Risk For Psychosis Research Articles

Duration of Untreated Prodromal Psychosis and Cognitive Impairments

The possible association between the duration of untreated prodromal symptoms (DUPrS) and cognitive functioning in individuals at clinical high risk (CHR) for psychosis remains underexplored. To investigate the intricate interplay between DUPrS, cognitive performance, and conversion outcomes, shedding light on the potential role of DUPrS in shaping cognitive trajectories and psychosis risk in individuals at CHR for psychosis. This cohort study of individuals at CHR for psychosis was conducted at the Shanghai Mental Health Center in China from January 10, 2016, to December 29, 2021. Participants at CHR for psychosis typically exhibit attenuated positive symptoms; they were identified according to the Structured Interview for Prodromal Syndromes, underwent baseline neuropsychological assessments, and were evaluated at a 3-year clinical follow-up. Data were analyzed from August 25, 2021, to May 10, 2023. Duration of untreated prodromal symptoms and cognitive impairments in individuals at CHR for psychosis. The primary study outcome was conversion to psychosis. The DUPrS was categorized into 3 groups based on percentiles (33rd percentile for short [≤3 months], 34th-66th percentile for median [4-9 months], and 67th-100th percentile for long [≥10 months]). The DUPrS, cognitive variables, and the risk of conversion to psychosis were explored through quantile regression and Cox proportional hazards regression analyses. This study included 506 individuals (median age, 19 [IQR, 16-21] years; 53.6% [n = 271] women). The mean (SD) DUPrS was 7.8 (6.857) months, and the median (IQR) was 6 (3-11) months. The short and median DUPrS groups displayed poorer cognitive performance than the long DUPrS group in the Brief Visuospatial Memory Test-Revised (BVMT-R) (Kruskal-Wallis χ2 = 8.801; P = .01) and Category Fluency Test (CFT) (Kruskal-Wallis χ2 = 6.670; P = .04). Quantile regression analysis revealed positive correlations between DUPrS rank and BVMT-R scores (<90th percentile of DUPrS rank) and CFT scores (within the 20th-70th percentile range of DUPrS rank). Among the 506 participants, 20.8% (95% CI, 17.4%-24.5%) converted to psychosis within 3 years. Cox proportional hazards regression analysis identified lower educational attainment (hazard ratio [HR], 0.912; 95% CI, 0.834-0.998), pronounced negative symptoms (HR, 1.044; 95% CI, 1.005-1.084), and impaired performance on the Neuropsychological Assessment Battery: Mazes (HR, 0.961; 95% CI, 0.924-0.999) and BVMT-R (HR, 0.949; 95% CI, 0.916-0.984) tests as factors associated with conversion. The finding of this cohort study suggest the intricate interplay between DUPrS, cognitive performance, and conversion risk in individuals at CHR for psychosis. The findings emphasize the importance of considering both DUPrS and cognitive functioning in assessing the trajectory of these individuals.

Reduced slow wave density is associated with worse positive symptoms in clinical high risk: An objective readout of symptom severity for early treatment interventions?

Individuals at clinical high risk for psychosis (CHR) present subsyndromal psychotic symptoms that can escalate and lead to the transition to a diagnosable psychotic disorder. Identifying biological parameters that are sensitive to these symptoms can therefore help objectively assess their severity and guide early interventions in CHR. Reduced slow wave oscillations (∼1 Hz) during non-rapid eye movement sleep were recently observed in first-episode psychosis patients and were linked to the intensity of their positive symptoms. Here, we collected overnight high-density EEG recordings from 37 CHR and 32 healthy control (HC) subjects and compared slow wave (SW) activity and other SW parameters (i.e., density and negative peak amplitude) between groups. We also assessed the relationships between clinical symptoms and SW parameters in CHR. While comparisons between HC and the entire CHR group showed no SW differences, CHR individuals with higher positive symptom severity (N = 18) demonstrated a reduction in SW density in an EEG cluster involving bilateral prefrontal, parietal, and right occipital regions compared to matched HC individuals. Furthermore, we observed a negative correlation between SW density and positive symptoms across CHR individuals, suggesting a potential target for early treatment interventions.

Risk of Psychosis Among Individuals Who Have Presented to Hospital With Self-harm: A Prospective Nationwide Register Study in Sweden.

