Search

Aim: Basic self disturbance is a putative core vulnerability marker of schizophrenia spectrum disorders. The primary aims of the Self, Neuroscience and Psychosis (SNAP) study are to: (1) empirically test a previously described neurophenomenological self‐disturbance model of psychosis by examining the relationship between specific clinical, neurocognitive, and neurophysiological variables in UHR patients, and (2) develop a prediction model using these neurophenomenological disturbances for persistence or deterioration of UHR symptoms at 12‐month follow‐up. Methods: SNAP is a longitudinal observational study. Participants include 400 UHR individuals, 100 clinical controls with no attenuated psychotic symptoms, and 50 healthy controls. All participants complete baseline clinical and neurocognitive assessments and electroencephalography. The UHR sample are followed up for a total of 24 months, with clinical assessment completed every 6 months. Results: This paper presents the protocol of the SNAP study, including background rationale, aims and hypotheses, design, and assessment procedures. Conclusions: The SNAP study will test whether neurophenomenological disturbances associated with basic self‐disturbance predict persistence or intensification of UHR symptomatology over a 2‐year follow up period, and how specific these disturbances are to a clinical population with attenuated psychotic symptoms. This may ultimately inform clinical care and pathoaetiological models of psychosis. [ABSTRACT FROM AUTHOR]

Key Points: Question: What are the optimal type, timing, and sequence of interventions for individuals at ultrahigh risk of psychosis? Findings: In this sequential multiple assignment randomized trial including 342 individuals, a specialized psychological intervention (cognitive-behavioral case management [CBCM]) and a psychopharmacological intervention (CBCM and antidepressant medication) were not more efficacious than control conditions in improving remission and functional recovery. Relapse rates among individuals who remitted were high. Meaning: The findings of this study show that addition of sequentially more specialized psychosocial and antidepressant treatment for individuals who did not remit did not lead to superior outcomes, underscoring the need for further adaptive trials, treatment innovation, and an extended duration of care for relapse prevention. This sequential multiple assignment randomized trial evaluates the efficacy of an intervention strategy for individuals at ultrahigh risk of psychosis. Importance: Clinical trials have not established the optimal type, sequence, and duration of interventions for people at ultrahigh risk of psychosis. Objective: To determine the effectiveness of a sequential and adaptive intervention strategy for individuals at ultrahigh risk of psychosis. Design, Setting, and Participants: The Staged Treatment in Early Psychosis (STEP) sequential multiple assignment randomized trial took place within the clinical program at Orygen, Melbourne, Australia. Individuals aged 12 to 25 years who were seeking treatment and met criteria for ultrahigh risk of psychosis according to the Comprehensive Assessment of At-Risk Mental States were recruited between April 2016 and January 2019. Of 1343 individuals considered, 342 were recruited. Interventions: Step 1: 6 weeks of support and problem solving (SPS); step 2: 20 weeks of cognitive-behavioral case management (CBCM) vs SPS; and step 3: 26 weeks of CBCM with fluoxetine vs CBCM with placebo with an embedded fast-fail option of ω-3 fatty acids or low-dose antipsychotic medication. Individuals who did not remit progressed through these steps; those who remitted received SPS or monitoring for up to 12 months. Main Outcomes and Measures: Global Functioning: Social and Role scales (primary outcome), Brief Psychiatric Rating Scale, Scale for the Assessment of Negative Symptoms, Montgomery-Åsberg Depression Rating Scale, quality of life, transition to psychosis, and remission and relapse rates. Results: The sample comprised 342 participants (198 female; mean [SD] age, 17.7 [3.1] years). Remission rates, reflecting sustained symptomatic and functional improvement, were 8.5%, 10.3%, and 11.4% at steps 1, 2, and 3, respectively. A total of 27.2% met remission criteria at any step. Relapse rates among those who remitted did not significantly differ between SPS and monitoring (step 1: 65.1% vs 58.3%; step 2: 37.7% vs 47.5%). There was no significant difference in functioning, symptoms, and transition rates between SPS and CBCM and between CBCM with fluoxetine and CBCM with placebo. Twelve-month transition rates to psychosis were 13.5% (entire sample), 3.3% (those who ever remitted), and 17.4% (those with no remission). Conclusions and Relevance: In this sequential multiple assignment randomized trial, transition rates to psychosis were moderate, and remission rates were lower than expected, partly reflecting the ambitious criteria set and challenges with real-world treatment fidelity and adherence. While all groups showed mild to moderate functional and symptomatic improvement, this was typically short of remission. While further adaptive trials that address these challenges are needed, findings confirm substantial and sustained morbidity and reveal relatively poor responsiveness to existing treatments. Trial Registration: ClinicalTrials.gov Identifier: NCT02751632 [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 CHRP 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 (Mage = 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. [ABSTRACT FROM AUTHOR]

