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.

Study protocol: Epigenetic variations associated to the conversion of schizophrenia in ultra-high risk adolescents, a 4-year follow-up study

IntroductionSchizophrenia is a severe mental disorder characterized by negative (e.g., social withdrawal, apathy, anhedonia) and positive (e.g., hallucinations, delusions, disorganized behaviour) symptoms. Schizophrenia prodromal symptoms typically emerge during the adolescence. These symptoms consist of attenuated and/or intermittent psychotic symptoms and define the ultra-high risk (UHR) states of schizophrenia. Approximately, 30% of UHR individuals develop schizophrenia. It is important to find biomarkers associated with the conversion of schizophrenia in UHR individuals in order to develop preventive and therapeutic strategies, as well as to gain knowledge in the ethiopathology of the disorder. In this regard, epigenetic variations have been identified as potential biomarkers associated with the conversion to schizophrenia, but the lack of research prevent to draw final conclusions.ObjectivesThe objective of this communication is to report the study protocol of the research project named “Epigenetic variations associated with the conversion of schizophrenia in ultra-high risk adolescents”. Its aim is to analyze the epigenetic marks that predict the development of schizophrenia in UHR youths.MethodsA 4-year observational follow-up study will be conducted, assessing three groups of adolescents who have sought clinical hep: 1) UHR group composed of individuals who have developed schizophrenia at the end of the follow-up; 2) UHR group composed of individuals who did not develop schizophrenia at the end of the follow-up; 3) a group composed of non-UHR individuals. Epigenetic marks will be analyzed in the peripheral blood of all the participants each 6 months. Clinical (i.e., positive and negative symptoms, depressive symptoms, anxiety symptoms, global functioning, traumatic events, alcohol and other toxics consumption) and sociodemographic data (i.e., age, sex, migration status, ethnicity, socio-cultural status, academic achievements) will be also assessed through standardized questionnaires.ResultsWe hypothesize that specific epigenetic marks will predict the conversion of schizophrenia in the UHR group. Moreover, interactions between epigenetic variations and sociodemographic data will differentiate the three groups after the follow-up.ConclusionsThe findings of this project will help to develop preventive and therapeutic strategies, as well as to gain knowledge in the etiopathological pathways of schizophrenia.Disclosure of InterestNone Declared

The 'Parma At-Risk mental states' (PARMS) program: General description and process analysis after 5 years of clinical activity.

From January 2016, the Parma Department of Mental Health developed a specialized care protocol - the 'Parma At-Risk Mental States' (PARMS) program - as a diffused service for early intervention in individuals at Clinical High Risk for Psychosis (CHR-P). The aims of this investigation were (1) to describe the PARMS structural organization and (2) to examine specific process indicators during the first 5 years of its clinical activity. All participants were adolescent and young adult help-seekers (aged 12-25 years) at CHR-P in accordance with well-defined psychometric criteria. At entry, 52 subjects were provided with a dedicated protocol of care and only 14 dropped out during the first year of treatment. The Duration of Untreated Illness (DUI) overall decreased over time. Most of CHR-P participants suffered from 'Attenuated Psychotic Symptoms' and 'Brief, Limited, Intermittent Psychotic Symptoms' in the same percentage (48.1% [n= 25]). The most common DSM-IV-TR diagnosis was schizotypal personality disorder, followed by borderline personality disorder and brief psychotic disorder. A specialized, evidence-based care protocol for CHR-P individuals within Italian adult and child/adolescent psychiatric services is feasible, also in adolescents, who have a high risk of falling through the child/adult service gap.

The heterogeneity of attenuated and brief limited psychotic symptoms: association of contents with age, sex, country, religion, comorbidities, and functioning.

