differentiate transcribed speech excerpts from subjects at clinical high risk for psychosis, first episode psychosis patients and healthy control subjects (total N = 54). In-line with previous work, several measures showed significant differences between groups, including semantic coherence, speech graph connectivity and a measure of whether speech was on-topic, the latter of which outperformed the related measure of tangentiality. Most NLP measures examined were only weakly related to each other, suggesting they provide complementary information. Finally, we compared the ability of transcribed speech generated using different tasks to differentiate the groups. Speech generated from picture descriptions of the Thematic Apperception Test and a story re-telling task outperformed free speech, suggesting that choice of speech generation method may be an important consideration. Overall, quantitative speech markers represent a promising direction for future clinical applications.

Objetivo: Graduar as evidências sobre fatores de risco de transtornos alimentares (anorexia nervosa, bulimia nervosa e transtorno de compulsão alimentar periódica) com o método de revisão guarda-chuva. Métodos: Trata-se de revisão sistemática de estudos observacionais sobre fatores de risco de transtornos alimentares publicados no PubMed, PsycInfo, e Embase até 11 de dezembro de 2019. Recalculamos metanálises de efeitos aleatórios, heterogeneidade, efeito de estudo pequeno, viés de excesso de significância e intervalo de confiança de 95% e graduamos evidências significativas (p < 0,05) de convincentes a fracas, conforme os critérios estabelecidos. A qualidade foi avaliada com a ferramenta Assessment of Multiple Systematic Reviews 2 (AMSTAR-2). Resultados: Foram incluídas 9 das 2.197 metanálises, as quais apresentavam evidências de 50 fatores de risco, 29.272 sujeitos com transtornos alimentares e 1.679.385 controles. Embora não houvesse associação com evidências convincentes, evidências altamente sugestivas apoiaram a associação entre abuso sexual infantil e bulimia nervosa (k = 29, 1.103 casos com distúrbios alimentares, 8.496 controles, RC, 2,73, IC95% 1,96-3.79, p = 2,1x10-9, qualidade AMSTAR-2 moderada) e entre vitimização por provocação relacionada à aparência e quaisquer transtornos alimentares (k = 10, 1.341 casos com transtornos alimentares, 3.295 controles, RC 2,91, IC95% 2,05-4,12, p = 1,8x10-9, qualidade AMSTAR-2 moderada). Evidências sugestivas, fracas ou nenhuma evidência sustentaram 11, 29 e 8 associações, respectivamente. Conclusões: Evidência mais confiáveis indicam que eventos traumáticos e estressantes precoces são fatores de risco de transtornos alimentares. São necessários estudos de coorte colaborativos prospectivos maiores para identificar fatores de risco de transtornos alimentares, especialmente a anorexia nervosa

The impact of timing of antipsychotics and benzodiazepine treatment during a first episode of psychosis on clinical outcomes is unknown. We present a RECORD-compliant electronic health record cohort study including patients (n = 4,483, aged 14–35) with a primary diagnosis of any non-organic ICD-10 first episode of psychosis at SLAM-NHS between 2007 and 2017. The impact of antipsychotic timing (prescription > 1 week after a first episode of psychosis) was assessed on the primary outcome (risk of any psychiatric inpatient admission over 6 years), and secondary outcomes (cumulative duration of any psychiatric/medical/accident/emergency [A&E] admission over 6 years). The impact of prescribing benzodiazepine before antipsychotic at any point and of treatment patterns (antipsychotic alone, benzodiazepine alone, combination of antipsychotic with benzodiazepine) within the first week after a first episode of psychosis were also assessed. Survival analyses and zero-inflated negative binomial regressions, adjusted for core covariates, and complementary analyses were employed. Antipsychotic prescribed >1 week after a first episode of psychosis did not affect the risk of any psychiatric admission (HR = 1.04, 95% CI = 0.92–1.17, p = 0.557), but increased the duration of any psychiatric (22–28%), medical (78–35%) and A&E (30–34%) admission (months 12–72). Prescribing benzodiazepine before antipsychotic at any point did not affect the risk of any psychiatric admission (HR = 1.03, 95% CI = 0.94–1.13, p = 0.535), but reduced the duration of any psychiatric admission (17–24%, months 12–72), and increased the duration of medical (71–45%, months 12–72) and A&E (26–18%, months 12–36) admission. Prescribing antipsychotic combined with benzodiazepine within the first week after a first episode of psychosis showed better overall clinical outcomes than antipsychotic or benzodiazepine alone. Overall, delaying antipsychotic 1 week after a first episode of psychosis may worsen some clinical outcomes. Early benzodiazepine treatment can be considered with concomitant antipsychotic but not as standalone intervention.