Objective: Language used in psychiatry is important because it provides an understandable and accurate way of describing clinical and theoretical concepts. The use of labels in psychiatry has often been associated with stigma and reduced engagement with clinical services. This studys aims were to generate new terms for the 'at-risk mental state' (ARMS) concept and to investigate what young people, their caregivers and clinicians thought about them as well as terms commonly used in early intervention clinics. Another aim was to understand participants preference related to the best timing to introduce the at-risk concept and the extent and context of the information presented.Methods: New terms illustrating the at-risk concept have been generated by a youth reference group with lived experience of mental illness: 'pre-diagnosis stage' (PDS), potential of developing a mental illness (PDMI) and disposition for developing a mental illness (DDMI). A specifically designed questionnaire was administered to 46 patients with ARMS, 24 caregivers and 52 clinicians to obtain their feedback on newly proposed terms and on the terms already used in clinical practice and research.Results: The preferred terms were PDS, PDMI and ARMS. The least favoured terms were Ultra High Risk and Attenuated Psychosis Syndrome, which were thought to be associated with the most stigma. Most participants agreed that disclosure about diagnosis should be delivered early by the key clinician.Conclusions: Patients generated terms such as PDS, PDMI, alongside ARMS should be considered to be used in clinical practice. They present with low stigma and are illustrative of young peoples difficulties. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aim: Several prediction models have been introduced to identify young people at greatest risk of transitioning to psychosis. To date, none has examined the possibility of developing a clinical prediction model of outcomes other than transition. The aims of this study were to examine the association between baseline clinical predictors and outcomes including, but not limited to, transition to psychosis in young people at risk for psychosis, and to develop a prediction model for these outcomes. Methods: Several evidence‐based variables previously associated with transition to psychosis and some important clinical comorbidities experienced by ultra‐high risk (UHR) individuals were identified in 202 UHR individuals. Secondary analysis of the Neurapro clinical trial were conducted to investigate the associations between these variables and favourable (remission and recovery) or unfavourable (transition to psychosis, no remission, any recurrence and relapse) clinical outcomes. Logistic regression, best subset selection, Akaike Information Criterion and receiver operating characteristic curves were used to seek the best prediction model for clinical outcomes from all combinations of possible predictors. Results: When considered individually, only higher general psychopathology levels (P =.023) was associated with the unfavourable outcomes. Prediction models suggest that general psychopathology and functioning are predictive of unfavourable outcomes. Conclusion: The predictive performance of the resulting models was modest and further research is needed. Nonetheless, when designing early intervention centres aiming to support individuals in the early phases of a mental disorder, the proper assessment of general psychopathology and functioning should be considered in order to inform interventions and length of care provided. [ABSTRACT FROM AUTHOR]

