Limited Intermittent Psychotic Symptoms Research Articles

Adapting the early recognition inventory ERIraos to Estonian: A validation study.

Validated assessment tools are needed to identify clinically high risk for psychosis. This study aimed to validate the early recognition inventory ERIraos, which consists of the ERIraos Checklist for risk screening and the ERIraos Symptom List for a more thorough risk assessment in the Estonian language to detect psychotic prodromal symptoms. A prospective cohort study provided an opportunity to evaluate the characteristics of the ERIraos instrument in predicting the increased risk of a psychotic disorder in the future. The 177 study participants, aged 13-42 years old, were divided into groups without an increased risk and three risk groups with different risk severity levels based on the ERIraos Symptom List assessment. The results indicated excellent inter-rater reliability for the ERIraos Symptom List total score. The ability of the ERIraos checklist to screen persons with an elevated psychosis risk was very good (ROC-AUC = 0.86). The capability of the ERIraos Symptom List scores to predict the probability of transitioning to psychosis within 2 years was very good (ROC-AUC = 0.83). Brief limited intermittent psychotic symptoms and observable behavioural and affective symptoms were statistically significant predictors of transition to psychosis. There were strong and statistically significant correlations between the ERIraos Symptom List scores and other clinical measures assessing functioning and psychopathology. The results of this study demonstrate the reliability and validity of the Estonian version of the ERIraos instrument and support the usability of ERIraos as a two-step tool for the early recognition of psychosis risk.

Cognitive-behavioral therapy in ultra high risk states of psychosis (UHR)

Ultra-high risk of psychosis (UHR) is a condition associated with a higher risk of developing schizophrenia or another psychotic disorder as compared to the general population. Three groups of symptoms are reported to be related to UHR states: attenuated psychotic symptoms (APS), brief limited intermittent psychotic symptoms (BLIPS) and genetic risk and deterioration syndrome (GDR). In addition, specific cognitive deficits within attention, verbal and visual memory, executive functions and processing speed are all described as linked to UHR. UHR individuals also manifest negative cognitive beliefs and attribution biases, which affect their everyday lives. Hence, a first-line treatment recommended in UHR states is cognitive-behavioral therapy (CBT), whose effectiveness has been assessed across different studies. In this paper we describe the characteristics of UHR states, including specific cognitive difficulties they are linked with, alongside therapeutic recommendations and specificity of dedicated cognitive-behavioral treatment options.

Parsing neurobiological heterogeneity of the clinical high-risk state for psychosis: A pseudo-continuous arterial spin labelling study.

The impact of the clinical high-risk for psychosis (CHR-P) construct is dependent on accurately predicting outcomes. Individuals with brief limited intermittent psychotic symptoms (BLIPS) have higher risk of developing a first episode of psychosis (FEP) compared to individuals with attenuated psychotic symptoms (APS). Supplementing subgroup stratification with information from candidate biomarkers based on neurobiological parameters, such as resting-state, regional cerebral blood flow (rCBF), may help refine risk estimates. Based on previous evidence, we hypothesized that individuals with BLIPS would exhibit increased rCBF compared to APS in key regions linked to dopaminergic pathways. Data from four studies were combined using ComBat (to account for between-study differences) to analyse rCBF in 150 age- and sex-matched subjects (n = 30 healthy controls [HCs], n = 80 APS, n = 20 BLIPS and n = 20 FEP). Global gray matter (GM) rCBF was examined in addition to region-of-interest (ROI) analyses in bilateral/left/right frontal cortex, hippocampus and striatum. Group differences were assessed using general linear models: (i) alone; (ii) with global GM rCBF as a covariate; (iii) with global GM rCBF and smoking status as covariates. Significance was set at p < 0.05. Whole-brain voxel-wise analyses and Bayesian ROI analyses were also conducted. No significant group differences were found in global [F(3,143) = 1,41, p = 0.24], bilateral frontal cortex [F(3,143) = 1.01, p = 0.39], hippocampus [F(3,143) = 0.63, p = 0.60] or striatum [F(3,143) = 0.52, p = 0.57] rCBF. Similar null findings were observed in lateralized ROIs (p > 0.05). All results were robust to addition of covariates (p > 0.05). No significant clusters were identified in whole-brain voxel-wise analyses (p > 0.05FWE). Weak-to-moderate evidence was found for an absence of rCBF differences between APS and BLIPS in Bayesian ROI analyses. On this evidence, APS and BLIPS are unlikely to be neurobiologically distinct. Due to this and the weak-to-moderate evidence for the null hypothesis, future research should investigate larger samples of APS and BLIPS through collaboration across large-scale international consortia.