Abstract Background Early identification and intervention of individuals with risk factors for or subtle prodromal symptoms of bipolar disorders (BD) may improve the illness course and prevent adverse long-term consequences. Methods We examined sociodemographic, clinical and psychopathological characteristics of help-seeking adolescents and young adults who consulted the Early Detection and Intervention Center Dresden at the University of Dresden (Germany) and presented with or without pre-defined at-risk criteria for BD. The standardized diagnostic procedure for all help-seeking youth included a comprehensive psychiatric history and a structured clinical interview. When BD at-risk state was suspected, early detection instruments (EPIbipolar, BPSS-FP) were applied. Treatment recommendations were formulated in multi-professional case conferences. Results Out of 890 help-seeking persons between 05/2009 and 04/2018, 582 (65%) completed the diagnostic process. Of these, 24 (4%) had manifest BD and 125 (21%) fulfilled at-risk BD criteria (age = 23.9 ± 0.6 years, female = 62%). Of the pre-defined main risk factors, family history for BD was reported in 22% of the at-risk persons, (hypo-)mania risk state in 44%, and increasing cyclothymic mood swings with increased activity in 48%. The most common secondary risk factors were decreased psychosocial functioning (78%), lifetime diagnosis of depressive disorder (67%) and specific sleep/circadian rhythm disturbances (59%). Substance use was very common in subjects at-risk for BD (cannabis = 50%, alcohol = 33%) and highest in patients with BD (cannabis = 75%, alcohol = 40%). Psychiatric treatment history, including psychopharmacological therapy, was similar between the groups, while treatment recommendations differed, with more advice for psychotherapy and antidepressants in the at-risk group with a lifetime diagnosis of depression and more advice for specialized BD treatment including mood stabilizers in patients with BD. Conclusion This analysis on the phenomenology of different BD at-risk stages suggests that early detection of individuals presenting with suggested risk factors for the development of BD is feasible in help-seeking young people. Future research should further develop/test stage-specific prevention and early targeted intervention approaches that were described in a naturalistic setting.

Abstract The first rate-limiting step to successfully translate prevention of psychosis in to clinical practice is to establish specialised Clinical High Risk for Psychosis (CHR-P) services. This study systematises the knowledge regarding CHR-P services and provides guidelines for translational implementation. We conducted a PRISMA/MOOSE-compliant (PROSPERO-CRD42020163640) systematic review of Web of Science to identify studies until 4/05/2020 reporting on CHR-P service configuration, outreach strategy and referrals, service user characteristics, interventions, and outcomes. Fifty-six studies (1998–2020) were included, encompassing 51 distinct CHR-P services across 15 countries and a catchment area of 17,252,666 people. Most services (80.4%) consisted of integrated multidisciplinary teams taking care of CHR-P and other patients. Outreach encompassed active (up to 97.6%) or passive (up to 63.4%) approaches: referrals came mostly (90%) from healthcare agencies. CHR-P individuals were more frequently males (57.2%). Most (70.6%) services accepted individuals aged 12–35 years, typically assessed with the CAARMS/SIPS (83.7%). Baseline comorbid mental conditions were reported in two-third (69.5%) of cases, and unemployment in one third (36.6%). Most services provided up to 2-years (72.4%), of clinical monitoring (100%), psychoeducation (81.1%), psychosocial support (73%), family interventions (73%), individual (67.6%) and group (18.9%) psychotherapy, physical health interventions (37.8%), antipsychotics (87.1%), antidepressants (74.2%), anxiolytics (51.6%), and mood stabilisers (38.7%). Outcomes were more frequently ascertained clinically (93.0%) and included: persistence of symptoms/comorbidities (67.4%), transition to psychosis (53.5%), and functional status (48.8%). We provide ten practical recommendations for implementation of CHR-P services. Health service knowledge summarised by the current study will facilitate translational efforts for implementation of CHR-P services worldwide.