Antipsychotic medication has been the mainstay of treatment for psychotic illnesses for over 60 years. This has been associated with improvements in positive psychotic symptoms and a reduction in relapse rates. However, there has been little improvement in functional outcomes for people with psychosis. At the same time there is increasing evidence that medications contribute to life shortening metabolic and cardiovascular illnesses. There is also uncertainty as to the role played by antipsychotic medication in brain volume changes. Aim: The primary aim of the study is, in a population of young people with first‐episode psychosis, to compare functional outcomes between an antipsychotic dose reduction strategy with evidence‐based intensive recovery treatment (EBIRT) group (DRS+) and an antipsychotic maintenance treatment with EBIRT group (AMTx+) at 24‐months follow‐up. Methods: Our single‐blind randomized controlled trial, within a specialist early psychosis treatment setting, will test the whether the DRS+ group leads to better vocational and social recovery than, the AMTx+ group over a 2‐year period in 180 remitted first‐episode psychosis patients. Additionally, we will examine the effect of DRS+ vs AMTx+ on physical health, brain volume and cognitive functioning. This study will also determine whether the group receiving DRS+ will be no worse off in terms of psychotic relapses over 2 years follow‐up. Results: This paper presents the protocol, rationale and hypotheses for this study which commenced recruitment in July 2017. Conclusion: This study will provide evidence as to whether an antipsychotic dose‐reduction recovery treatment leads to improved functioning and safer outcomes in first‐episode psychosis patients. In addition, it will be the first‐controlled experiment of the effect of exposure to antipsychotic maintenance treatment on brain volume changes in this population. [ABSTRACT FROM AUTHOR]

Aim: It is now necessary to investigate whether recovery in psychosis is possible without the use of antipsychotic medication. This study will determine (1) whether a first‐episode psychosis (FEP) group receiving intensive psychosocial interventions alone can achieve symptomatic remission and functional recovery; (2) whether prolonging the duration of untreated psychosis (DUP) in a sub‐group according to randomisation will be associated with a poorer outcome and thereby establish whether the relationship between DUP and outcome is causative; and (3) whether neurobiological changes observed in FEP are associated with the psychotic disorder or antipsychotic medication. Baseline characteristics of participants will be presented. Methods: This study is a triple‐blind randomized placebo‐controlled non‐inferiority trial. The primary outcome is the level of functioning measured by the Social and Occupational Functioning Assessment Scale at 6 months. This study is being conducted at the Early Psychosis Prevention and Intervention Centre, Melbourne and includes young people aged 15 to 24 years with a DSM‐IV psychotic disorder, a DUP less than 6 months and not high risk for suicide or harm to others. Strict discontinuation criteria are being applied. Participants are also undergoing three 3‐Tesla‐MRI scans. Results: Ninety participants have been recruited and baseline characteristics are presented. Conclusions: Staged treatment and acceptability guidelines in early psychosis will determine whether antipsychotic medications are indicated in all young people with a FEP and whether antipsychotic medication can be safely delayed. Furthermore, the relative contribution of psychotic illness and antipsychotic medication in terms of structural brain changes will also be elucidated. The findings will inform clinical practice guidelines. [ABSTRACT FROM AUTHOR]

Aim: To examine reasons for referral to a specialist ultra‐high risk (UHR) for psychosis clinic and whether these reasons are associated with risk for subsequent transition to psychosis. Methods: Data for 127 patients referred to the Personal Assessment and Crisis Evaluation clinic were collected by medical record audit. Time to transition to psychosis was calculated from date of referral to time at which the young person was judged by their treating team to be experiencing onset of first episode psychosis. Results: Patients were primarily referred due to attenuated psychotic symptoms and depression (40.2%). There was an association with transition, with those in the attenuated psychotic‐symptom‐only category being more likely to transition. Conclusion: As well as attenuated psychotic symptoms, depression and anxiety were also important reasons for referral indicating that there is a broad clinical phenotype of young people presenting to UHR clinics. Clinical reason for referral may index level of risk for subsequent transition to psychosis. [ABSTRACT FROM AUTHOR]