Recent research showed that young people who presented to hospital with self-harm in Finland had a significantly elevated risk of later psychosis. We investigated the prospective relationship between hospital presentation for self-harm and risk of psychosis in an unprecedentedly large national Swedish cohort. We used inpatient and outpatient healthcare registers to identify all individuals born between 1981 and 1993 who were alive and living in Sweden on their 12th birthday and who presented to hospital one or more times with self-harm. We compared them with a matched cohort, followed up for up to 20 years, and compared the cumulative incidence of psychotic disorders. Furthermore, we examined whether the strength of the relationship between hospital presentation for self-harm and later psychosis changed over time by examining for cohort effects. In total, 28 908 (2.0%) individuals presented to hospital with self-harm without prior psychosis diagnosis during the follow-up. For individuals who presented to hospital with self-harm, the cumulative incidence of diagnosed psychosis was 20.7% at 20 years follow-up (hazard radio = 13.9, 95% CI 13.3-14.6, P-value <5 × 10-308). There was no evidence of a dilution of the effect over time: while the incidence of hospital self-harm presentation increased, this did not result in an attenuation over time of the strength of the relationship between hospital self-harm presentation and subsequent psychosis. Individuals who present to hospital with self-harm in their teens and 20s represent an important risk group for psychosis prediction and prevention.

Connectome dysfunction in patients at clinical high risk for psychosis and modulation by oxytocin

Abnormalities in functional brain networks (functional connectome) are increasingly implicated in people at Clinical High Risk for Psychosis (CHR-P). Intranasal oxytocin, a potential novel treatment for the CHR-P state, modulates network topology in healthy individuals. However, its connectomic effects in people at CHR-P remain unknown. Forty-seven men (30 CHR-P and 17 healthy controls) received acute challenges of both intranasal oxytocin 40 IU and placebo in two parallel randomised, double-blind, placebo-controlled cross-over studies which had similar but not identical designs. Multi-echo resting-state fMRI data was acquired at approximately 1 h post-dosing. Using a graph theoretical approach, the effects of group (CHR-P vs healthy control), treatment (oxytocin vs placebo) and respective interactions were tested on graph metrics describing the topology of the functional connectome. Group effects were observed in 12 regions (all pFDR < 0.05) most localised to the frontoparietal network. Treatment effects were found in 7 regions (all pFDR < 0.05) predominantly within the ventral attention network. Our major finding was that many effects of oxytocin on network topology differ across CHR-P and healthy individuals, with significant interaction effects observed in numerous subcortical regions strongly implicated in psychosis onset, such as the thalamus, pallidum and nucleus accumbens, and cortical regions which localised primarily to the default mode network (12 regions, all pFDR < 0.05). Collectively, our findings provide new insights on aberrant functional brain network organisation associated with psychosis risk and demonstrate, for the first time, that oxytocin modulates network topology in brain regions implicated in the pathophysiology of psychosis in a clinical status (CHR-P vs healthy control) specific manner.

Proteomic Biomarkers for the Prediction of Transition to Psychosis in Individuals at Clinical High Risk: A Multi-cohort Model Development Study.

Psychosis risk prediction is one of the leading challenges in psychiatry. Previous investigations have suggested that plasma proteomic data may be useful in accurately predicting transition to psychosis in individuals at clinical high risk (CHR). We hypothesized that an a priori-specified proteomic prediction model would have strong predictive accuracy for psychosis risk and aimed to replicate longitudinal associations between plasma proteins and transition to psychosis. This study used plasma samples from participants in 3 CHR cohorts: the North American Prodrome Longitudinal Studies 2 and 3, and the NEURAPRO randomized control trial (total n = 754). Plasma proteomic data were quantified using mass spectrometry. The primary outcome was transition to psychosis over the study follow-up period. Logistic regression models were internally validated, and optimism-corrected performance metrics derived with a bootstrap procedure. In the overall sample of CHR participants (age: 18.5, SD: 3.9; 51.9% male), 20.4% (n = 154) developed psychosis within 4.4 years. The a priori-specified model showed poor risk-prediction accuracy for the development of psychosis (C-statistic: 0.51 [95% CI: 0.50, 0.59], calibration slope: 0.45). At a group level, Complement C8B, C4B, C5, and leucine-rich α-2 glycoprotein 1 (LRG1) were associated with transition to psychosis but did not surpass correction for multiple comparisons. This study did not confirm the findings from a previous proteomic prediction model of transition from CHR to psychosis. Certain complement proteins may be weakly associated with transition at a group level. Previous findings, derived from small samples, should be interpreted with caution.