The presence of a positive family relationship has been suggested as a protective factor from parental stress and from the development of full-blown psychosis. However, to date, there is limited research on family functioning in adolescents with psychosis and at clinical high risk for psychosis (CHR-P). This study is aimed at comparing family functioning and perceived stress in parents of adolescents with either CHR-P, early onset psychosis (EOP), or other psychiatric disorders (no CHR-P). As a secondary aim, it will correlate family functioning with parental perceived stress in order to find critical targets of intervention. We conducted a Reporting of Studies Conducted Using Observational Routinely-Collected Health Data (RECORD)—compliant, real-world, cross-sectional study. One-hundred and eleven adolescents aged 12–17 who access the institute of hospitalization and care with scientific character (IRCCS) Mondino Foundation Neuropsychiatric services (Pavia, Italy) between 2017 and 2020 and their parents (n = 222) were included. Sociodemographic characteristics of adolescents and their parents were collected. Family functioning was evaluated through the Family Adaptability and Cohesion Evaluation Scale-IV (FACES-IV) and the level of stress through the Perceived Stress Scale (PSS). Twenty adolescents had EOP, 38 had CHR-P, and 59 had no CHR-P. In total, 2.6% of CHR-P adolescents were adopted, 76.3% had separated-divorced parents, and 34.2% of parents had a depressive disorder. Among the FACES-IV sub-scale, maternal rigidity was progressively increased from no-CHR-P to CHR-P to EOP group, with statistical differences between EOP and the other two groups (p = 0.01). CHR-P mothers and fathers showed a high level of PSS values, without group difference. Lastly, PSS values correlated positively with the Rigidity, Disengagement, and Chaos scale of FACES-IV and negatively with the Communication scale (p < 0.05). Our results suggest that family functioning has a central role and could represent a worthwhile target of intervention for adolescents at CHR-P, leading the way to new preventive approaches.

Objective To investigate the associations of symptoms of mania and depression with clinical outcomes in people with unipolar depression.Design A natural language processing electronic health record study. We used network analysis to determine symptom network structure and multivariable Cox regression to investigate associations with clinical outcomes.Setting The South London and Maudsley Clinical Record Interactive Search database.Participants All patients presenting with unipolar depression between 1 April 2006 and 31 March 2018.Exposure (1) Symptoms of mania: Elation; Grandiosity; Flight of ideas; Irritability; Pressured speech. (2) Symptoms of depression: Disturbed mood; Anhedonia; Guilt; Hopelessness; Helplessness; Worthlessness; Tearfulness; Low energy; Reduced appetite; Weight loss. (3) Symptoms of mania or depression (overlapping symptoms): Poor concentration; Insomnia; Disturbed sleep; Agitation; Mood instability.Main outcomes (1) Bipolar or psychotic disorder diagnosis. (2) Psychiatric hospital admission.Results Out of 19 707 patients, at least 1 depression, overlapping or mania symptom was present in 18 998 (96.4%), 15 954 (81.0%) and 4671 (23.7%) patients, respectively. 2772 (14.1%) patients subsequently developed bipolar or psychotic disorder during the follow-up period. The presence of at least one mania (HR 2.00, 95% CI 1.85 to 2.16), overlapping symptom (HR 1.71, 95% CI 1.52 to 1.92) or symptom of depression (HR 1.31, 95% CI 1.07 to 1.61) were associated with significantly increased risk of onset of a bipolar or psychotic disorder. Mania (HR 1.95, 95% CI 1.77 to 2.15) and overlapping symptoms (HR 1.76, 95% CI 1.52 to 2.04) were associated with greater risk for psychiatric hospital admission than symptoms of depression (HR 1.41, 95% CI 1.06 to 1.88).Conclusions The presence of mania or overlapping symptoms in people with unipolar depression is associated with worse clinical outcomes. Symptom-based approaches to defining clinical phenotype may facilitate a more personalised treatment approach and better predict subsequent clinical outcomes than psychiatric diagnosis alone.