Background: Traditionally, research in the ultra-high risk (UHR) for psychosis population has focused on the treatment of existing symptomatology and prevention of transition to psychosis. Recently, there has been an increase in focus on outcomes in individuals who do not transition to psychosis. However, there is a lack of standardised definitions of remission, recovery, recurrence and relapse in UHR, resulting in the inability to generalise and replicate outcomes.Method: The aims of the current study were to develop definitions for remission, recovery, recurrence and relapse, and apply them to a UHR cohort allowing the identification of longitudinal clinical trajectories. Further stratification in broader categories of favourable and unfavourable outcomes was applied. The predictive value of various baseline factors on specific clinical trajectories was also assessed.Results: 17 different trajectories were identified in a cohort of 202 individuals within a 12-month period and classified according to the suggested definitions for recovery (35.7%), remission (7.5%), any recurrence (20%), no remission (17.3%), relapse (4.0%) and transition to psychosis (15.8%). Favourable and unfavourable trajectories represented 43.2% and 57.1% respectively. Long duration of untreated symptoms and high depression scores were associated with unfavourable outcomes.Discussion: It is possible to apply clear definitions of remission, recovery, recurrence, relapse and transition to psychosis to a UHR cohort to evaluate longitudinal clinical trajectories. Acceptance and use of these definitions will help to facilitate comparisons between trials and to improve clinical clarity across the range of available therapeutic options in UHR individuals. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aim: Duration of untreated psychosis (DUP) refers to the time elapsing between psychosis onset and treatment initiation. Despite a certain degree of consensus regarding the definition of psychosis onset, the definition of treatment commencement varies greatly between studies and DUP may be underestimated due to lack of agreement. In the present study, three sets of criteria to define the end of the untreated period were applied in a first-episode psychosis cohort to assess the impact of the choice of definition on DUP estimation. Methods: The DUP of 117 patients admitted in the Treatment and Early Intervention in Psychosis Program Psychosis in Lausanne was measured using the following sets of criteria to define treatment onset: (i) initiation of antipsychotic medication; (ii) entry into a specialized programme; and (iii) entry into a specialized programme and adequate medication with a good compliance. Results: DUP varied greatly according to definitions, the most restrictive criteria leading to the longest DUP (median DUP1 = 2.2 months, DUP2 = 7.4 months and DUP3 = 13.6 months). A percentage of 19.7 of the patients who did not meet these restrictive criteria had poorer premorbid functioning and were more likely to use cannabis. Longer DUP3 was associated with poorer premorbid functioning and with younger age at onset of psychosis. Conclusion: These results underline the need for a unique and standardized definition of the end of DUP. We suggest that the most restrictive definition of treatment should be used when using the DUP concept in future research. [ABSTRACT FROM AUTHOR]

Labeling terms for high-risk state for psychosis, such as 'ultra-high risk' (UHR), 'attenuated psychosis syndrome' (APS), and 'at-risk mental state' (ARMS), have been criticized for their potential to lead to stigma. Hence, mental health service users in Melbourne recently proposed new terms illustrating the at-risk concept ['pre-diagnosis stage' (PDS), 'potential of developing a mental illness' (PDMI), and 'disposition for developing a mental illness' (DDMI)]. We aimed at testing the suitability of these existing and new terms in the clinical settings of early psychiatric intervention in Japan. At two centers of early intervention (Toyama and Tokyo), a questionnaire on the understanding and opinion of high-risk terminology was administered to 62 high-risk patients, 44 caregivers, and 64 clinicians. The questionnaire contained the existing and new terms, where the term ARMS was translated into two different Japanese terms ARMS-psychosis and ARMS- kokoro. Participants' opinion on the disclosure of high-risk status was also obtained. ARMS- kokoro was most preferred, least stigmatizing, and best explaining the patients' difficulties for all groups, while UHR and other terms including the Japanese word 'psychosis' (i.e., APS and ARMS-psychosis) were not preferred. New labeling terms were generally not well received. All groups preferred full disclosure of high-risk terms by the psychiatrist with or without the presence of family members. The term ARMS- kokoro was commonly accepted as a favorable labeling term for the high-risk state for psychosis in Japan. However, another translation ARMS-psychosis was considered stigmatizing, demonstrating the importance of appropriate translation of high-risk terminology into local languages. • Existing terms for psychosis high-risk status may lead to stigma. • Patients, family members, and clinicians were surveyed about high-risk terms. • ARMS- kokoro was most preferred and least stigmatizing among high-risk terms. • Ultra-high risk and other terms including 'psychosis' were not preferred. [ABSTRACT FROM AUTHOR]

The article focuses on the development of psychoeducation interventions to explain illness and treatment to patients with first-episode psychosis (FEP). These interventions are conducted in group, individual, or multifamily group formats to discuss the illness from a multidimensional viewpoint. Psychoeducational program used in a hospital unit specializing in the acute treatment of FEP patients comprises of four modules, including psychotic symptoms, cannabis and psychosis, psychosis and medication, and psychosis and recovery.