The Attenuated Psychosis Symptoms (APS) syndrome mostly represents the ultra-high-risk state of psychosis but, as does the Brief Intermittent Psychotic Symptoms (BIPS) syndrome, shows a large variance in conversion rates. This may be due to the heterogeneity of APS/BIPS that may be related to the effects of culture, sex, age, and other psychiatric morbidities. Thus, we investigated the different thematic contents of APS and their association with sex, age, country, religion, comorbidity, and functioning to gain a better understanding of the psychosis-risk syndrome. A sample of 232 clinical high-risk subjects according to the ultra-high risk and basic symptom criteria was recruited as part of a European study conducted in Germany, Italy, Switzerland, and Finland. Case vignettes, originally used for supervision of inclusion criteria, were investigated for APS/BIPS contents, which were compared for sex, age, country, religion, functioning, and comorbidities using chi-squared tests and regression analyses. We extracted 109 different contents, mainly of APS (96.8%): 63 delusional, 29 hallucinatory, and 17 speech-disorganized contents. Only 20 contents (18.3%) were present in at least 5% of the sample, with paranoid and referential ideas being the most frequent. Thirty-one (28.5%) contents, in particular, bizarre ideas and perceptual abnormalities, demonstrated an association with age, country, comorbidity, or functioning, with regression models of country and obsessive-compulsive disorders explaining most of the variance: 55.8 and 38.3%, respectively. Contents did not differ between religious groups. Psychosis-risk patients report a wide range of different contents of APS/BIPS, underlining the psychopathological heterogeneity of this group but also revealing a potential core set of contents. Compared to earlier reports on North-American samples, our maximum prevalence rates of contents were considerably lower; this likely being related to a stricter rating of APS/BIPS and cultural influences, in particular, higher schizotypy reported in North-America. The various associations of some APS/BIPS contents with country, age, comorbidities, and functioning might moderate their clinical severity and, consequently, the related risk for psychosis and/or persistent functional disability.

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.

Clinical outcomes in individuals at clinical high risk of psychosis who do not transition to psychosis: a meta-analysis.

The clinical outcomes of individuals at clinical high risk of psychosis (CHR-P) who do not transition to psychosis are heterogeneous and inconsistently reported. We aimed to comprehensively evaluate longitudinally a wide range of outcomes in CHR-P individuals not developing psychosis. "Preferred Reporting Items for Systematic reviews and Meta-Analyses" and "Meta-analysis Of Observational Studies in Epidemiology"-compliant meta-analysis (PROSPERO: CRD42021229212) searching original CHR-P longitudinal studies in PubMed and Web of Science databases up to 01/11/2021. As primary analysis, we evaluated the following outcomes within CHR-P non-transitioning individuals: (a) change in the severity of attenuated psychotic symptoms (Hedge's g); (b) change in the severity of negative psychotic symptoms (Hedge's g); (c) change in the severity of depressive symptoms (Hedge's g); (d) change in the level of functioning (Hedge's g); (e) frequency of remission (at follow-up). As a secondary analysis, we compared these outcomes in those CHR-P individuals who did not transition vs. those who did transition to psychosis at follow-up. We conducted random-effects model meta-analyses, sensitivity analyses, heterogeneity analyses, meta-regressions and publication bias assessment. The risk of bias was assessed using a modified version of the Newcastle-Ottawa Scale (NOS). Twenty-eight studies were included (2756 CHR-P individuals, mean age = 20.4, 45.5% females). The mean duration of follow-up of the included studies was of 30.7 months. Primary analysis: attenuated psychotic symptoms [Hedges' g = 1.410, 95% confidence interval (CI) 1.002-1.818]; negative psychotic symptoms (Hedges' g = 0.683, 95% CI 0.371-0.995); depressive symptoms (Hedges' g = 0.844, 95% CI 0.371-1.317); and functioning (Hedges' g = 0.776, 95% CI 0.463-1.089) improved in CHR-P non-transitioning individuals; 48.7% remitted at follow-up (95% CI 39.3-58.2%). Secondary analysis: attenuated psychotic symptoms (Hedges' g = 0.706, 95% CI 0.091-1.322) and functioning (Hedges' g = 0.623, 95% CI 0.375-0.871) improved in CHR-P individuals not-transitioning compared to those transitioning to psychosis, but there were no differences in negative or depressive symptoms or frequency of remission (p > 0.05). Older age was associated with higher improvements of attenuated psychotic symptoms (β = 0.225, p = 0.012); publication years were associated with a higher improvement of functioning (β = -0.124, p = 0.0026); a lower proportion of Brief Limited Intermittent Psychotic Symptoms was associated with higher frequencies of remission (β = -0.054, p = 0.0085). There was no metaregression impact for study continent, the psychometric instrument used, the quality of the study or proportion of females. The NOS scores were 4.4 ± 0.9, ranging from 3 to 6, revealing the moderate quality of the included studies. Clinical outcomes improve in CHR-P individuals not transitioning to psychosis but only less than half remit over time. Sustained clinical attention should be provided in the longer term to monitor these outcomes.

