Background:
There is a higher incidence of psychotic disorders in neighbourhoods of greater social deprivation. However, it is not known whether this represents a causal relationship, as the stage at ...which social deprivation exerts its influence on the development of psychotic disorders is yet to be elucidated. We aimed to investigate the association between neighbourhood-level social deprivation and the rate of identification of individuals at Ultra-High Risk for psychosis (UHR), as well as the risk of transition to psychosis in UHR individuals.
Methods:
The cohort included all young people aged 15 to 24 identified as UHR attending an Early Intervention clinic in northwestern Melbourne over a 5-year period (2012–2016). Australian census data were used to obtain the at-risk population and social deprivation information according to the postcode of residence. Levels of social deprivation were arranged into quartiles. Poisson regression was used to calculate rate ratios and Cox regression analysis determined hazard ratios.
Results:
Of the 461 young people identified as UHR, 11.1% (n = 49) lived in the most affluent neighbourhoods (Quartile 1) compared to 36.7% (n = 162) in the most deprived neighbourhoods (Quartile 4). There was a 35% higher rate of identification of young people who were UHR from the most deprived neighbourhoods (aIRR = 1.35, 95% CI 0.98, 1.86). Over a median follow-up of approximately 10 months (308 days (IQR: 188–557), 17.5% (n = 77) were known to have transitioned to a full-threshold psychotic disorder. Residing in a neighbourhood of above average deprivation had a hazard ratio of 2.05 (95% CI 0.88, 4.80) for risk of transition, when controlling for age, sex and substance use.
Conclusions:
These findings provide more support that EI services should be funded as per the expected incidence of psychotic disorders.
Aim
Clinical staging in psychiatry aims to classify patients according to the severity of their symptoms, from stage 0 (increased risk, asymptomatic) to stage 4 (severe illness), enabling adapted ...treatment at each stage of the illness. The staging model would gain specificity if one or more quantifiable biological markers could be identified. Several biomarkers reflecting possible causal mechanisms and/or consequences of the pathophysiology are candidates for integration into the clinical staging model of psychiatric illnesses.
Methods
This review covers the evolution (from stage 0 to stage 4) of the most important brain functioning impairments as measured with electroencephalography (EEG), in psychosis spectrum and in severe mood disorders.
Results
The present review of the literature demonstrates that it is currently not possible to draw any conclusion with regard to the state or trait character of any of the EEG impairments in both major depressive disorder and bipolar disorder. As for schizophrenia, the most promising markers of the stage of the illness are the pitch mismatch negativity as well as the p300 event‐related potentials, as these components seem to deteriorate with increasing severity of the illness.
Conclusions
Given the complexity of major psychiatric disorders, and that not a single impairment can be observed in all patients, future research should most likely consider combinations of markers in the quest for a better identification of the stages of the psychiatric illnesses.
Aims 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. Methods 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. Results 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. Conclusion 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. Systematic Review Registration https://osf.io/8mz7a .
Most psychiatric disorders develop during adolescence and young adulthood and are preceded by a phase during which attenuated or episodic symptoms and functional decline are apparent. The ...introduction of the ultra-high risk (UHR) criteria two decades ago created a new framework for identification of risk and for pre-emptive psychiatry, focusing on first episode psychosis as an outcome. Research in this paradigm demonstrated the comorbid, diffuse nature of emerging psychopathology and a high degree of developmental heterotopy, suggesting the need to adopt a broader, more agnostic approach to risk identification. Guided by the principles of clinical staging, we introduce the concept of a pluripotent at-risk mental state. The clinical high at risk mental state (CHARMS) approach broadens identification of risk beyond psychosis, encompassing multiple exit syndromes such as mania, severe depression, and personality disorder. It does not diagnostically differentiate the early stages of psychopathology, but adopts a "pluripotent" approach, allowing for overlapping and heterotypic trajectories and enabling the identification of both transdiagnostic and specific risk factors. As CHARMS is developed within the framework of clinical staging, clinical utility is maximized by acknowledging the dimensional nature of clinical phenotypes, while retaining thresholds for introducing specific interventions. Preliminary data from our ongoing CHARMS cohort study (
= 114) show that 34% of young people who completed the 12-month follow-up assessment (
= 78) transitioned from Stage 1b (attenuated syndrome) to Stage 2 (full disorder). While not without limitations, this broader risk identification approach might ultimately allow reliable, transdiagnostic identification of young people in the early stages of severe mental illness, presenting further opportunities for targeted early intervention and prevention strategies.