BackgroundThe clinical high-risk for psychosis (CHR-P) paradigm was introduced to detect individuals at risk of developing psychosis and to establish preventive strategies. While current prediction of outcomes in the CHR-P state is based mostly on the clinical assessment of presenting features, several emerging biomarkers have been investigated in an attempt to stratify CHR-P individuals according to their individual trajectories and refine the diagnostic process. However, heterogeneity across subgroups is a key challenge that has limited the impact of the CHR-P prediction strategies, as the clinical validity of the current research is limited by a lack of external validation across sites and modalities. Despite these challenges, electroencephalography (EEG) biomarkers have been studied in this field and evidence suggests that EEG used in combination with clinical assessments may be a key measure for improving diagnostic and prognostic accuracy in the CHR-P state. The PSYSCAN EEG study is an international, multi-site, multimodal longitudinal project that aims to advance knowledge in this field.MethodsParticipants at 6 international sites take part in an EEG protocol including EEG recording, cognitive and clinical assessments. CHR-P participants will be followed up after 2 years and subcategorised depending on their illness progression regarding transition to psychosis. Differences will be sought between CHR-P individuals and healthy controls and between CHR-P individuals who transition and those who do not transition to psychosis using data driven computational analyses.DiscussionThis protocol addresses the challenges faced by previous studies of this kind to enable valid identification of predictive EEG biomarkers which will be combined with other biomarkers across sites to develop a prognostic tool in CHR-P. The PSYSCAN EEG study aims to pave the way for incorporating EEG biomarkers in the assessment of CHR-P individuals, to refine the diagnostic process and help to stratify CHR-P subjects according to risk of transition. This may improve our understanding of the CHR-P state and therefore aid the development of more personalized treatment strategies.

Objective: To grade the evidence about risk factors for eating disorders (anorexia nervosa, bulimia nervosa, and binge eating disorder) with an umbrella review approach. Methods: This was a systematic review of observational studies on risk factors for eating disorders published in PubMed/PsycInfo/Embase until December 11th, 2019. We recalculated random-effect meta-analyses, heterogeneity, small-study effect, excess significance bias and 95% prediction intervals, grading significant evidence (p < 0.05) from convincing to weak according to established criteria. Quality was assessed with the Assessment of Multiple Systematic Reviews 2 (AMSTAR-2) tool. Results: Of 2,197 meta-analyses, nine were included, providing evidence on 50 risk factors, 29,272 subjects with eating disorders, and 1,679,385 controls. Although no association was supported by convincing evidence, highly suggestive evidence supported the association between childhood sexual abuse and bulimia nervosa (k = 29, 1,103 cases with eating disorders, 8,496 controls, OR, 2.73, 95%CI 1.96-3.79, p = 2.1 x 10-9, AMSTAR-2 moderate quality) and between appearance-related teasing victimization and any eating disorder (k = 10, 1,341 cases with eating disorders, 3,295 controls, OR 2.91, 95%CI 2.05-4.12, p = 1.8x10-9, AMSTAR-2 moderate quality). Suggestive, weak, or no evidence supported 11, 29, and 8 associations, respectively. Conclusions: The most credible evidence indicates that early traumatic and stressful events are risk factors for eating disorders. Larger collaborative prospective cohort studies are needed to identify risk factors for eating disorders, particularly anorexia nervosa.

As COVID-19 becomes endemic, identifying vulnerable population groups for severe infection outcomes and defining rapid and effective preventive and therapeutic strategies remains a public health priority. We performed an umbrella review, including comprehensive studies (meta-analyses and systematic reviews) investigating COVID-19 risk for infection, hospitalization, intensive care unit (ICU) admission, and mortality in people with psychiatric disorders, and outlined evidence- and consensus-based recommendations for overcoming potential barriers that psychiatric patients may experience in preventing and managing COVID-19, and defining optimal therapeutic options and current research priorities in psychiatry. We searched Web of Science, PubMed, and Ovid/PsycINFO databases up to 17 January 2022 for the umbrella review. We synthesized evidence, extracting when available pooled odd ratio estimates for the categories “any mental disorder” and “severe mental disorders.” The quality of each study was assessed using the AMSTAR-2 approach and ranking evidence quality. We identified four systematic review/meta-analysis combinations, one meta-analysis, and three systematic reviews, each including up to 28 original studies. Although we rated the quality of studies from moderate to low and the evidence ranged from highly suggestive to non-significant, we found consistent evidence that people with mental illness are at increased risk of COVID-19 infection, hospitalization, and most importantly mortality, but not of ICU admission. The risk and the burden of COVID-19 in people with mental disorders, in particular those with severe mental illness, can no longer be ignored but demands urgent targeted and persistent action. Twenty-two recommendations are proposed to facilitate this process.