Bridging the phenomenological gap between predictive basic-symptoms and attenuated positive symptoms: a cross-sectional network analysis

Attenuated positive symptoms (APS), transient psychotic-like symptoms (brief, limited intermittent psychotic symptoms, BLIPS), and predictive cognitive-perceptive basic-symptoms (BS) criteria can help identify a help-seeking population of young people at clinical high-risk of a first episode psychosis (CHRp). Phenomenological, there are substantial differences between BS and APS or BLIPS. BS do not feature psychotic content as delusion or hallucinations, and reality testing is preserved. One fundamental problem in the psychopathology of CHRp is to understand how the non-psychotic BS are related to APS. To explore the interrelationship of APS and predictive BS, we fitted a network analysis to a dataset of 231 patients at CHRp, aged 24.4 years (SD = 5.3) with 65% male. Particular emphasis was placed on points of interaction (bridge symptoms) between the two criteria sets. The BS ‘unstable ideas of reference’ and “inability to discriminate between imagination and reality” interacted with attenuated delusional ideation. Perceptual BS were linked to perceptual APS. Albeit central for the network, predictive cognitive basic BS were relatively isolated from APS. Our analysis provides empirical support for existing theoretical accounts that interaction between the distinct phenomenological domains of BS and APS is characterized by impairments in source monitoring and perspective-taking. Identifying bridge symptoms between the symptom domains holds the potential to empirically advance the etiological understanding of psychosis and pave the way for tailored clinical interventions.

Probability of Transition to Psychosis in Individuals at Clinical High Risk

Estimating the current likelihood of transitioning from a clinical high risk for psychosis (CHR-P) to psychosis holds paramount importance for preventive care and applied research. To quantitatively examine the consistency and magnitude of transition risk to psychosis in individuals at CHR-P. PubMed and Web of Science databases until November 1, 2020. Manual search of references from previous articles. Longitudinal studies reporting transition risks in individuals at CHR-P. Meta-analysis compliant with Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guidelines; independent data extraction, manually and through digitalization of Kaplan-Meier curves. Primary effect size was cumulative risk of transition to psychosis at 0.5, 1, 1.5, 2, 2.5, 3, 4, and more than 4 years' follow-up, estimated using the numbers of individuals at CHR-P transitioning to psychosis at each time point. These analyses were complemented by meta-analytical Kaplan-Meier curves and speed of transition to psychosis (hazard rate). Random-effects meta-analysis, between-study heterogeneity analysis, study quality assessment, and meta-regressions were conducted. A total of 130 studies and 9222 individuals at CHR-P were included. The mean (SD) age was 20.3 (4.4) years, and 5100 individuals (55.3%) were male. The cumulative transition risk was 0.09 (95% CI, 0.07-0.10; k = 37; n = 6485) at 0.5 years, 0.15 (95% CI, 0.13-0.16; k = 53; n = 7907) at 1 year, 0.20 (95% CI, 0.17-0.22; k = 30; n = 5488) at 1.5 years, 0.19 (95% CI, 0.17-0.22; k = 44; n = 7351) at 2 years, 0.25 (95% CI, 0.21-0.29; k = 19; n = 3114) at 2.5 years, 0.25 (95% CI, 0.22-0.29; k = 29; n = 4029) at 3 years, 0.27 (95% CI, 0.23-0.30; k = 16; n = 2926) at 4 years, and 0.28 (95% CI, 0.20-0.37; k = 14; n = 2301) at more than 4 years. The cumulative Kaplan-Meier transition risk was 0.08 (95% CI, 0.08-0.09; n = 4860) at 0.5 years, 0.14 (95% CI, 0.13-0.15; n = 3408) at 1 year, 0.17 (95% CI, 0.16-0.19; n = 2892) at 1.5 years, 0.20 (95% CI, 0.19-0.21; n = 2357) at 2 years, 0.25 (95% CI, 0.23-0.26; n = 1444) at 2.5 years, 0.27 (95% CI, 0.25-0.28; n = 1029) at 3 years, 0.28 (95% CI, 0.26-0.29; n = 808) at 3.5 years, 0.29 (95% CI, 0.27-0.30; n = 737) at 4 years, and 0.35 (95% CI, 0.32-0.38; n = 114) at 10 years. The hazard rate only plateaued at 4 years' follow-up. Meta-regressions showed that a lower proportion of female individuals (β = -0.02; 95% CI, -0.04 to -0.01) and a higher proportion of brief limited intermittent psychotic symptoms (β = 0.02; 95% CI, 0.01-0.03) were associated with an increase in transition risk. Heterogeneity across the studies was high (I2 range, 77.91% to 95.73%). In this meta-analysis, 25% of individuals at CHR-P developed psychosis within 3 years. Transition risk continued increasing in the long term. Extended clinical monitoring and preventive care may be beneficial in this patient population.