Objective
Youths at clinical high risk for psychosis (CHR-P) are characterized by a high prevalence of anxiety and depressive disorders. The present study aimed at developing and analyzing a network ...structure of CHR-P symptom domains (i.e., positive, negative, disorganization, and general subclinical psychotic symptoms), depressive and anxiety symptoms, and general functioning.
Methods
Network analysis was applied to data on 111 CHR-P children and adolescents (
M
age
= 14.1), who were assessed using the Structured Interview for Prodromal Syndromes, the Children’s Depression Inventory, the Children’s Global Assessment Scale, and the Multidimensional Anxiety Scale for Children.
Results
In the network, negative and disorganization symptoms showed the strongest association (
r
= 0.71), and depressive and anxiety symptoms showed dense within-domain connections, with a main bridging role played by physical symptoms of anxiety. The positive symptom cluster was not associated with any other node. The network stability coefficient (CS) was slightly below 0.25, and observed correlations observed ranged from 0.35 to 0.71.
Conclusion
The lack of association between subclinical positive symptoms and other network variables confirmed the independent nature of subclinical positive symptoms from comorbid symptoms, which were found to play a central role in the analyzed network. Complex interventions should be developed to target positive and comorbid symptoms, prioritizing those with the most significant impact on functioning and the most relevance for the young individual, through a shared decision-making process. Importantly, the results suggest that negative and disorganization symptoms, as well as depressive and anxiety symptoms, may be targeted simultaneously.
Introduction:
While the majority of young people who meet the criteria for being considered at increased risk of psychosis do not go on to develop a psychotic disorder, young people are currently ...being identified and treated in early intervention services. Ethical concerns have been raised concerning the decision about whether or not to provide treatment, and if so, what type of treatment. This study sought to support young people themselves to make these decisions with support from their clinician through a shared decision-making approach, facilitated by an online decision aid.
Methods:
This project used the International Patient Decision Aid Standards (IPDAS) to guide the development and piloting of an online decision aid across two phases: (1) qualitative, semi-structured focus groups with young people who were past clients and clinicians from an early psychosis service; and (2) pilot testing of the decision aid with clinicians and young people who were current clients to finalize the development.
Results:
Issues discussed by clinicians in the focus group were grouped into three main areas: (1) engagement phase; (2) assessment and priorities for treatment; and (3) initial and ongoing decision making. Clients focused on the context in which the decisions were made, including as they experienced initial feelings of resistance, and then acceptance of efforts made to describe and treat their mental health challenges. Clients highlighted the need for collaboration between themselves and their clinician, and the need to be equipped with the knowledge and tools to take care of themselves. These focus group data were used to refine the online decision aid. Pilot testing revealed that while it was overall useful and relevant, important limitations were noted by both clients and clinicians.
Discussion:
The use of a decision aid to facilitate shared decision making (SDM) in this area is feasible and has utility for both clients and clinicians. Use of such a tool can help to address the need to uphold the rights of young people as decision makers about their own care. Future efforts should embed decision aids within complex SDM interventions, and research to understand issues relating to implementation of these interventions.
IntroductionSchizotypal disorder is associated with a high level of disability at an individual level and high societal costs. However, clinical recommendations for the treatment of schizotypal ...disorder are scarce and based on limited evidence. This review aims to synthesise the current evidence on treatment for schizotypal disorder making recommendations for clinical practice.Methods and analysisThis systematic review protocol follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A systematic literature search will be performed in PsychArticles, Embase, Medline and Cochrane Central Register of Controlled Trials. Additionally, we will search for relevant articles manually. Inclusion criteria are published studies including individuals diagnosed with schizotypal personality disorder according to Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria, or schizotypal disorder according to International Classification of Diseases (ICD) criteria. We will include interventional studies comprising any pharmacological and non-pharmacological treatment trials for patients with schizotypal disorder, and all relevant outcome measures will be reported. Risk of bias will be assessed by Cochrane risk-of-bias tools. Data will be synthesised using narrative or thematic analysis and, if suitable, through meta-analysis.Ethics and disseminationNo original data will be collected as part of this study and ethics approval is, therefore, not applicable. The results will be disseminated through peer-reviewed publication and presented at international scientific meetings. We will aim at submitting the final paper for publication within 4 months of completion of analyses. Furthermore, this systematic review will inform clinicians and researchers on the current state of evidence on treatment for schizotypal disorder. Findings may guide proposals for further research and potentially guide recommendations for clinical practice using the Grading of Recommendations Assessment, Development and Evaluation.PROSPERO registration numberCRD42022375001.