The article discusses the results of studies on the relationship between duration of untreated psychosis (DUP) and outcome. Imaging data indicate that if there is an active process of neuroprogression underlying active and progressive structural change in key brain areas such as the hippocampus, then the longer the DUP, the greater the time available for the potentially neurotoxic process to unfold.

Decreased brain activity in the frontal region, as indicated by increased slow wave EEG power measured by electrodes place on the skull over this area, in association with negative symptoms has previously been shown to distinguish ultra-high risk (UHR) individuals who later transitioned to psychosis (UHR-P) from those who did not transition (UHR-NP). The aims of the current study were to: 1) replicate these results and 2) investigate whether similar association between increased frontal slow wave activity and functioning shows any value in the prediction of transition to psychosis in UHR individuals. The brain activity, recorded using EEG, of 44 UHR individuals and 38 healthy controls was included in the analyses. Symptom severity was assessed in UHR participants and functioning was measured in both groups. The power in the theta frequency band in the frontal region of UHR individuals was higher than in controls. However, there was no difference between the UHR-P and the UHR-NP groups, and no change in slow frequency power following transition to psychosis. The correlation between delta frequency power and negative symptoms previously observed was not present in our UHR cohort, and there was no association between frontal delta or theta and functioning in either group. Increased delta power was rather correlated with depressive symptoms in the UHR group. Future research will be needed to better understand when, in the course of the illness, does the slow wave activity in the frontal area becomes impaired. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM PUBLISHER]

Inclusion of 'attenuated psychosis syndrome (APS)' in the DSM-5 has been hotly debated because of the concern about stigmatising young patients with a 'psychosis risk' label. This study aimed to investigate whether current labeling terms such as 'at risk mental state', 'ultra-high risk' (UHR) and 'APS' are suitable for people who are at risk of psychosis. This study included 105 subjects (55 patients aged 15-25years who used an early interventional service to prevent psychosis and 50 professionals who worked with them). A questionnaire regarding their opinions about the stigma associated with the above labels and the Mental Health Consumers' Experience of Stigma scale were administered. The patients were less likely than the professionals to agree that there was stigma associated with the terms 'UHR' and 'APS'. Significantly more patients with a family history of psychosis and those who had transitioned to psychosis agreed that there was stigma associated with the term 'UHR' and/or that this term should be changed. Patients who agreed with the negative attitude items for the three labeling terms and the need to change the terms 'UHR' and 'schizophrenia' showed significantly higher scores on the Stigma scale. In conclusion, patients at risk of psychosis may experience less stigma related to labels than expected by professionals, suggesting that mental health professionals may not be able to help patients unless they listen to their views on nosological and treatment issues rather than make assumptions. Previous stigmatising experiences may have strengthened the stigma attached to this label. [ABSTRACT FROM AUTHOR]

Introduction: The distinction between the schizophrenia spectrum and other types of disorders may be clinically relevant in terms of its predictive validity as suggested by studies showing schizophrenia spectrum patients have more unfavourable outcomes compared to other psychotic disorders. The present study aimed to investigate whether basic self-disturbances and neurocognitive processes that have been linked to psychosis risk have discriminative power for schizophrenia spectrum disorders in patients presenting with first episode psychosis (FEP) and at ultra-high risk for psychosis (UHR).Methods: 38 FEP patients, 48 UHR patients, and 33 healthy controls were assessed for basic self-disturbances (using the Examination of Anomalous Self-Experience, EASE, interview), source monitoring and aberrant salience (behavioural tasks to measure neurocognitive constructs). Clinical groups were divided into patients with schizophrenia spectrum disorders and those with other non-spectrum disorders and were further compared on measures controlling for symptom severity and age.Results: Basic self-disturbances distinguished schizophrenia spectrum from non-spectrum disorders in the 'FEP only' sample, F = 19.76, p < 0.001, η2partial = 0.37, and also in the combined UHR/FEP sample, F = 23.56, p < 0.001, η2partial = 0.22. Additionally, some processes related to source monitoring deficits were elevated in schizophrenia spectrum disorders. In contrast, the two groups (schizophrenia spectrum vs other diagnoses) performed similarly in aberrant salience tasks. Comparable results were obtained for analyses performed with an FEP/UHR combined sample and the 'FEP only' sample.Discussion: Basic self-disturbances at the phenomenological level and source monitoring deficits on the neurocognitive level may be useful in identifying risk of schizophrenia spectrum disorders at the earliest clinical presentation. [ABSTRACT FROM AUTHOR]