Clinical Features of Youth Depression with Attenuated Symptoms of the Schizophrenic Spectrum

Objective: establishment of clinical and psychometric features of youth depression with attenuated symptoms of the schizophrenic spectrum (ASSS) for early differential diagnosis and nosological assessment.Patients and methods: clinical and psychometric examination of young 219 inpatients (average age 19.6 ± 2.4 years), first admitted to the clinic “Mental Health Research Centre” from 2011 to 2020 with the first depressive episode with ASSS. Control group of inpatients (52 patients) with “classical” youth depressions without ASSS (average age 19.6 ± 2.4 years). Diagnosis according ICD-10: F32.1, F32.2, F32.28, F32.8.Results: the psychopathological structure of youth depression with ASSS is characterized by the following types: (1) depression with attenuated psychotic symptoms (APS), which were divided into the subtype (1a) depression with APS and (1b) depression with brief limited intermittent psychotic symptoms (BLIPS); (2) depression with attenuated negative symptoms (ANS), comprising two subtypes (2a) with most emotional damage and (2b) with volitional impairment, and type (3) with attenuated symptoms of disorganization (ASD) in the structure of depressive episode. Clinical and reliable psychometric differences have been established between depressions with ASSS and «classical» youth depressions without ASSS. Conclusions: youth depression with ASSS is definitely different from “classical” youth depression without ASSS. Differences have been found in the psychopathological structure of youth depression with ASSS, resulting in a typological differentiation.

Clinical outcomes in brief psychotic episodes: a systematic review and meta-analysis.

Patients with brief psychotic episodes (BPE) have variable and fluctuating clinical outcomes which challenge psychiatric care. Our meta-analysis aims at providing a comprehensive summary of several clinical outcomes in this patient group. A multistep systematic PRISMA/MOOSE-compliant literature search was performed for articles published from inception until 1st March 2021. Web of Science database was searched, complemented by manual search of original articles reporting relevant outcomes (psychotic recurrence, prospective diagnostic change or stability, remission, quality of life, functional status, mortality and their predictors) for patients diagnosed with acute and transient psychotic disorders (ATPD), brief psychotic disorders (BPD), brief intermittent psychotic symptoms (BIPS) and brief limited intermittent psychotic symptoms (BLIPS). Random-effects methods and Q-statistics were employed, quality assessment with Newcastle-Ottawa Scale, assessment of heterogeneity with I2 index, sensitivity analyses (acute polymorphic psychotic disorders, APPD) and multiple meta-regressions, assessment of publication bias with funnel plot, Egger's test and meta-regression (psychotic recurrence and sample size). A total of 91 independent articles (n = 94 samples) encompassed 37 ATPD, 24 BPD, 19 BLIPS and 14 BIPS samples, totalling 15 729 individuals (mean age: 30.89 ± 7.33 years, mean female ratio: 60%, 59% conducted in Europe). Meta-analytical risk of psychotic recurrence for all BPE increased from 15% (95% confidence interval (CI) 12-18) at 6 months, 25% (95% CI 22-30) at 12 months, 30% (95% CI 27-33) at 24 months and 33% (95% CI 30-37) at ⩾36 months follow-up, with no differences between ATPD, BPD, BLIPS and BIPS after 2 years of follow-up. Across all BPE, meta-analytical proportion of prospective diagnostic stability (average follow-up 47 months) was 49% (95% CI 42-56); meta-analytical proportion of diagnostic change (average follow-up 47 months) to schizophrenia spectrum psychoses was 19% (95% CI 16-23), affective spectrum psychoses 5% (95% CI 3-7), other psychotic disorders 7% (95% CI 5-9) and other (non-psychotic) mental disorders 14% (95% CI 11-17). Prospective diagnostic change within APPD without symptoms of schizophrenia was 34% (95% CI 24-46) at a mean follow-up of 51 months: 18% (95% CI 11-30) for schizophrenia spectrum psychoses and 17% (95% CI 10-26) for other (non-psychotic) mental disorders. Meta-analytical proportion of baseline employment was 48% (95% CI 38-58), whereas there were not enough data to explore the other outcomes. Heterogeneity was high; female ratio and study quality were negatively and positively associated with risk of psychotic recurrence, respectively. There were no consistent factor predicting clinical outcomes. Short-lived psychotic episodes are associated with a high risk of psychotic recurrences, in particular schizophrenia spectrum disorders. Other clinical outcomes remain relatively underinvestigated. There are no consistent prognostic/predictive factors.