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.

Neural Correlates of Mentalizing in Individuals With Clinical High Risk for Schizophrenia: ALE Meta-Analysis.

Psychotic disorder refers to a spectrum of disorders that have multiple etiologies, due to the complex interaction of biological and genetic vulnerability with familial and cultural factors. A clinical high risk (CHR) for schizophrenia is defined as the presence of brief, attenuated, or intermittent psychotic symptoms in non-schizophrenic individuals. The transition to schizophrenia appears significantly more frequent in this at-risk population than in the general population. Moreover, the ability to attribute mental states to others, known as mentalizing or theory of mind, and its neural correlates found in individuals with CHR are similar to those described in patients with schizophrenia. We have therefore explored neurofunctional correlates of mentalizing in individuals with CHR vs. healthy controls, in order to identify the differences in brain activation. A neural coordinate-based activation likelihood estimation meta-analysis of existing neuroimaging data revealed that three regions displayed decreased activation in individuals with CHR, compared with healthy controls: the right temporoparietal junction, the right middle temporal gyrus, and the left precuneus. These results, combined with those in the literature, further support the hypothesis that abnormal activation of posterior brain regions involved in mentalizing correlates with psychotic symptoms in help-seeking individuals.

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.

Real-world long-term outcomes in individuals at clinical risk for psychosis: The case for extending duration of care.

BackgroundMost services for individuals at Clinical High Risk for Psychosis (CHR-P) provide short-term clinical care. This study determines the real-world and long-term clinical outcomes beyond transition to psychosis in a large cohort of CHR-P individuals.MethodRetrospective RECORD-compliant real-world Electronic Health Records (EHR) cohort study in secondary mental health care (the South London and the Maudsley -SLaM- NHS Foundation Trust). All CHR-P patients accessing the CHR-P service at SLaM in the period 2001–2018 were included. Main outcomes were long-term cumulative risk of first: (i) developing an ICD-10 psychotic disorder (primary outcome), receiving a treatment with (iia) antipsychotic medication, (iib) benzodiazepines, (iic) other psychotropic medications, (iid) psychotherapy, receiving an (iiia) informal or (iiib) compulsory admission into a mental health hospital, and the time to these events; (iiic) number of days spent in hospital and (iv) cumulative risk of death for any reason and age/gender Standardised Mortality Ratio (SMR). Data were extracted from the EHR and analysed with Kaplan Meier failure functions, Cox and zero-inflated negative binomial regressions.Findings600 CHR-P patients (80.43% Attenuated Psychotic Symptoms, APS; 18.06%, Brief and Limited Intermittent Psychotic Symptoms, BLIPS, 1.51% Genetic Risk and Deterioration Syndrome) were included (mean age 22.63 years, range 13–36; 55.33% males; 46.44% white, mean duration of untreated attenuated psychotic symptoms 676.32 days, 1105.40 SD). The cumulative risk to first psychosis was 0.365 (95%CI 0.302–0.437) at 11 years; first antipsychotic 0.777 (95%CI 0.702–0.844) at 9 years; first benzodiazepine 0.259 (95%CI 0.183–0.359) at 12 years; first other types of medications 0.630 (95%CI 0.538–0.772) at 9 years; first psychotherapy 0.814 (95%CI 0.764–0.859) at 9 years; first informal admission 0.378 (95%CI 0.249–0.546) at 12 years; first compulsory admission 0.251 (95%CI 0.175–0.352) at 12 years; those admitted spent on average 94.84 (SD=169.94) days in hospital; the cumulative risk of death for any reason was 0.036 (95%CI 0.012–0.103) at 9 years, with an SMR of 3.9 (95%CI 1.20–6.6). Compared to APS, BLIPS had a higher risk of developing psychosis, being admitted compulsorily into hospital, receiving antipsychotics and benzodiazepines and lower probability of receiving psychotherapy. Other prognostic factors of long-term outcomes included age, symptoms severity, duration of untreated attenuated psychotic symptoms, ethnicity and employment status.InterpretationDuration of care provided by CHR-P services should be expanded to address long-term real-world outcomes.FundingThis study was supported by the King's College London Confidence in Concept award from the Medical Research Council (MRC) (MC_PC_16048) to PF-P. GSP is supported by the Alicia Koplowitz Foundation. HB is supported by a National Institute for Health Research Maudsley Biomedical Research Centre studentship.