Considerable research has been conducted seeking risk factors and constructing prediction models for transition to psychosis in individuals at ultra-high risk (UHR). Nearly all such research has only employed baseline predictors, i.e. data collected at the baseline time point, even though longitudinal data on relevant measures such as psychopathology have often been collected at various time points. Dynamic prediction, which is the updating of prediction at a post-baseline assessment using baseline and longitudinal data accumulated up to that assessment, has not been utilized in the UHR context. This study explored the use of dynamic prediction and determined if it could enhance the prediction of frank psychosis onset in UHR individuals. An emerging statistical methodology called joint modelling was used to implement the dynamic prediction. Data from the NEURAPRO study (n = 304 UHR individuals), an intervention study with transition to psychosis study as the primary outcome, were used to investigate dynamic predictors. Compared with the conventional approach of using only baseline predictors, dynamic prediction using joint modelling showed significantly better sensitivity, specificity and likelihood ratios. As dynamic prediction can provide an up-to-date prediction for each individual at each new assessment post entry, it can be a useful tool to help clinicians adjust their prognostic judgements based on the unfolding clinical symptomatology of the patients. This study has shown that a dynamic approach to psychosis prediction using joint modelling has the potential to aid clinicians in making decisions about the provision of timely and personalized treatment to patients concerned. [ABSTRACT FROM AUTHOR]

Background: There is evidence to suggest that people with established psychotic disorders show impairments in the mismatch negativity induced by a frequency-deviant sound (fMMN), and that these impairments worsen with the deterioration of psychotic symptoms. This study aimed to test whether individuals at ultra-high risk (UHR) for psychosis show pre-morbid impairments in fMMN, and if so, whether fMMN continues to deteriorate with transition to psychosis.Method: fMMN was recorded in a cohort of UHR individuals (n=42) and compared to healthy controls (n=29). Of the 27 UHR participants who returned for a second EEG session, six participants had transitioned to psychosis by 12-month follow-up (UHR-T) and were compared to the 21 participants who did not transition (UHR-NT).Results: fMMN amplitude was significantly reduced, relative to healthy controls, in the UHR cohort. Furthermore, UHR-T individuals showed a significant decrease in fMMN amplitude over the period from baseline to post-transition; this reduction was not observed in UHR-NT.Conclusions: These results suggest that fMMN is abnormal in UHR individuals, as has repeatedly been found previously in people with established psychotic disorders. The finding that fMMN impairment worsens with transition to psychosis is consistent with the staging model of psychosis; however, caution must be taken in interpreting these findings, given the extremely small sample size of the UHR-T group. [ABSTRACT FROM AUTHOR]

Background While reduction of DUP (Duration of Untreated Psychosis) is a key goal in early intervention strategies, the predictive value of DUP on outcome has been questioned. We planned this study in order to explore the impact of three different definition of “treatment initiation” on the predictive value of DUP on outcome in an early psychosis sample. Methods 221 early psychosis patients aged 18–35 were followed-up prospectively over 36 months. DUP was measured using three definitions for treatment onset: Initiation of antipsychotic medication (DUP1); engagement in a specialized programme (DUP2) and combination of engagement in a specialized programme and adherence to medication (DUP3). Results 10% of patients never reached criteria for DUP3 and therefore were never adequately treated over the 36-month period of care. While DUP1 and DUP2 had a limited predictive value on outcome, DUP3, based on a more restrictive definition for treatment onset, was a better predictor of positive and negative symptoms, as well as functional outcome at 12, 24 and 36 months. Globally, DUP3 explained 2 to 5 times more of the variance than DUP1 and DUP2, with effect sizes falling in the medium range according to Cohen. Conclusions The limited predictive value of DUP on outcome in previous studies may be linked to problems of definitions that do not take adherence to treatment into account. While they need replication, our results suggest effort to reduce DUP should continue and aim both at early detection and development of engagement strategies. [ABSTRACT FROM AUTHOR]

