Aberrant brain dynamics in individuals with clinical high risk of psychosis.

Background: Resting-state network (RSN) functional connectivity analyses have profoundly influenced our understanding of the pathophysiology of psychoses and their clinical high risk (CHR) states. However, conventional RSN analyses address the static nature of large-scale brain networks. In contrast, novel methodological approaches aim to assess the momentum state and temporal dynamics of brain network interactions. Methods: Fifty CHR individuals and 33 healthy controls (HC) completed a resting-state functional MRI scan. We performed an Energy Landscape analysis, a data-driven method using the pairwise maximum entropy model, to describe large-scale brain network dynamics such as duration and frequency of, and transition between, different brain states. We compared those measures between CHR and HC, and examined the association between neuropsychological measures and neural dynamics in CHR. Results: Our main finding is a significantly increased duration, frequency, and higher transition rates to an infrequent brain state with coactivation of the salience, limbic, default mode and somatomotor RSNs in CHR as compared to HC. Transition of brain dynamics from this brain state was significantly correlated with processing speed in CHR. Conclusion: In CHR, temporal brain dynamics are attracted to an infrequent brain state, reflecting more frequent and longer occurrence of aberrant interactions of default mode, salience, and limbic networks. Concurrently, more frequent and longer occurrence of the brain state is associated with core cognitive dysfunctions, predictors of future onset of full-blown psychosis.

Normative Modeling of Brain Morphometry in Clinical High Risk for Psychosis.

Importance: The lack of robust neuroanatomical markers of psychosis risk has been traditionally attributed to heterogeneity. A complementary hypothesis is that variation in neuroanatomical measures in individuals at psychosis risk may be nested within the range observed in healthy individuals. Objective: To quantify deviations from the normative range of neuroanatomical variation in individuals at clinical high risk for psychosis (CHR-P) and evaluate their overlap with healthy variation and their association with positive symptoms, cognition, and conversion to a psychotic disorder. Design, Setting, and Participants: This case-control study used clinical-, IQ-, and neuroimaging software (FreeSurfer)-derived regional measures of cortical thickness (CT), cortical surface area (SA), and subcortical volume (SV) from 1340 individuals with CHR-P and 1237 healthy individuals pooled from 29 international sites participating in the Enhancing Neuroimaging Genetics Through Meta-analysis (ENIGMA) Clinical High Risk for Psychosis Working Group. Healthy individuals and individuals with CHR-P were matched on age and sex within each recruitment site. Data were analyzed between September 1, 2021, and November 30, 2022. Main Outcomes and Measures: For each regional morphometric measure, deviation scores were computed as z scores indexing the degree of deviation from their normative means from a healthy reference population. Average deviation scores (ADS) were also calculated for regional CT, SA, and SV measures and globally across all measures. Regression analyses quantified the association of deviation scores with clinical severity and cognition, and 2-proportion z tests identified case-control differences in the proportion of individuals with infranormal (z < -1.96) or supranormal (z > 1.96) scores. Results: Among 1340 individuals with CHR-P, 709 (52.91%) were male, and the mean (SD) age was 20.75 (4.74) years. Among 1237 healthy individuals, 684 (55.30%) were male, and the mean (SD) age was 22.32 (4.95) years. Individuals with CHR-P and healthy individuals overlapped in the distributions of the observed values, regional z scores, and all ADS values. For any given region, the proportion of individuals with CHR-P who had infranormal or supranormal values was low (up to 153 individuals [<11.42%]) and similar to that of healthy individuals (<115 individuals [<9.30%]). Individuals with CHR-P who converted to a psychotic disorder had a higher percentage of infranormal values in temporal regions compared with those who did not convert (7.01% vs 1.38%) and healthy individuals (5.10% vs 0.89%). In the CHR-P group, only the ADS SA was associated with positive symptoms (ß = -0.08; 95% CI, -0.13 to -0.02; P = .02 for false discovery rate) and IQ (ß = 0.09; 95% CI, 0.02-0.15; P = .02 for false discovery rate). Conclusions and Relevance: In this case-control study, findings suggest that macroscale neuromorphometric measures may not provide an adequate explanation of psychosis risk.

Reduced anterior callosal white matter in risk for psychosis associated with processing speed as a fundamental cognitive impairment.