Because increasing evidence point to the convergence of environmental and genetic risk factors to drive redox dysregulation in schizophrenia, we aim to clarify whether the metabolic anomalies ...associated with early psychosis reflect an adaptation to oxidative stress. Metabolomic profiling was performed to characterize the response to oxidative stress in fibroblasts from control individuals (n = 20) and early psychosis patients (n = 30), and in all, 282 metabolites were identified. In addition to the expected redox/antioxidant response, oxidative stress induced a decrease of lysolipid levels in fibroblasts from healthy controls that were largely muted in fibroblasts from patients. Most notably, fibroblasts from patients showed disrupted extracellular matrix- and arginine-related metabolism after oxidative stress, indicating impairments beyond the redox system. Plasma membrane and extracellular matrix, 2 regulators of neuronal activity and plasticity, appeared as particularly susceptible to oxidative stress and thus provide novel mechanistic insights for pathophysiological understanding of early stages of psychosis. Statistically, antipsychotic medication at the time of biopsy was not accounting for these anomalies in the metabolism of patients' fibroblasts, indicating that they might be intrinsic to the disease. Although these results are preliminary and should be confirmed in a larger group of patients, they nevertheless indicate that the metabolic signature of reactivity to oxidative stress may provide reliable early markers of psychosis. Developing protective measures aimed at normalizing the disrupted pathways should prevent the pathological consequences of environmental stressors.
Genetic studies have shown an association between schizophrenia and a GAG trinucleotide repeat (TNR) polymorphism in the catalytic subunit (GCLC) of the glutamate cysteine ligase (GCL), the key ...enzyme for glutathione (GSH) synthesis. The present study was aimed at analyzing the influence of a GSH dysregulation of genetic origin on plasma thiols (total cysteine, homocysteine, and cysteine-glycine) and other free amino acid levels as well as fibroblast cultures GSH levels. Plasma thiols levels were also compared between patients and controls. As compared with patients with a low-risk GCLC GAG TNR genotype, patients with a high-risk genotype, having an impaired GSH synthesis, displayed a decrease of fibroblast GSH and plasma total cysteine levels, and an increase of the oxidized form of cysteine (cystine) content. Increased levels of plasma free serine, glutamine, citrulline, and arginine were also observed in the high-risk genotype. Taken together, the high-risk genotypes were associated with a subgroup of schizophrenia characterized by altered plasma thiols and free amino acid levels that reflect a dysregulation of redox control and an increased susceptibility to oxidative stress. This altered pattern potentially contributes to the development of a biomarker profile useful for early diagnosis and monitoring the effectiveness of novel drugs targeting redox dysregulation in schizophrenia.
Aim
The ‘ultra‐high‐risk’ criteria identify a clinical population at substantially increased risk for progressing to schizophrenia and other psychotic disorders. Although a number of clinical ...variables predictive of transition to psychotic disorder have been identified within this population, the predictive value of the level of distress associated with attenuated psychotic symptoms has not yet been examined. This was the aim of the present study.
Method
The level of distress (0–100) associated with attenuated psychotic symptoms was recorded for 70 ultra‐high‐risk (UHR) patients using the Comprehensive Assessment of At‐Risk Mental State (CAARMS). Transition to psychosis was assessed over a 16‐month follow‐up period.
Results
Of the 70 UHR patients, 15 transitioned to psychosis (21.4%). Of the four CAARMS subscales measuring attenuated positive symptoms, Perceptual Abnormalities was rated as the most distressing. There were no differences in CAARMS scales rated as the most distressing between those who transitioned to psychosis and those who did not. There was also no association between higher levels of distress associated with attenuated psychotic symptoms and transition to psychosis.
Conclusion
Although the findings require replication, they indicate that the degree of distress associated with attenuated psychotic symptoms should not be used as a criterion for enriching UHR samples for risk of frank psychotic disorder.
PDF