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.

Effects of age and sex on clinical high-risk for psychosis in the community.

BACKGROUNDRecent reports of both heightened prevalence rates and limited clinical relevance of clinical high-risk (CHR) criteria and their relevant symptoms in children and adolescents indicate an important role of neurodevelopment in the early detection of psychoses. Furthermore, sex effects in CHR symptoms have been reported, though studies were inconclusive. As sex also impacts on neurodevelopment, we expected that sex might have an additional contribution to age in the prevalence and clinical relevance of CHR symptoms and criteria.AIMTo investigate age and sex effects on CHR criteria and symptoms and their association with psychosocial impairment and mental disorder.METHODSIn this cross-sectional cohort study, n = 2916 8- to 40-year-olds, randomly drawn from the population register of the Swiss canton Bern, were assessed in semi-structured interviews by phone or face-to-face for CHR symptoms and criteria using the Structured Interview for Psychosis-Risk Syndromes and the Schizophrenia Proneness Instrument in its child and youth, and adult version, respectively. Furthermore, social and occupational functioning and DSM-IV axis I disorders were assessed. Simple and interaction effects of age and sex on CHR symptoms and criteria, and interaction effects of age, sex, and CHR symptoms and criteria on presentation of functional impairment and of non-psychotic disorder were investigated using logistic regression analyses.RESULTSAltogether, 542 (18.6%) participants reported any CHR symptom; of these, 261 (9.0%) participants reported any one of the 11 criteria relevant cognitive and perceptual basic symptoms, and 381 (13.1%) any one of the five attenuated or transient psychotic symptoms (attenuated psychotic symptoms/brief intermittent psychotic symptoms). Fewer participants met any one of the CHR criteria (n = 82, 2.8%) or any one of the three recently recommended CHR criteria (n = 38, 1.3%). Both age and sex were significantly (P < 0.05) associated with CHR symptoms and criteria, mostly by younger age and female sex. Though slightly differing between symptom groups, age thresholds were detected around the turn from adolescence to adulthood; they were highest for cognitive basic symptoms and CHR criteria. With the exception of the infrequent speech disorganization attenuated psychotic symptom, the interaction of age with CHR symptoms and criteria predicted functional impairment; whereas, independent of each other, sex and CHR symptoms mostly predicted mental disorders.CONCLUSIONAge and sex differentially impact on CHR symptoms and criteria; these differences may support better understanding of causal pathways. Thus, future CHR studies should consider effects of sex and age.