BACKGROUND: Previous research in psychotic disorders discovered associations between reduced integrity of white matter (WM) in the corpus callosum (CC) and impaired cognitive functions, suggesting processing speed as a central construct. However, it is still largely unexplored to what extent disruption in callosal WM is related to cognitive deficits during the risk stage prior to psychosis. METHODS: To address this gap, we measured the WM integrity in CC by fractional anisotropy (FA) and assessed cognition in 60 clinical-high risk for psychosis (CHR) patients during adolescence/young adulthood and 38 healthy control (HC) subjects. We employed tract based spatial statistics to examine group differences and associations between CC-FA and processing speed, executive function, and spatial working memory. RESULTS: We revealed deficits in processing speed, executive function, and spatial working memory of CHR patients, and reductions in FA of the genu and the body of the CC (p < 0.05, corrected for multiple comparisons) compared to HC. A mediation analysis using the combined sample (CHR + HC) showed that processing speed mediates the associations between the impaired CC structure and executive function and spatial working memory, respectively. Exploratory analyses between CC-FA and the cognitive domains located associations of processing speed in the genu and the body of CC with distinct spatial distributions of executive function and spatial working memory. CONCLUSION: We suggest processing speed as a subordinate cognitive factor contributing to the associations between callosal WM, executive function and working memory. These results extend findings in psychotic disorders to the prior risk stage.

EEG microstate D as psychosis-specific correlate in adolescents and young adults with clinical high risk for psychosis and first-episode psychosis.

Resting-state electroencephalography (EEG) microstates are brief periods (60-120 ms) of quasi-stable scalp field potentials, indicating simultaneous activity of large-scale networks. Microstates are assumed to reflect basic neuronal information processing. A common finding in psychosis spectrum disorders is that microstates classes C and D are altered. Whereas evidence in adults with schizophrenia is substantial, little is known about effects in underage patients, particularly in those at clinical high risk for psychosis (CHR) and first-episode psychosis (FEP). The present study used 74-channel EEG to investigate microstate effects in a large sample of patients with CHR (n = 100) and FEP (n = 33), clinical controls (CC, n = 18), as well as age-matched healthy controls (HC, n = 68). Subjects span an age range from 9 to 35 years, thus, covering underage patients as well as the most vulnerable period for the emergence of psychosis and its prodrome. Four EEG microstates classes were analyzed (A-D). In class D, CHR and FEP patients showed a decrease compared to HC, and CHR patients also to CC. An increase in class C was found in CHR and FEP compared to HC but not to CC. Results were independent of age and no differences were found between the psychosis spectrum groups. The findings suggest an age-independent decrease of microstate class D to be specific to the psychosis spectrum, whereas the increase in class C seems to reflect unspecific psychopathology. Overall, present data strengthens the role of microstate D as potential biomarker for psychosis, as early as in adolescence and already in CHR status.

Exploring the complex relationships between coping strategies, locus of control and self-esteem with psychopathology: structural equation modeling with a special focus on clinical high-risk of psychosis.

BACKGROUND: Coping strategies, competence, and locus of control (LOC) beliefs are important predictors of mental health (MH). However, research into their complex interactions has produced mixed results. Our study investigated them further in the previously unexplored context of clinical high-risk (CHR) of psychosis. METHODS: We tested six alternative structural equation models in a community sample (N = 523), hypothesizing a mediating role of coping and treating CHR symptoms as (i) an additional mediator or (ii) a specific outcome. Our measurement model included two latent factors of MH: (1) psychopathology (PP), consisting of presence of mental disorders, global and psychosocial functioning, and (2) self-rated health (SRH) status. RESULTS: In the model with the best Akaike Information Criterion and the latent factors as outcome variables, maladaptive coping completely mediated the impact of maladaptive LOC on PP and SRH. Additionally, CHR symptoms partially mediated the effect of maladaptive coping on PP and SRH in the community sample, as long as sex was not entered into the model. In the clinical sample (N = 371), the model did not support a mediation by CHR symptoms, despite significant pathways with both coping and MH outcomes; further, competence beliefs directly impacted SRH. CONCLUSIONS: Coping strategies are an important intervention target for MH promotion, especially in the community. In clinical populations, interventions focusing on coping strategies may improve CHR symptoms, thus potentially supporting better MH, especially SRH. Additionally, due to their mostly cascading effects on MH, improving competence and LOC beliefs may also promote psychological well-being.

The role of mentalizing in the relationship between schizotypal personality traits and state signs of psychosis risk captured by cognitive and perceptive basic symptoms.