BackgroundIn mental health, comorbidities are the norm rather than the exception. However, current meta-analytic methods for summarizing the neural correlates of mental disorders do not consider comorbidities, reducing them to a source of noise and bias rather than benefitting from their valuable information.ObjectivesWe describe and validate a novel neuroimaging meta-analytic approach that focuses on comorbidities. In addition, we present the protocol for a meta-analysis of all major mental disorders and their comorbidities.MethodsThe novel approach consists of a modification of Seed-based d Mapping—with Permutation of Subject Images (SDM-PSI) in which the linear models have no intercept. As in previous SDM meta-analyses, the dependent variable is the brain anatomical difference between patients and controls in a voxel. However, there is no primary disorder, and the independent variables are the percentages of patients with each disorder and each pair of potentially comorbid disorders. We use simulations to validate and provide an example of this novel approach, which correctly disentangled the abnormalities associated with each disorder and comorbidity. We then describe a protocol for conducting the new meta-analysis of all major mental disorders and their comorbidities. Specifically, we will include all voxel-based morphometry (VBM) studies of mental disorders for which a meta-analysis has already been published, including at least 10 studies. We will use the novel approach to analyze all included studies in two separate single linear models, one for children/adolescents and one for adults.DiscussionThe novel approach is a valid method to focus on comorbidities. The meta-analysis will yield a comprehensive atlas of the neuroanatomy of all major mental disorders and their comorbidities, which we hope might help develop potential diagnostic and therapeutic tools.

Background: The clinical high risk for psychosis (CHR-P) phase represents an opportunity for prevention and early intervention in young adults, which also could focus on improving physical health trajectories. Methods: We conducted a RECORD-compliant clinical register-based cohort study. The primary outcome was to describe the physical health of assessed CHR-P individuals, obtained via Electronic Health Records at the South London and Maudsley (SLaM) NHS Foundation Trust, UK (January 2013–October 2020). Results: The final database included 194 CHR-P subjects (46% female). Mean age was 23.70 ± 5.12 years. Percentage of tobacco smokers was 41% (significantly higher than in the age-matched general population [24%]). We found that 49% of subjects who consumed alcohol had an AUDIT-C (Alcohol Use Disorder Identification Test) score above 5 (hazardous drinking), with an average score of 4.94 (significantly higher than in the general population [2.75]). Investigating diet revealed low fiber intake in most subjects and high saturated fat intake in 10% of the individuals. We found that 47% of CHR-P subjects met the UK recommended physical activity guidelines (significantly lower than in the general population [66%]). Physical parameters (e.g., weight, heart rate, blood pressure) were not significantly different from the general population. Conclusions: This evidence corroborates the need for monitoring physical health parameters in CHR-P subjects, to implement tailored interventions that target daily habits.

The putative risk/protective factors for several personality disorders remain unclear. The vast majority of published studies has assessed personality characteristics/traits rather than disorders. Thus, the current umbrella review of meta-analyses (MAs) aims to systematically assess risk or protective factors associated with personality disorders. We searched PubMed–MEDLINE/PsycInfo databases, up to August 31, 2020. Quality of MAs was assessed with AMSTAR-2, while the credibility of evidence for each association was assessed through standard quantitative criteria. Out of 571 initial references, five meta-analyses met inclusion criteria, encompassing 56 associations of 26 potential environmental factors for antisocial, dependent, borderline personality disorder, with a median of five studies per association, and median 214 cases per association. Overall, 35 (62.5%) of the associations were nominally significant. Six associations met class II (i.e., highly suggestive) evidence for borderline personality disorder, with large effect sizes involving childhood emotional abuse (OR = 28.15, 95% CI 14.76–53.68), childhood emotional neglect (OR = 22.86, 95% CI 11.55–45.22), childhood any adversities (OR = 14.32, 95% CI 10.80–18.98), childhood physical abuse (OR = 9.30, 95% CI 6.57–13.17), childhood sexual abuse (OR = 7.95, 95% CI 6.21–10.17), and childhood physical neglect (OR = 5.73, 95% CI 3.21–10.21), plus 16 further associations supported by class IV evidence. No risk factor for antisocial or dependent personality disorder was supported by class I, II, and III, but six and seven met class IV evidence, respectively. Quality of included meta-analyses was rated as moderate in two, critically low in three. The large effect sizes found for a broad range of childhood adversities suggest that prevention of personality disorders should target childhood-related risk factors. However, larger cohort studies assessing multidimensional risk factors are needed in the field.