Outreach and support in South-London (OASIS) 2001—2020: Twenty years of early detection, prognosis and preventive care for young people at risk of psychosis

This study aims to describe twenty years of early detection, prognosis and preventive care in the Outreach and Support In South-London (OASIS) mental health service for individuals at Clinical High risk of psychosis (CHR-P). The study presents a comprehensive analysis of the 2001– 2020 activity of the OASIS team encompassing core domains: (i) service characteristics, (ii) detection, (iii) prognosis, (iv) treatment and (v) clinical research. The analyses employed descriptive statistics, population-level data, the epidemiological incidence of psychosis, Kaplan Meier failure functions and Greenwood 95% CIs and Electronic Health Records. OASIS is part of the South London and Maudsley (SLaM) NHS trust, the largest European mental health provider, serving a total urban population of 1,358,646 individuals (population aged 16-35: 454,525). Incidence of psychosis in OASIS's catchment area ranges from 58.3 to 71.9 cases per 100,000 person-years, and it is higher than the national average of 41.5 cases per 100,000 person-year. OASIS is a standalone, NHS-funded, multidisciplinary (team leader, consultant and junior psychiatrists, clinical psychologists, mental health professionals), transitional (for those aged 14-35 years) community mental health service with a yearly caseload of 140 CHR-P individuals. OASIS regularly delivers a comprehensive service promotion outreach to several local community organisations. Referrals to OASIS (2366) are made by numerous agencies; about one-third of the referrals eventually met CHR-P criteria. Overall, 600 CHR-P individuals (55.33% males, mean age 22.63 years, white ethnicity 46.44%) have been under the care of the OASIS service: 80.43% met attenuated psychotic symptoms, 18.06% brief and limited intermittent psychotic symptoms and 1.51% genetic risk and deterioration CHR-P criteria. All CHR-P individuals were offered cognitive behavioural therapy and psychosocial support; medications were used depending on individual needs. The cumulative risk of psychosis at ten years was 0.365 (95%CI 0.302-0.437). At six years follow-up, across two-third of individuals non-transitioning to psychosis, 79.24% still displayed some mental health problem, and only 20.75% achieved a complete clinical remission. Research conducted at OASIS encompassed clinical, prognostic, neurobiological and interventional studies and leveraged local, national and international infrastructures; over the past ten years, OASIS-related research attracted about £ 50 million of grant income, with 5,922 citations in the international databases. Future developments may include broadening OASIS to prevent other serious mental disorders beyond psychosis and fostering translational risk prediction and interventional research. With a twenty-years activity, OASIS’ cutting-edge quality of preventive care, combined with translational research innovations, consolidated the service as a leading reference model for evidence-based prevention of psychosis worldwide.