Objective: Schizotypal traits and disturbances in mentalizing (the capacity to understand the mental states driving one's own and others' behaviors) have been implicated in increased vulnerability for psychosis. Therefore, we explored the associations linking schizotypal traits, mentalizing difficulties and their interactions to clinical high-risk for psychosis (CHR-P), as captured by the Basic Symptoms (BS) approach, during adolescence and young adulthood. Methods: Eighty-seven adolescents and young adults from the general population (46% male, 44% female; age: 14-23 years) were assessed with the Schizophrenia Proneness Interview (SPI-CY/A) for 11 perceptive and cognitive BS, with the Schizotypal Personality Questionnaire (SPQ) for schizotypal traits, and with the Reflective Functioning Questionnaire (RFQ) for self-reported mentalizing abilities. The RFQ evaluates the level of certainty (RFQc scale) and uncertainty (RFQu scale) with which individuals use mental state information to explain their own and others' behaviors. Results: Logistic regression models showed significant positive effects of the SPQ disorganization scale on perceptive BS and of the SPQ interpersonal scale on cognitive BS. Post-hoc analyses revealed that schizotypal features pertaining to odd speech and social anxiety, respectively, were associated with perceptive and cognitive BS. Furthermore, higher scores on the RFQu scale and lower scores on the RFQc scale independently explained the presence of cognitive BS. Finally, significant interaction effects between RFQc and SPQ odd speech on perceptive BS, and between RFQc and SPQ social anxiety on cognitive BS were found. Conclusion: Our findings suggest that schizotypal traits and mentalizing significantly relate both independently and through their interactions to the presence of cognitive and perceptive BS included in CHR-P criteria. Furthermore, mentalizing dysfunction may contribute in the relation between schizotypal traits and early state signs of CHR-P. Mentalizing may support both detection and early treatment of CHR-P among adolescents and young adults who present with trait risk for psychosis.

Neighbourhood characteristics and the treated incidence rate of borderline personality pathology among young people.

OBJECTIVE: The impact of the wider social environment, such as neighbourhood characteristics, has not been examined in the development of borderline personality disorder. This study aimed to determine whether the treated incidence rate of full-threshold borderline personality disorder and sub-threshold borderline personality disorder, collectively termed borderline personality pathology, was associated with the specific neighbourhood characteristics of social deprivation and social fragmentation. METHOD: This study included young people, aged 15-24 years, who attended Orygen's Helping Young People Early programme, a specialist early intervention service for young people with borderline personality pathology, from 1 August 2000-1 February 2008. Diagnoses were confirmed using the Structured Clinical Interview for DSM-IV Personality Disorders, and census data from 2006 were used to determine the at-risk population and to obtain measures of social deprivation and fragmentation. RESULTS: The study included 282 young people, of these 78.0% (n = 220) were female and the mean age was 18.3 years (SD = ±2.7). A total of 42.9% (n = 121) met criteria for full-threshold borderline personality disorder, and 57.1% (n = 161) had sub-threshold borderline personality disorder, defined as having three or four of the nine Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV) borderline personality disorder criteria. There was more than a sixfold increase in the treated incidence rate of borderline personality pathology in the neighbourhoods of above average deprivation (Quartile 3) (incidence rate ratio = 6.45, 95% confidence interval: [4.62, 8.98], p < 0.001), and this was consistent in the borderline personality disorder sub-groups. This association was also present in the most socially deprived neighbourhood (Quartile 4) (incidence rate ratio = 1.63, 95% confidence interval: [1.10, 2.44]), however, only for those with sub-threshold borderline personality disorder. The treated incidence of borderline personality pathology increased incrementally with the level of social fragmentation (Quartile 3: incidence rate ratio = 1.93, 95% confidence interval: [1.37, 2.72], Quartile 4: incidence rate ratio = 2.38, 95% confidence interval: [1.77, 3.21]). CONCLUSION: Borderline personality pathology has a higher treated incidence in the more socially deprived and fragmented neighbourhoods. These findings have implications for funding and location of clinical services for young people with borderline personality pathology. Prospective, longitudinal studies should examine neighbourhood characteristics as potential aetiological factors for borderline personality pathology.

Normative modeling of brain morphometry in Clinical High-Risk for Psychosis.