ABSTRACT: Background: Little is known about clinical outcomes other than transition to psychosis in people at Clinical High-Risk for psychosis (CHR-P). Our aim was to comprehensively meta-analytically evaluate for the first time a wide range of clinical and functional outcomes beyond transition to psychosis in CHR-P individuals. Methods: PubMed and Web of Science were searched until November 2020 in this PRISMA compliant meta-analysis (PROSPERO:CRD42020206271). Individual longitudinal studies conducted in individuals at CHR-P providing data on at least one of our outcomes of interest were included. We carried out random-effects pairwise meta-analyses, meta-regressions, and assessed publication bias and study quality. Analyses were two-tailed with α=0.05. Findings: 75 prospective studies were included (n=5,288, age=20.0 years, females=44.5%). Attenuated positive symptoms improved at 12 (Hedges’ g=0.753, 95%CI=0.495-1.012) and 24 (Hedges’ g=0.836, 95%CI=0.463-1.209), but not ≥36 months (Hedges’ g=0.315. 95%CI=-0.176–0.806). Negative symptoms improved at 12 (Hedges’ g=0.496, 95%CI=0.315–0.678), but not 24 (Hedges’ g=0.499, 95%CI=-0.137–1.134) or ≥36 months (Hedges’ g=0.033, 95%CI=-0.439–0.505). Depressive symptoms improved at 12 (Hedges’ g=0.611, 95%CI=0.441–0.782) and 24 (Hedges’ g=0.583, 95%CI=0.364–0.803), but not ≥36 months (Hedges’ g=0.512 95%CI=-0.337–1.361). Functioning improved at 12 (Hedges’ g=0.711, 95%CI=0.488–0.934), 24 (Hedges’ g=0.930, 95%CI=0.553–1.306) and ≥36 months (Hedges’ g=0.392, 95%CI=0.117–0.667). Remission from CHR-P status occurred in 33.4% (95%CI=22.6–44.1%) at 12 months, 41.4% (95%CI=32.3–50.5%) at 24 months and 42.4% (95%CI=23.4–61.3%) at ≥36 months. Heterogeneity across the included studies was significant and ranged from I2=53.6% to I2=96.9%. The quality of the included studies (mean±SD) was 4.6±1.1 (range=2-8). Interpretation: CHR-P individuals improve on symptomatic and functional outcomes over time, but these improvements are not maintained in the longer term, and less than half fully remit. Prolonged duration of care may be needed for this patient population to optimize outcomes. Funding: None.

Background: Despite significant research progress surrounding precision medicine in psychiatry, there has been little tangible impact upon real-world clinical care. Objective: To identify barriers and facilitators affecting the real-world implementation of precision psychiatry. Method: A PRISMA-compliant systematic literature search of primary research studies, conducted in the Web of Science, Cochrane Central Register of Controlled Trials, PsycINFO and OpenGrey databases. We included a qualitative data synthesis structured according to the ‘Consolidated Framework for Implementation Research’ (CFIR) key constructs. Results: Of 93,886 records screened, 28 studies were suitable for inclusion. The included studies reported 38 barriers and facilitators attributed to the CFIR constructs. Commonly reported barriers included: potential psychological harm to the service user (n = 11), cost and time investments (n = 9), potential economic and occupational harm to the service user (n = 8), poor accuracy and utility of the model (n = 8), and poor perceived competence in precision medicine amongst staff (n = 7). The most highly reported facilitator was the availability of adequate competence and skills training for staff (n = 7). Conclusions: Psychiatry faces widespread challenges in the implementation of precision medicine methods. Innovative solutions are required at the level of the individual and the wider system to fulfil the translational gap and impact real-world care.

Objective To determine whether gender differences in symptom presentation at first episode psychosis (FEP) remain even when controlling for substance use, age and ethnicity, using natural language processing applied to electronic health records (EHRs).Design, setting and participants Data were extracted from EHRs of 3350 people (62% male patients) who had presented to the South London and Maudsley NHS Trust with a FEP between 1 April 2007 and 31 March 2017. Logistic regression was used to examine gender differences in the presentation of positive, negative, depressive, mania and disorganisation symptoms.Exposure(s) (for observational studies) Gender (male vs female).Main outcome(s) and measure(s) Presence of positive, negative, depressive, mania and disorganisation symptoms at initial clinical presentation.Results Eight symptoms were significantly more prevalent in men (poverty of thought, negative symptoms, social withdrawal, poverty of speech, aggression, grandiosity, paranoia and agitation). Conversely, tearfulness, low energy, reduced appetite, low mood, pressured speech, mood instability, flight of ideas, guilt, mutism, insomnia, poor concentration, tangentiality and elation were more prevalent in women than men. Negative symptoms were more common among men (OR 1.85, 95% CI 1.33 to 2.62) and depressive and manic symptoms more common among women (OR 0.30, 95% CI 0.26 to 0.35). After adjustment for illicit substance use, the strength of associations between gender and negative, manic and depression symptoms increased, whereas gender differences in aggression, agitation, paranoia and grandiosity became insignificant.Conclusions There are clear gender differences in the clinical presentation of FEP. Our findings suggest that gender can have a substantial influence on the nature of clinical presentation in people with psychosis, and that this is only partly explained by exposure to illicit substance use.