Clinical High Risk Psychosis: Issues of Diagnostics and Therapy

The aim of the review: the analysis of modern Russian and foreign literature dedicated to the problem of determining diagnostic criteria for clinical high risk of psychosis (CHR-P) and outlining the therapeutic approaches based on the pathogenic mechanisms of their development. Material and method: the publications found by searching queries for keywords in Russian and English in the MEDLINE/PubMed and eLIBRARY databases for the time period from 2010 to 2020 were then analyzed. Conclusion: the review presents a modern definition of the CHR-P group, along with a clarification of individual diagnostic criteria, which include attenuated psychotic symptoms (APS), brief limited intermittent psychotic symptoms (BLIPS), genetic risk with deterioration of premorbid functioning, as well as basic symptoms (BS). We found heterogeneity of the CHR-P group with different levels of manifestation and outcomes and indicated the involvement of different pathogenic mechanisms in their formation. These findings determine the development of various approaches to treatment, which involve the assessment of the ratio of potential benefits and the risks of side effects. The obtained data, on the one hand, attest to the prospective viability of the therapeutic approach to the patients with CHR-P with the possibility of influencing the course of the disease, delaying its manifestation and improving long-term outcomes, and, on the other hand, the lack of universal standards of therapy at present. Tactics of treatment are determined basing on an individual approach to the patient with a comprehensive psychopathological assessment of complaints, clinical state and its dynamics.

Unmet needs for treatment in 102 individuals with brief and limited intermittent psychotic symptoms (BLIPS): implications for current clinical recommendations.

To investigate clinical outcomes and unmet needs in individuals at Clinical High Risk for Psychosis presenting with Brief and Limited Intermittent Psychotic Symptoms (BLIPS). Prospective naturalistic long-term (up to 9 years) cohort study in individuals meeting BLIPS criteria at the Outreach And Support In South-London (OASIS) up to April 2016. Baseline sociodemographic and clinical characteristics, specific BLIPS features, preventive treatments received and clinical outcomes (psychotic and non-psychotic) were measured. Analyses included Kaplan Meier survival estimates and Cox regression methods. One hundred and two BLIPS individuals were followed up to 9 years. Across BLIPS cases, 35% had an abrupt onset; 32% were associated with acute stress, 45% with lifetime trauma and 20% with concurrent illicit substance use. The vast majority (80%) of BLIPS individuals, despite being systematically offered cognitive behavioural therapy for psychosis, did not fully engage with it and did not receive the minimum effective dose. Only 3% of BLIPS individuals received the appropriate dose of cognitive behavioural therapy. At 4-year follow-up, 52% of the BLIPS individuals developed a psychotic disorder, 34% were admitted to hospital and 16% received a compulsory admission. At 3-year follow-up, 52% of them received an antipsychotic treatment; at 4-year follow-up, 26% of them received an antidepressant treatment. The presence of seriously disorganising and dangerous features was a strong poor prognostic factor. BLIPS individuals display severe clinical outcomes beyond their very high risk of developing psychosis and show poor compliance with preventive cognitive behavioural therapy. BLIPS individuals have severe needs for treatment that are not met by current preventive strategies.

Distinguishing prodromal stage of bipolar disorder and early onset schizophrenia spectrum disorders during adolescence

Prodromal symptoms of bipolar disorder (BD) and early onset schizophrenia spectrum disorder (EOSSD) overlap. To date, there has been no study directly comparing the prodromal stage of both disorders. Thus, the current study is aimed at determining which prodromal symptom clusters differentiate BD and EOSSD. One hundred twenty one adolescents (33 BD-1, 30 EOSSD, 58 healthy controls) were evaluated for the presence of 79 prodromal symptoms, divided into 7 prodromal symptom clusters. Great than 2 subsyndromal manic symptoms and ADHD comorbidity were significantly more specific for BD than schizophrenia; brief limited intermittent psychotic symptoms (BLIPS) were more likely to be part of EOSSD. In contrast, attenuated psychotic symptoms, and negative symptoms were not specifically related to the diagnosis of EOSSD. In conclusion, subsyndromal manic symptoms, BLIPS, and ADHD might be useful for predicting the trajectory of an emerging affective disorder versus schizophrenia and thus valuable for early detection, and intervention strategies.

Two-Year Clinical and Functional Outcomes of an Asian Cohort at Ultra-High Risk of Psychosis.