Differential expression of haptoglobin in individuals at clinical high risk of psychosis and its association with global functioning and clinical symptoms

BackgroundImmune dysregulation has been observed in patients with schizophrenia or first-episode psychosis, but few have examined dysregulation in those at clinical high-risk (CHR) for psychosis. The aim of this study was to examine whether the peripheral blood-based proteome was dysregulated in those with CHR. Secondly, we examined whether baseline dysregulation was related to current and future functioning and clinical symptoms. MethodsWe used data from participants of the North American Prodromal Longitudinal Studies (NAPLS) 2 and 3 (n = 715) who provided blood samples (Unaffected Comparison subjects (UC) n = 223 and CHR n = 483). Baseline proteomic data was quantified from plasma samples using mass spectrometry. Differential expression was examined between CHR and UC using logistic regression. Psychosocial functioning was measured using the Global Assessment of Functioning scale (GAF). Symptoms were measured using the subscale scores from the Scale of Psychosis-risk Symptoms; positive, negative, general, and disorganised. Three measures of each outcome were included: baseline, longest available follow-up (last follow-up) and most severe follow-up (MSF). Associations between the proteomic data, GAF and symptoms were assessed using ordinal regression. ResultsOf the 99 proteins quantified, six were differentially expressed between UC and CHR. However, only haptoglobin (HP) survived FDR-correction (OR:1.45, 95 %CI:1.23–1.69, padj = <0.001). HP was cross-sectionally and longitudinally associated with functioning and symptoms such that higher HP values were associated with poorer functioning and more severe symptoms. Results were evident after stringent adjustment and poorer functioning was observed in both NAPLS cohort separately. ConclusionWe demonstrate that elevated HP is robustly observed in those at CHR for psychosis, irrespective of transition to psychosis. HP is longitudinally associated with poorer functioning and greater symptom severity. These results agree with previous reports of increased HP gene expression in individuals at-risk for psychosis and with the dysfunction of the acute phase inflammatory response seen in psychotic disorders.

The Association of Hippocampal Long-Term Potentiation-Induced Gene Expression with Genetic Risk for Psychosis.

Genomic studies focusing on the contribution of common and rare genetic variants of schizophrenia and bipolar disorder support the view that substantial risk is conferred through molecular pathways involved in synaptic plasticity in the neurons of cortical and subcortical brain regions, including the hippocampus. Synaptic long-term potentiation (LTP) is central to associative learning and memory and depends on a pattern of gene expression in response to neuronal stimulation. Genes related to the induction of LTP have been associated with psychiatric genetic risk, but the specific cell types and timepoints responsible for the association are unknown. Using published genomic and transcriptomic datasets, we studied the relationship between temporally defined gene expression in hippocampal pyramidal neurons following LTP and enrichment for common genetic risk for schizophrenia and bipolar disorder, and for copy number variants (CNVs) and de novo coding variants associated with schizophrenia. We observed that upregulated genes in hippocampal pyramidal neurons at 60 and 120 min following LTP induction were enriched for common variant association with schizophrenia and bipolar disorder subtype I. At 60 min, LTP-induced genes were enriched in duplications from patients with schizophrenia, but this association was not specific to pyramidal neurons, perhaps reflecting the combined effects of CNVs in excitatory and inhibitory neuron subtypes. Gene expression following LTP was not related to enrichment for de novo coding variants from schizophrenia cases. Our findings refine our understanding of the role LTP-related gene sets play in conferring risk to conditions causing psychosis and provide a focus for future studies looking to dissect the molecular mechanisms associated with this risk.

The temporal association between social isolation, distress, and psychotic experiences in individuals at clinical high-risk for psychosis.