S29. ONE-CARBON METABOLISM AND STRESS IN CHILDREN AND ADOLESCENTS WITH PSYCHOSIS RISK SYNDROME: PRELIMINARY DATA

BackgroundA dysregulation in one-carbon metabolism, involving folate, vitamin B12 and homocysteine (Hcys) could be implicated in the physiopathology of schizophrenia (for a review, Frankenburg, 2007). Higher Hcys levels have been associated with the disease compared to healthy controls in adults as well as in children and adolescents (Levere et al, 2014). Up to our knowledge, there are no studies in children and adolescents at risk for schizophrenia and other psychosis (Psychosis Risk Syndrome, PRS) testing the one-carbon metabolism parameters. Only a few groups have published results focused only in this population (for a review, Tor et al, 2018). This study aims to compare blood parameters associated with one-carbon metabolism, the clinical and demographic characteristics and stressful life events of a sample of children and adolescents with PRS and healthy controls (HC).MethodsA prospective longitudinal study in which help-seeking subjects who met PRS criteria were recruited from the Child and Adolescent Psychiatry and Psychology departments of Hospital Clinic and Hospital Sant Joan de Déu (Barcelona, Spain). Inclusion criteria were: 1) Attenuated positive or negative symptoms in the previous 12 months; 2) Brief intermittent psychotic symptoms; 3)First or second degree relative with schizophrenia or schizotypical disorder plus impairment of functioning; age:10–17 years. Exclusion criteria: IQ<70 and a diagnosis of neurodevelopmental disorder. At baseline, the Semistructured Interview for Prodromal Syndromes and Scale of Prodromal Symptoms (SIPS/SOPS) were administered, as well as a clinical scale battery including measures of stress such as the Stressful Live Events Scale. Blood analysis measuring vitamin B12, folic acid and homocysteine were done. Types of treatment, and dosages were also registered. A sample of age and gender matched HCs were also included. Exclusion criteria: 1st or 2nd degree familiar with a psychotic disorder; a diagnosis of neurodevelopmental disorder and IQ<70.The same assessment was performed in the HC sample.Results60 PRS subjects (14.9±1.8 years, range: 11–17 years; 74.1% females) and 40 HC (15.4±1.5 years, range: 11–17 years; 65% females) were included. In the PRS sample, 59.4% met criterion 1 for inclusion. 59.4% had familiar history of psychotic disorder. All the SOPS, GAF, LSP, Hamilton and Young scores were significantly higher in PRS than in HC. Number of stressful life events and their subjective affectation were also higher in PRS subjects than in HC (t=-4.939, p<<0.001; t=-5.380, p<0.001). There were no differences in Hcys and, folic acid levels between PRS subjects and HC. However, vitamin B12 levels were different between them, with lower levels in PRS vs HC (425.7±185.7 vs.526.4±159.1, t=2.755, p=0.007) without reaching deficit levels (<300 pg/mL). Higher Hcys levels was correlated with higher number of life events (R=0.245, p=0.037). Lower levels of vitamin B12 were correlated with higher number of stressful life events (R=-0.393, p=0.001) and higher subjective affectation (R=-0.381, p=0.001).DiscussionIn children and adolescents with PRS, lower vitamin B12 levels than HC have been found, which were associated with higher stressful life events and their subjective affectation. Vitamin B12 is key for brain development, and the possible dysregulation of one carbon metabolism and their association with stress in children and adolescents at risk for psychosis should be further explored as well as the diet of these subjects in a bigger sample to draw consistent conclusions.

Neuropsychological profile of children and adolescents with psychosis risk syndrome: the CAPRIS study.

Neuropsychological underperformance is well described in young adults at clinical high risk for psychosis, but the literature is scarce on the cognitive profile of at-risk children and adolescents. The aim of this study is to describe the neuropsychological profile of a child and adolescent sample of patients with psychosis risk syndrome (PRS) compared to healthy controls and to analyze associations between attenuated psychotic symptoms and cognitive impairment. Cross-sectional baseline data analysis from a longitudinal, naturalistic, case-control, two-site study is presented. Eighty-one help-seeking subjects with PRS and 39 healthy controls (HC) aged between 10 and 17years of age were recruited. PRS was defined by: positive or negative attenuated symptoms, Brief Limited Intermittent Psychotic Symptoms (BLIPS), genetic risk (first- or second-degree relative), or schizotypal personality disorder plus impairment in functioning. A neuropsychological battery was administered to assess general intelligence, verbal and visual memory, visuospatial abilities, speed processing, attention, and executive functions. The PRS group showed lower general neuropsychological performance scores at a multivariate level and lower scores than controls in general intelligence and executive functions. Lower scores on executive function and poorer attention were associated with high scores of positive attenuated psychotic symptoms. No association with attenuated negative symptoms was found. This study provides evidence of cognitive impairment in PRS children and adolescents and shows a relationship between greater cognitive impairment in executive functions and attention tasks and severe attenuated positive symptoms. However, longitudinal studies are needed to clarify the nature of cognitive impairment as a possible vulnerability marker.

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.