Background: To determine the 2-year clinical and functional outcomes of an Asian cohort at ultra-high risk (UHR) of psychosis.Method: This was a longitudinal study with a follow-up period of 2 years on 255 help-seeking adolescents and young adults at UHR of psychosis managed by a multi-disciplinary mental health team in Singapore. Clients received case management, psychosocial, and pharmacological treatment as appropriate. Data comprising symptom and functional outcomes were collected over the observation period by trained clinicians and psychiatrists.Results: The 2-year psychosis transition rate was 16.9%, with a median time to transition of 168 days. After 2 years, 14.5% of the subjects had persistent at-risk symptoms while 7.5% developed other non-psychotic psychiatric disorders. 38.4% of the cohort had recovered and was discharged from mental health services. The entire cohort's functioning improved as reflected by an increase in the score of the Social and Occupational Functioning Assessment Scale during the follow-up period. Predictors to psychosis transition included low education level, baseline unemployment, a history of violence, and brief limited intermittent psychotic symptoms, while male gender predicted the persistence of UHR state, or the development of non-psychotic disorders.Conclusion: Use of the current UHR criteria allows us to identify individuals who are at imminent risk of developing not just psychosis, but also those who may develop other mental health disorders. Future research should include identifying the needs of those who do not transition to psychosis, while continuing to refine on ways to improve the UHR prediction algorithm for psychosis.

Characterization of children and adolescents with psychosis risk syndrome: The Children and Adolescents Psychosis Risk Syndrome (CAPRIS) study.

Despite the interest in psychosis risk syndrome (PRS) in children and adolescents, information on the syndrome in this population is scarce. Prospective naturalistic multi-site study in which 10- to 17-year-old help-seeking subjects who met PRS criteria (positive or negative attenuated symptoms; brief limited intermittent psychotic symptoms; genetic risk or schizotypal personality disorder plus impairment in functioning) were included, along with 45 age and sex-matched healthy controls (HC). All subjects were clinically and functionally assessed. Ninety-one PRS subjects (PRSS) with a mean age of 15.5 ± 1.4 met inclusion criteria (IC). Compared with HC, PRSS presented worse global and academic functioning in the previous year, had experienced more psychiatric and psychological problems, and presented gestational ages outside the normal range. More than 80% of PRSS met ≥2 IC, with 65.9% having one Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Text Revision diagnosis, and 61.7% of those having ≥2 diagnoses. Some 49.5% of PRSS had a first- or second-degree family history (FH) of psychosis. Patients with first- and second-degree FH do not differ in their clinical expression. Children and adolescents with PRS are a patient group with a pattern of neurodevelopmental impairment and clinical complexity similar to patients with schizophrenia spectrum disorders, highlighting the importance of assessing these variables in child and adolescent samples. PRSS with first- and second-degree relatives with FH do not present differences in their clinical presentation, suggesting that including these two groups of patients in the genetic risk criteria would enrich knowledge of these criteria.

Federated multi-site longitudinal study of at-risk mental state for psychosis in Japan

There has been recent accumulation of evidence and clinical guidance regarding the at-risk mental state (ARMS) for psychosis. However, most studies have been observational cohort and intervention studies of Western populations. To assess the validity of the ARMS concept and the transition rate to psychosis in a non-Western nation, we retrospectively combined and analyzed clinical data of individuals diagnosed with ARMS who were prospectively followed-up at three specialized clinical services for ARMS in Japan. In total, we included 309 individuals with ARMS, of whom 43 developed overt psychosis. We estimated cumulative transition rates to psychosis with the Kaplan-Meier method, obtaining rates of 12% at 12, 16% at 24, 19% at 36, and 20% at 48 months. Only two individuals reported past cannabis use. Despite several differences among the three sites, transition rates did not differ among them. Furthermore, the transition rate of children aged between 14 and 17 years did not differ from that of individuals aged 18 years or older. Regression analysis revealed that meeting the brief limited intermittent psychotic symptoms (BLIPS) criterion was associated with an increased risk of transition to psychosis, whereas genetic risk factors were not. Although antipsychotic prescription was relatively frequent in this cohort, there was no evidence supporting frequent use of antipsychotics for this population. In conclusion, our findings support the assertion that the current concept of ARMS is applicable in Japan. Development of local clinical guidelines and training for clinicians is necessary to disseminate this concept to more clinical settings.

Exploring the predictive power of the unspecific risk category of the Basel Screening Instrument for Psychosis.