Psychotic experiences (PEs) and social isolation (SI) seem related during early stages of psychosis, but the temporal dynamics between the two are not clear. Literature so far suggests a self-perpetuating cycle wherein momentary increases in PEs lead to social withdrawal, which, subsequently, triggers PEs at a next point in time, especially when SI is associated with increased distress. The current study investigated the daily-life temporal associations between SI and PEs, as well as the role of SI-related and general affective distress in individuals at clinical high risk (CHR) for psychosis. We used experience sampling methodology in a sample of 137 CHR participants. We analyzed the association between SI, PEs, and distress using time-lagged linear mixed-effects models. SI did not predict next-moment fluctuations in PEs, or vice versa. Furthermore, although SI-related distress was not predictive of subsequent PEs, general affective distress during SI was a robust predictor of next-moment PEs. Our results suggest that SI and PEs are not directly related on a moment-to-moment level, but a negative emotional state when alone does contribute to the risk of PEs. These findings highlight the role of affective wellbeing during early-stage psychosis development.

The daily association between positive affect and psychotic experiences in individuals along the early stages of the psychosis continuum.

Psychosis often develops gradually along a continuum of severity. Little is known about the role of protective factors such as positive affect (PA) in the development of psychotic experiences (PEs). This study investigated i) the temporal (between-day) and contemporaneous (within-day) daily associations between PA and PEs in individuals at different early clinical stages for psychosis and ii) whether these associations differed per clinical stage. Daily diary data for 90 days came from 96 individuals at risk for psychosis, distributed over four subgroups defined according to the clinical staging model (stages 0-1b). We constructed multilevel models with PA as a predictor of PEs and vice versa. We investigated within- and between-person temporal and contemporaneous associations and tested whether these associations differed among early stages with multilevel moderation analyses. We found no within-person temporal effects between PA and PEs in either direction. Contemporaneously, current-day PA predicted current-day PEs (B = -0.14, p < 0.001) and vice versa (B = -0.61, p < 0.001). Between persons, more 90-day PA predicted fewer PEs in the temporal model (B = -0.14, p = 0.03). In addition, more 90-day PEs predicted PA in the temporal (B = -0.26, p < 0.001) and contemporaneous (B = -0.36, p < 0.001) models. The contemporaneous association between PA and PEs was stronger in individuals at ultra-high risk (UHR) for psychosis than in earlier stages. Our study supported a significant within-day, bidirectional relationship between PA and PEs. This suggests that a focus on PA and methods to improve PA may be an important addition to early intervention practices, particularly in those at UHR for psychosis.

An exploratory study of psychosis risk factors in individuals who are referred but do not meet criteria for an early intervention in psychosis service.

The 'at-risk mental state' (ARMS) for psychosis has been critiqued for its limited prognostic ability and identification of a limited proportion of those who will develop a first episode of psychosis (FEP). Broadening the search for high-risk groups is key to improving population-level ascertainment of psychosis risk. To explore risk enrichment in diagnostic, demographic and socio-functional domains among individuals referred to an early intervention in psychosis (EIP) service not meeting ARMS or FEP criteria. A retrospective file review of 16 years of referrals to a tertiary EIP service in Ireland was undertaken. Diagnostic outcomes from standardised assessments (Structured Clinical Interview for DSM), demographic (age, gender, family history, nationality) and socio-occupational (relationship status, living status, working status) variables were compiled for those not meeting criteria. These were compared with individuals diagnosed with an FEP in the same period. From 2005 to 2021 inclusive, of 2025 index assessments, 27.6% (n = 558) did not meet either FEP or ARMS criteria, which is notably higher than the 5.4% (n = 110) meeting ARMS criteria. This group had high psychiatric morbidity, with 65.4% meeting criteria for at least one DSM Axis I disorder. Depressive, anxiety and substance use disorders predominated. Their functional markers were poor, and comparable to the FEP cohort. This group is enriched for psychosis risk factors. They are a larger group than those meeting ARMS criteria, a finding that may reflect EIP service configuration. They may be an important focus for further study in the search for at-risk populations beyond the current ARMS model.

Addressing the elephant in the screening room: an item response theory analysis of the Prodromal Questionnaire (PQ-16) for at-risk symptoms of psychosis.