Abstract Background The European impact of the clinical high risk for psychosis (CHR-P) paradigm is constrained by the lack of critical mass (detection) to power prognostic and preventive interventions. Methods An ITAlian partnership for psychosis prevention (ITAPP) was created across CHR-P centers, which were surveyed to describe: (a) service, catchment area, and outreach; (b) service users; and (c) interventions and outcomes. Descriptive statistics and Kaplan–Meier failure function complemented the analyses. Results The ITAPP included five CHR-P clinical academic centers established from 2007 to 2018, serving about 13 million inhabitants, with a recruitment capacity of 277 CHR-P individuals (mean age: 18.7 years, SD: 4.8, range: 12–39 years; 53.1% females; 85.7% meeting attenuated psychotic symptoms; 85.8% without any substance abuse). All centers were multidisciplinary and included adolescents and young adults (transitional) primarily recruited through healthcare services. The comprehensive assessment of at-risk mental state was the most widely used instrument, while the duration of follow-up, type of outreach, and preventive interventions were heterogeneous. Across 205 CHR-P individuals with follow up (663.7 days ± 551.7), the cumulative risk of psychosis increased from 8.7% (95% CI 5.3–14.1) at 1 year to 15.9% (95% CI 10.6–23.3) at 2 years, 21.8% (95% CI 14.9–31.3) at 3 years, 34.8% (95% CI 24.5–47.9) at 4 years, and 51.9% (95% CI 36.3–69.6) at 5 years. Conclusions The ITAPP is one of the few CHR-P clinical research partnerships in Europe for fostering detection, prognosis, and preventive care, as well as for translating research innovations into practice.

AbstractBackgroundIndividuals at clinical high risk of psychosis (CHR-P) recruited in randomized clinical trials (RCTs) and observational cohorts may display a different enrichment and hence risk of transition to psychosis. No meta-analysis has ever addressed this issue.Methods“Preferred Reporting Items for Systematic reviews and Meta-Analyses” (PRISMA) and “Meta-analysis Of Observational Studies in Epidemiology” (MOOSE)–compliant meta-analysis. PubMed and Web of Science were searched until November 2020 (PROSPERO:CRD42021229223). We included nonoverlapping longitudinal studies (RCTs-control condition and observational cohorts) reporting the transition to psychosis in CHR-P individuals. The primary effect size measure was the cumulative risk of transition at 0.5, 1, and 2 years follow-up in RCTs compared to observational cohorts. Random effects meta-analyses, heterogeneity assessment, quality assessment, and meta-regressions were conducted.ResultsNinety-four independent studies (24 RCTs, 70 observational cohorts) and 9,243 individuals (mean age = 20.1 ± 3.0 years; 43.7% females) were included. The meta-analytical risk of transitioning to psychosis from a CHR-P stage was 0.091 (95% confidence intervals [CI] = 0.068–0.121) at 0.5 years, 0.140 (95% CI = 0.101–0.191) at 1 year and 0.165 (95% CI = 0.097–0.267) at 2 years follow-up in RCTs, and 0.081 (95% CI = 0.067–0.099) at 0.5 years, 0.138 (95% CI = 0.114–0.167) at 1 year, and 0.174 (95% CI = 0.156–0.193) at 2 years follow-up in observational cohorts. There were no between-group differences in transition risks (p > 0.05). The proportion of CHR-P individuals with substance use disorders (excluding alcohol and cannabis) was higher in observational cohorts (16.8, 95% CI = 13.3–21.0%) than in RCTs (3.4, 95% CI = 0.8–12.7%; p = 0.018).ConclusionsThere is no meta-analytic evidence supporting sampling biases in RCTs of CHR-P individuals. Further RCTs are needed to detect effective interventions to prevent psychosis in this at-risk group.