Ultrahigh risk (UHR) criteria, consisting of brief limited intermittent psychotic symptoms (BLIPS), attenuated psychotic symptoms (APS) and genetic risk and deterioration (GRD) syndrome are the most widely used criteria for assessing the clinical high-risk state for psychosis (CHR-P). The Basel Screening Instrument for Psychosis (BSIP) includes a further risk category, the unspecific risk category (URC). However, little is known about the predictive power of this risk category compared to other risk categories. Two hundred CHR-P patients were detected as part of the Früherkennung von Psychosen (FePsy) study using the BSIP. Transition to psychosis was assessed in regular intervals for up to 7 years. Patients meeting only the URC criterion (n = 40) had a significantly lower risk of transition to psychosis than the UHR group (including BLIPS, APS and GRD) (HR 0.19 [0.05; 0.80] (P = 0.024). Furthermore, the URC only risk group had a lower transition risk than the APS without BLIPS group (P = 0.015) and a trendwise lower risk than the BLIPS group (P = 0.066). However, despite the lower transition risk in the URC only group, there were still two patients (5%) in this group with a later transition to psychosis. The URC includes patients who have a lower risk of transition than those included by the UHR categories and thereby increases the sensitivity of the BSIP. This offers the possibility of a stratified intervention, with these subjects receiving low intensity follow-up and treatment.

Ultra-high risk psychosis. A case report

IntroductionThere is much debate on whether patients who are at high risk of developing a psychotic disorder in the near future (such as patients suffering of attenuated psychotic symptoms, brief limited intermittent psychotic symptoms or personality trait vulnerability) should be treated with antipsychotic drugs to prevent possible psychotic breaks from happening.AimTo review articles from the existing medical literature about treatment of patients in ultra-high risk of developing psychosis.MethodsWe describe the case of a 19-year-old male who was hospitalized after a suicide attempt in April 2015. He had been diagnosed of different psychiatric disorders such as mixed anxiety-depressive disorder, adjustment disorder and probable borderline personality disorder. During his stay at the hospital, we observed that he had schizoid personality traits. In the initial anamnesis, he denied ever having psychotic symptoms, but a few days later he admitted that the previous year he suffered throw a period of brief self-limiting psychotic symptoms.ResultsProphylactic treatment was started with oral aripiprazole 15 mg/day, which was well tolerated by the patient. He has been free of psychotic symptoms for the last 17 months (from April 2015 to September 2016). No relevant side effects were detected.ConclusionsOral aripiprazole 15 mg/day can be a good therapeutic option in patients at ultra-high risk of developing a psychotic episode.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Long-term rates of remission and late psychotic transition of individuals at risk for psychosis

IntroductionIn the growing research field of early psychosis detection in patients with an at risk mental state (ARMS), most studies focus on the transition to frank psychosis. However, the majority of ARMS patients do not go on to develop frank psychosis and reported transition rates are declining. Little is known about the long-term outcome of these non-transitioned patients (ARMS-NT).ObjectivesTo investigate in preliminary analyses the long-term outcome of ARMS-NT patients with respect to persistence of ARMS signs and symptoms and the rates of late psychotic transition.MethodsThe ongoing study “FePsy-BHS-NT” follows up ARMS-NT without transition during at least the first two years for up to 15 years after their initial assessment. ARMS status is ascertained with the Basel Screening Instrument for Psychosis (BSIP). ARMS remission is defined as the absence of attenuated psychotic symptoms or brief limited intermittent psychotic symptoms for at least 12 consecutive months.ResultsIn this preliminary sample of 51 ARMS-NT, the majority of patients (70.6%) have remitted from their at risk mental state, 13.7% remain at risk and 15.7% have made a late psychotic transition during the course of long-term follow up (median = 5.75, range 4–11 years after initial assessment).ConclusionsThe considerable rates of ARMS persistence and late psychotic transition indicate that longer follow-up durations than commonly recommended should be contemplated in ARMS patients. Potential predictors of favorable long-term clinical outcome, as well as psychosocial, neurocognitive and other outcomes of ARMS-NT patients will be further evaluated in the present study.Disclosure of interestThe authors have not supplied their declaration of competing interest.