Within the context of patients at-risk of psychosis, where a variety of symptoms are present, identifying the most discriminative symptoms is essential for efficient detection and management. This cross-sectional online study analyzed individuals from the general population in order to better assess their risk of presenting symptoms belonging to the clinical high risk (CHR) for psychosis, called "CHR-related symptoms". The Prodromal Questionnaire-16 (PQ-16) served as a self-report screening tool. Item response theory (IRT) with a graded response model was used to assess the discrimination and difficulty of its criteria. The analysis included 936 participants (mean age: 21.5 years; 28.1% male, 71.9% female). "Déjà vu" stood out for its high discriminative power, while "Voices or whispers" and "Seen things" demonstrated strong precision relatively to the other CHR-related symptoms. Conversely, "Smell or taste" and "Changing face" were associated with the most severe cases relatively to the other CHR-related symptoms. This study identified the most indicative CHR-related symptoms to emphasize their significance in accurately assessing severity and guiding targeted preventative interventions.

A mixed-methods study to evaluate the feasibility and preliminary efficacy of delivering the optimal health program (OHP) for youth at clinical high risk (CHR) for psychosis: A study protocol.

Individuals with clinical high risk (CHR) for psychosis experience significant distress, impaired general functioning and a high lifetime risk of self-harm and attempted suicide. The CHR period is an important phase in an individual's mental health where appropriate interventions may reduce the risk of progression to several negative outcomes, including the development of schizophrenia. Given that up to 80% of individuals with CHR have another diagnosable mental illness and almost half experience poor psychosocial functioning, developing interventions that address psychosocial functioning in young people with CHR is of great importance. This mixed-methods study aims to employ qualitative and quantitative methods to adapt an evidence-based comprehensive psychosocial and mental health self-efficacy program, the Optimal Health Program (OHP), and evaluate the feasibility, acceptability and preliminary clinical efficacy in young people with CHR. We aim to recruit 30 CHR participants (age 16-29 years) in a single-arm 12-week exploratory clinical trial. Feasibility metrics will include recruitment, retention, and data completion rates. Acceptability will be informed by the Client Satisfaction Questionnaire. Clinical assessments (psychosis spectrum symptoms, depression, and anxiety), functional measures, and cognitive outcomes will be completed at study entry and repeated post-intervention at 12-weeks. We will run pre-post test data analysis to examine changes following engagement in the OHP intervention. Qualitative interviews will be conducted post-intervention to further evaluate the acceptability of the intervention and the trial design, and will be analyzed using thematic analysis. OHP may enhance the long-term mental health, well-being and functioning of CHR youth. However, the intervention must first be adapted to a CHR population; then, the feasibility and preliminary efficacy of delivering an intervention tailored around the varied needs of the CHR group must be established before a larger-scale appropriately powered study is pursued. Trial registration: The trial is registered with ClinicalTrials.gov NCT05757128.

Basic symptoms in young female patients with depression within the framework of schizophrenia and affective spectrum disorders

To investigate the structure and severity of basic symptoms in young female patients with endogenous depression. One hundred and nineteen female patients, aged from 16 to 26 years, were examined. Three groups were identified: patients meeting the criteria of high risk of psychosis (51 patients, mean age 18.55±3.84 years), patients not meeting the criteria of high risk of psychosis(48 patients, mean age 20.12±3.84 years), patients with postpsychotic depression (20 patients, mean age 21.8±4.5 years). The main method of the study was the application of COGDIS (Cognitive Distortions) and COPER (Cognitive-perceptual baseline symptoms) criteria. The baseline symptoms criteria were met by 83.3% of depressed patients without psychosis risk symptoms (mean severity score 24.0±14.7), 96% of depressed patients with high psychosis risk symptoms (38.1±15.9 points), and 50% of patients with postpsychotic depression (15.3±12.9 points). COGDIS criteria were met by 62.5% of depressed patients without psychosis risk symptoms (16.2±10.1 points), 68.6% of depressed patients with high psychosis risk symptoms (22.3±9.6 points), and 25% of patients with postpsychotic depression (9.2±8.4 points). The COPER criteria were met by 77.5% of patients with depression without psychosis risk symptoms (16.2±10.3 points), 92.2% of patients with depression at high risk of psychosis (28.4±14.0 points), and 50% of patients with postpsychotic depression (8.9±9.7 points). The group with post schizophrenic depression was characterized by lower basic symptom scale scores and percentage of eligible patients. Basic symptoms were common in a group of young female patients with depression who did not meet high-risk criteria. The score differentiates the high-risk group from the group of patients without risk symptoms.