• A core feature of schizophrenia may be disturbed self-experience. • The neural underpinnings of disturbed self-experience are not yet clear. • This study found a relationship between source monitoring deficits and disturbed self-experience in early psychosis patients. • Aberrant salience showed a relationship with general psychopathology. • A revised neurophenomenological model of schizophrenia spectrum disorders is proposed. The integration of various domains or levels of analysis (clinical, neurobiological, genetic, etc.) has been a challenge in schizophrenia research. A promising approach is to use the core phenomenological features of the disorder as an organising principle for other levels of analysis. Minimal self-disturbance (fragility in implicit first-person perspective, presence and agency) is emerging as a strong candidate to play this role. This approach was adopted in a previously described theoretical neurophenomenological model that proposed that source monitoring deficits and aberrant salience may be neurocognitive/neurobiological processes that correlate with minimal self-disturbance on the phenomenological level, together playing an aetiological role in the onset of schizophrenia spectrum disorders. The current paper presents full cross-sectional data from the first empirical test of this model. Fifty ultra-high risk for psychosis patients, 39 first episode psychosis patients and 34 healthy controls were assessed with a variety of clinical measures, including the Examination of Anomalous Self-Experience (EASE), and neurocognitive and neurophysiological (EEG) measures of source monitoring deficits and aberrant salience. Linear regression indicated that source monitoring (composite score across neurocognitive and neurophysiological measures), with study group as an interaction term, explained 39.8% of the variance in EASE scores (R2 = 0.41, F(3,85) = 14.78, p < 0.001), whereas aberrant salience (composite score) explained only 6% of the variance in EASE scores (R2 = 0.06, F(3,85) = 1.44, p = 0.93). Aberrant salience measures were more strongly related to general psychopathology measures, particularly to positive psychotic symptoms, than to EASE scores. A neurophenomenological model of minimal self-disturbance in schizophrenia spectrum disorders may need to be expanded from source monitoring deficits to encompass other relevant constructs such as temporal processing, intermodal/multisensory integration, and hierarchical predictive processing. The cross-sectional data reported here will be expanded with longitudinal analysis in subsequent reports. These data and other related recent research show an emerging picture of neuro-features of core phenomenological aspects of schizophrenia spectrum disorders beyond surface-level psychotic symptoms. [ABSTRACT FROM AUTHOR]

The Ultra-High Risk (UHR) for psychosis group is known to be heterogeneous with diverse outcomes. This study aimed to: 1. Identify subclasses of UHR individuals based on trajectories of symptomatic and functional change over time, 2. Identify predictors of these trajectories. A sample of 304 UHR individuals participating in the Neurapro trial were followed over an average of 40 months. All participants received cognitive-behavioural case management (CBCM). Symptomatic and functional profiles were investigated using latent class growth analysis. Multinomial regression was employed to investigate predictors of classes. Identified trajectories showed mostly parallel slopes (i.e. improving symptoms/functioning over time), which were primarily distinct regarding the severity of symptomatology/level of functioning at baseline (i.e. the intercept). Higher symptomatic/lower functioning classes were predicted by higher substance use, older age, female gender, and lower cognitive functioning. No divergent trajectories were identified as all classes improved over time. This may reflect effective treatment through CBCM, natural illness course, or effective engagement with mental health services. Nonetheless, classes highest in symptoms/lowest in functioning still showed considerable impairment during follow-up, highlighting the need for targeted intervention in these subgroups. The study emphasizes the need for more clinical attention directed towards UHR patients being female or using substances. • In 304 individuals at risk for psychosis, different trajectories were identified. • All trajectories showed symptomatic and functional improvements over time. • Subgroups with similar trajectories differed in severity of impairments at baseline. • Substance use predicted severe risk, depressive and general symptom trajectories. • Further predictors were being female, older age, and lower cognitive functioning. [ABSTRACT FROM AUTHOR]