Abstract Background To determine the proportion of patients in symptomatic remission and recovery following a first-episode of psychosis (FEP). Methods A multistep literature search using the Web of Science database, Cochrane Central Register of Reviews, Ovid/PsychINFO, and trial registries from database inception to November 5, 2020, was performed. Cohort studies and randomized control trials (RCT) investigating the proportion of remission and recovery following a FEP were included. Two independent researchers searched, following PRISMA and MOOSE guidelines and using a PROSPERO protocol. We performed meta-analyses regarding the proportion of remission/recovery (symptomatic plus functional outcomes). Heterogeneity was measured employing Q statistics and I2 test. To identify potential predictors, meta-regression analyses were conducted, as well as qualitative reporting of studies included in a systematic review. Sensitivity analyses were performed regarding different times of follow-up and type of studies. Results One hundred articles (82 cohorts and 18 RCTs) were included in the meta-analysis. The pooled proportion of symptomatic remission was 54% (95%CI [30, 49–58]) over a mean follow-up period of 43.57 months (SD = 51.82) in 76 studies. After excluding RCT from the sample, the proportion of remission remained similar (55%). The pooled proportion of recovery was 32% (95%CI [27–36]) over a mean follow-up period of 71.85 months (SD = 73.54) in 40 studies. After excluding RCT from the sample, the recovery proportion remained the same. No significant effect of any sociodemographic or clinical predictor was found. Conclusions Half of the patients are in symptomatic remission around 4 years after the FEP, while about a third show recovery after 5.5 years.

Background: Most services for individuals at Clinical High Risk for Psychosis (CHR-P) provide short-term clinical care. This study determines the real-world and long-term clinical outcomes beyond transition to psychosis in a large cohort of CHR-P individuals. Method: Retrospective RECORD-compliant real-world Electronic Health Records (EHR) cohort study in secondary mental health care (the South London and the Maudsley -SLaM- NHS Foundation Trust). All CHR-P patients accessing the CHR-P service at SLaM in the period 2001–2018 were included. Main outcomes were long-term cumulative risk of first: (i) developing an ICD-10 psychotic disorder (primary outcome), receiving a treatment with (iia) antipsychotic medication, (iib) benzodiazepines, (iic) other psychotropic medications, (iid) psychotherapy, receiving an (iiia) informal or (iiib) compulsory admission into a mental health hospital, and the time to these events; (iiic) number of days spent in hospital and (iv) cumulative risk of death for any reason and age/gender Standardised Mortality Ratio (SMR). Data were extracted from the EHR and analysed with Kaplan Meier failure functions, Cox and zero-inflated negative binomial regressions. Findings: 600 CHR-P patients (80.43% Attenuated Psychotic Symptoms, APS; 18.06%, Brief and Limited Intermittent Psychotic Symptoms, BLIPS, 1.51% Genetic Risk and Deterioration Syndrome) were included (mean age 22.63 years, range 13–36; 55.33% males; 46.44% white, mean duration of untreated attenuated psychotic symptoms 676.32 days, 1105.40 SD). The cumulative risk to first psychosis was 0.365 (95%CI 0.302–0.437) at 11 years; first antipsychotic 0.777 (95%CI 0.702–0.844) at 9 years; first benzodiazepine 0.259 (95%CI 0.183–0.359) at 12 years; first other types of medications 0.630 (95%CI 0.538–0.772) at 9 years; first psychotherapy 0.814 (95%CI 0.764–0.859) at 9 years; first informal admission 0.378 (95%CI 0.249–0.546) at 12 years; first compulsory admission 0.251 (95%CI 0.175–0.352) at 12 years; those admitted spent on average 94.84 (SD=169.94) days in hospital; the cumulative risk of death for any reason was 0.036 (95%CI 0.012–0.103) at 9 years, with an SMR of 3.9 (95%CI 1.20–6.6). Compared to APS, BLIPS had a higher risk of developing psychosis, being admitted compulsorily into hospital, receiving antipsychotics and benzodiazepines and lower probability of receiving psychotherapy. Other prognostic factors of long-term outcomes included age, symptoms severity, duration of untreated attenuated psychotic symptoms, ethnicity and employment status. Interpretation: Duration of care provided by CHR-P services should be expanded to address long-term real-world outcomes. Funding: This study was supported by the King's College London Confidence in Concept award from the Medical Research Council (MRC) (MC_PC_16048) to PF-P. GSP is supported by the Alicia Koplowitz Foundation. HB is supported by a National Institute for Health Research Maudsley Biomedical Research Centre studentship.