Ultra-high risk for psychosis stigma: an updated Systematic Review.

To clarify if stigma associated with schizophrenia has also been directed towards the ultra-high risk for psychosis (UHR) population, the present review aimed at synthetizing the existing literature to update and extend our understanding on the topic. A systematic PRISMA-compliant review was performed in PubMed, Embase, Cochrane and Web of Science for articles published until 30/04/2023, using a combination of search terms describing the at-risk mental states for psychosis and stigma and correlated terms. Thirty-eight studies were included. Twenty-nine addressed UHR individuals directly, and 9 conducted interviews with non-patients regarding UHR. A total of 2560 UHR individuals were assessed; mean sample size was of 88.3 participants. Most of the studies were quantitative non-randomized/observational with young adults, 71.4% used SIPS (Structured Interview for Psychosis-risk Syndromes) and 25.0% used CAARMS (Comprehensive Assessment of At-Risk Mental States). Overall, the summarized studies have mainly involved individuals already attending UHR clinics from Western and high income countries. Studies can be grouped into five forms of stigma, among which the most frequently explored was perceived public stigma, followed by public stigma, self-stigma/internalized stigma, stigma stress and associative stigma. The main study design was quantitative nonrandomized, with only one interventional study. Most of the results confirmed the presence of stigma toward UHR individuals and findings provide additional support to the fact that stigma seems to be present since the very early stages of the disease. There is still a paucity of research and knowledge gaps about UHR-related stigma. Nevertheless, results suggest the presence of stigma toward UHR individuals, supporting the fact that stigma is present since the early stages of psychosis.

Kenya Psychosis-Risk Outcomes Study (KePROS): Development of an Accelerated Medicine Partnership Schizophrenia-Aligned Project in Africa.

The Accelerating Medicines Partnership Schizophrenia (AMP SCZ) funds a longitudinal study of 43 research sites across 5 continents to develop tools to stratify developmental trajectories of youth at clinical high risk for psychosis (CHR) and identify homogenous targets for future clinical trials. However, there are no sites in Africa, leaving a critical gap in our knowledge of clinical and biological outcomes among CHR individuals. We describe the development of the Kenya Psychosis-Risk Outcomes Study (KePROS), a 5-year NIH-funded project in Kenya designed to harmonize with AMP SCZ. The study will recruit over 100 CHR and 50 healthy participants and conduct multiple clinical and biomarker assessments over 2 years. Capacity building is a key component of the study, including the construction of an electroencephalography (EEG) laboratory and the upgrading of a local 3 T magnetic resonance imaging (MRI) machine. We detail community recruitment, study methodologies and protocols, and unique challenges with this pioneering research in Africa. This paper is descriptive only. Planned future analyses will investigate possible predictors of clinical outcomes and will be compared to results from other global populations. KePROS will provide the research community with a rich longitudinal clinical and biomarker dataset from an African country in the developing Global South, which can be used alongside AMP SCZ data to delineate CHR outcome groups for future treatment development. Training in mental health assessment and investment in cutting-edge biomarker assessment and other technologies is needed to facilitate the inclusion of African countries in large-scale research consortia.

Harmonizing early intervention strategies: scoping review of clinical high risk for psychosis and borderline personality disorder.