15. Neuronal Autoantibodies and Blood-Brain Barrier Disruption in Subjects at Ultra-High Risk for Psychosis

Abstract Background: Neuronal surface autoantibodies (NSAbs) have been identified in patients with psychotic disorders, with meta-analytical evidence indicating a higher prevalence in first-episode psychosis (FEP), probably dependent on the assay used. The causal significance of these NSAbs is unclear, with a suggestion that that blood–brain barrier disruption (BBBD) may be an important additional factor. We aimed to establish whether, prior to illness onset, NSAbs and BBBD are present in subjects at ultra-high risk (UHR) for psychosis. Methods: Sera from 260 UHR subjects in the EUGEI study and 110 healthy controls were tested with a fixed cell-based assay (CBA) using HEK293 cells that had been transfected to express one of 30+ NSAbs; IgG, IgA and IgM binding was assessed using indirect immunofluorescence. Levels of S100B, a putative marker of BBBD, were assessed using a chemoluminescence assay in this cohort and an FEP cohort (n = 226). Results: NSAbs were present in 8.8% of UHR subjects and 7.3% HCs (ns) with NMDAR the most frequent antigen. Serostatus did not predict transition to psychosis, and 2 of 3 seropositive patients who transitioned to psychosis had antibodies of diverse Ig isotype. Patients with brief limited intermittent psychotic symptoms (BLIPS) were twice as likely to be seropositive at baseline compared to patients who transitioned to psychosis. Interestingly, subjects who were positive on fixed CBA for any NSAb or for only NMDAR antibodies showed trends towards higher negative syndrome scores across multiple scales. These subjects had impaired verbal memory scores as measured by the Rey auditory verbal learning test (RAVLT) (P = .0019), a finding that mirrors patients with NMDAR encephalitis and may be reflective of hippocampal dysfunction.Samples were also tested for NMDAR IgG antibodies using a live CBA; this detected a higher prevalence of NMDAR IgG antibodies in the total cohort than did fixed CBA (19 subjects (5.1%) vs 2 (0.5%); P = .0025).Mean S100B levels were higher in FEP subjects than in UHR subjects (P < .001) and controls (P < .0001). UHR subjects with high S100B levels surprisingly showed lower total psychopathology scores (BPRS; P = .032), less negative symptoms (SANS; P = .039), and disability (GAF; P = .009), whereas in FEP S100B levels were associated with worse positive psychotic symptoms. Conclusion: A minority of subjects at risk of psychosis have NSAbs detectable in serum: These individuals may have worse negative symptoms and demonstrate impaired neurocognition. Further work is required to clarify the immunological and neuroanatomical substrates of these changes. BBBD may be progressive with the development of psychosis. The paradoxical finding of improved symptoms and function in subjects with evidence of greater BBBD differentiates UHR subjects from later stage psychosis and represents an exciting avenue for further investigation.This work was supported by a grant from The Wellcome Trust.

Clinical Practice Guidelines for Management of Schizophrenia.

Clinical Practice Guidelines for Management of Schizophrenia.

Long-term validity of the At Risk Mental State (ARMS) for predicting psychotic and non-psychotic mental disorders

BackgroundThe long-term clinical validity of the At Risk Mental State (ARMS) for the prediction of non-psychotic mental disorders is unknown. MethodsClinical register-based cohort study including all non-psychotic individuals assessed by the Outreach And Support in South London (OASIS) service (2002–2015). The primary outcome was risk of developing any mental disorder (psychotic or non-psychotic). Analyses included Cox proportional hazard models, Kaplan–Meier survival/failure function and C statistics. ResultsA total of 710 subjects were included. A total of 411 subjects were at risk (ARMS+) and 299 not at risk (ARMS−). Relative to ARMS−, the ARMS+ was associated with an increased risk (HR=4.825) of developing psychotic disorders, and a reduced risk (HR=0.545) of developing non-psychotic disorders (mainly personality disorders). At 6-year, the ARMS designation retained high sensitivity (0.873) but only modest specificity (0.456) for the prediction of psychosis onset (AUC 0.68). The brief and limited intermittent psychotic symptoms (BLIPS) subgroup had a higher risk of developing psychosis, and a lower risk of developing non-psychotic disorders as compared to the attenuated psychotic symptoms (APS) subgroup (P<0.001). ConclusionsIn the long-term, the ARMS specifically predicts the onset of psychotic disorders, with modest accuracy, but not of non-psychotic disorders. Individuals meeting BLIPS criteria have distinct clinical outcomes. Significant outcomesIn the long-term, the ARMS designation is still significantly associated with an increased risk of developing psychotic disorders but its prognostic accuracy is only modest. There is no evidence that the ARMS is associated with an increased risk of developing non-psychotic mental disorders. The BLIPS subgroup at lower risk of developing non-psychotic disorders compared to the APS subgroup. LimitationsWhile incident diagnoses employed in this study are high in ecological validity they have not been subjected to formal validation with research-based criteria.