To map studies assessing both clinical high risk for psychosis (CHR-P) and borderline personality disorder (BPD) in clinical samples, focusing on clinical/research/preventive paradigms and proposing informed research recommendations. We conducted a PRISMA-ScR/JBI-compliant scoping review (protocol: https://osf.io/8mz7a) of primary research studies (cross-sectional/longitudinal designs) using valid measures/criteria to assess CHR-P and BPD (threshold/subthreshold) in clinical samples, reporting on CHR-P/psychotic symptoms and personality disorder(s) in the title/abstract/keywords, identified in Web of Science/PubMed/(EBSCO)PsycINFO until 23/08/2023. 33 studies were included and categorized into four themes reflecting their respective clinical/research/preventive paradigm: (i) BPD as a comorbidity in CHR-P youth (k = 20), emphasizing early detection and intervention in psychosis; (ii) attenuated psychosis syndrome (APS) as a comorbidity among BPD inpatients (k = 2), with a focus on hospitalized adolescents/young adults admitted for non-psychotic mental disorders; (iii) mixed samples (k = 7), including descriptions of early intervention services and referral pathways; (iv) transdiagnostic approaches (k = 4) highlighting "clinical high at risk mental state" (CHARMS) criteria to identify a pluripotent risk state for severe mental disorders. The scoping review reveals diverse approaches to clinical care for CHR-P and BPD, with no unified treatment strategies. Recommendations for future research should focus on: (i) exploring referral pathways across early intervention clinics to promote timely intervention; (ii) enhancing early detection strategies in innovative settings such as emergency departments; (iii) improving mental health literacy to facilitate help-seeking behaviors; (iv) analysing comorbid disorders as complex systems to better understand and target early psychopathology; (v) investigating prospective risk for BPD; (vi) developing transdiagnostic interventions; (vii) engaging youth with lived experience of comorbidity to gain insight on their subjective experience; (viii) understanding caregiver burden to craft family-focused interventions; (ix) expanding research in underrepresented regions such as Africa and Asia, and; (x) evaluating the cost-effectiveness of early interventions to determine scalability across different countries. https://osf.io/8mz7a.

Palliative care patients' attitudes and openness towards psilocybin-assisted psychotherapy for existential distress.

Patients with incurable illnesses often experience existential distress, profoundly impacting their well-being. Current medical approaches have limitations in addressing these burdens. Psilocybin, a promising psychedelic compound, may offer therapeutic benefits. This pilot survey study aimed to investigate the attitudes and openness toward psilocybin-assisted psychotherapy (PAT) among patients with incurable illnesses. The objective is to assess patients' attitudes toward PAT and identify potential barriers and concerns, including exploring the association between beliefs in psilocybin's therapeutic benefits and interest in receiving this treatment. The survey study was conducted at the Tampa General Hospital Palliative Care Outpatient office in the United States. Participants were 32 English-fluent patients, aged 18 or older, with incurable illnesses. The survey included demographic questions, a validated tool to measure existential distress, and questions about knowledge and concerns regarding psilocybin. Attitudes toward PAT and interest in its future use were assessed using Likert scale responses. Among the 31 analyzed participants, 51.6% expressed interest in future psilocybin treatment, while 32.3% did not indicate interest. Belief in the psilocybin's therapeutic benefits for stress and anxiety significantly correlated with interest in use. Concerns included risk of psychosis, lack of trained providers, and potential for exploitation. No demographic factors were associated with interest or levels of distress. This pilot study provides insights into the attitudes and concerns toward PAT among patients with incurable illnesses. Over half of participants expressed interest. However, concerns regarding its use were identified, with patients' concern for the risk of exploitation associated with PAT as an especially novel concern documented in this patient population. This highlighted the need for further education of risks and benefits or PAT by trained clinicians and rigorous training of clinicians with the establishment of safeguards against exploitation. Further research is necessary to explore the potential benefits of PAT and related non-psilocybin psychedelic compounds in addressing existential distress among patients with incurable illnesses.

Structural Features of the Brain in Juvenile Depression with Clinical High Risk of Psychosis

Structural Features of the Brain in Juvenile Depression with Clinical High Risk of Psychosis

Supplemental Material for The Hierarchical Taxonomy of Psychopathology in Clinical High Risk for Psychosis: Validation and Extension

Supplemental Material for The Hierarchical Taxonomy of Psychopathology in Clinical High Risk for Psychosis: Validation and Extension

Detection and management of patients with clinical high risk for psychosis

This article explores best practices for managing patients with Clinical High Risk for psychosis with a particular focus on the role of general practitioners and pediatricians. It offers clear guidelines for the assessment and monitoring of these patients, highlighting early warning signs, screening tools, and appropriate interventions. Additionally, the article lists local resources available for healthcare professionals to ensure optimal and coordinated care. By providing this information, this article aims to equip general practitioners and pediatricians with the necessary knowledge to effectively identify and manage this patient profile, while connecting them to the appropriate available resources.