Importance: The lack of robust neuroanatomical markers of psychosis risk has been traditionally attributed to heterogeneity. A complementary hypothesis is that variation in neuroanatomical measures in the majority of individuals at psychosis risk may be nested within the range observed in healthy individuals. Objective: To quantify deviations from the normative range of neuroanatomical variation in individuals at clinical high-risk for psychosis (CHR-P) and evaluate their overlap with healthy variation and their association with positive symptoms, cognition, and conversion to a psychotic disorder. Design Setting and Participants: Clinical, IQ and FreeSurfer-derived regional measures of cortical thickness (CT), cortical surface area (SA), and subcortical volume (SV) from 1,340 CHR-P individuals [47.09% female; mean age: 20.75 (4.74) years] and 1,237 healthy individuals [44.70% female; mean age: 22.32 (4.95) years] from 29 international sites participating in the ENIGMA Clinical High Risk for Psychosis Working Group. Main Outcomes and Measures: For each regional morphometric measure, z-scores were computed that index the degree of deviation from the normative means of that measure in a healthy reference population (N=37,407). Average deviation scores (ADS) for CT, SA, SV, and globally across all measures (G) were generated by averaging the respective regional z-scores. Regression analyses were used to quantify the association of deviation scores with clinical severity and cognition and two-proportion z-tests to identify case-control differences in the proportion of individuals with infranormal (z<-1.96) or supranormal (z>1.96) scores. Results: CHR-P and healthy individuals overlapped in the distributions of the observed values, regional z-scores, and all ADS vales. The proportion of CHR-P individuals with infranormal or supranormal values in any metric was low (<12%) and similar to that of healthy individuals. CHR-P individuals who converted to psychosis compared to those who did not convert had a higher percentage of infranormal values in temporal regions (5-7% vs 0.9-1.4%). In the CHR-P group, only the ADSSA showed significant but weak associations (|ß|<0.09; PFDR<0.05) with positive symptoms and IQ. Conclusions and Relevance: The study findings challenge the usefulness of macroscale neuromorphometric measures as diagnostic biomarkers of psychosis risk and suggest that such measures do not provide an adequate explanation for psychosis risk.

The impact of school-based screening on service use in adolescents at risk for mental health problems and risk-behaviour.

Early detection and intervention can counteract mental disorders and risk behaviours among adolescents. However, help-seeking rates are low. School-based screenings are a promising tool to detect adolescents at risk for mental problems and to improve help-seeking behaviour. We assessed associations between the intervention "Screening by Professionals" (ProfScreen) and the use of mental health services and at-risk state at 12 month follow-up compared to a control group. School students (aged 15 ± 0.9 years) from 11 European countries participating in the "Saving and Empowering Young Lives in Europe" (SEYLE) study completed a self-report questionnaire on mental health problems and risk behaviours. ProfScreen students considered "at-risk" for mental illness or risk behaviour based on the screening were invited for a clinical interview with a mental health professional and, if necessary, referred for subsequent treatment. At follow-up, students completed another self-report, additionally reporting on service use. Of the total sample (N = 4,172), 61.9% were considered at-risk. 40.7% of the ProfScreen at-risk participants invited for the clinical interview attended the interview, and 10.1% of subsequently referred ProfScreen participants engaged in professional treatment. There were no differences between the ProfScreen and control group regarding follow-up service use and at-risk state. Attending the ProfScreen interview was positively associated with follow-up service use (OR = 1.783, 95% CI = 1.038-3.064), but had no effect on follow-up at-risk state. Service use rates of professional care as well as of the ProfScreen intervention itself were low. Future school-based interventions targeting help-seeking need to address barriers to intervention adherence.Clinical Trials Registration: The trial is registered at the US National Institute of Health (NIH) clinical trial registry (NCT00906620, registered on 21 May, 2009), and the German Clinical Trials Register (DRKS00000214, registered on 27 October, 2009).

Psychometric properties of the Kessler psychological scales in a Swiss young-adult community sample indicate poor suitability for community screening for mental disorders.

AIM: The Kessler psychological distress scales (K10 and K6) are used as screening tools to assess psychological distress related to the likely presence of a mental disorder. Thus, we studied the psychometric properties of their German versions in a Swiss community sample to evaluate their potential usefulness to screen for mental disorders or relevant mental problems in the community and, relatedly, for low threshold transdiagnostic German-speaking services. METHODS: The sample consisted of 829 citizens of the Swiss canton Bern of age 19-43 years. K10/K6 were validated against mini-international neuropsychiatric interview (M.I.N.I.) diagnoses, questionnaires about health status and quality of life. Receiver operating characteristic (ROC) curve analyses were used to test for general discriminative ability and to select optimal cut-offs of the K10 and K6 for non-psychotic full-blown and subthreshold mental disorders. RESULTS: Cronbach's alphas were 0.81 (K10) and 0.70 (K6). ROC analyses indicated much lower optimal thresholds than earlier suggested; 10 for K10 and 6 for K6. At these thresholds, against M.I.N.I. diagnoses, Cohen's κ (≤0.173) and correspondence rates (≤58.14%) were insufficient throughout. Values were higher at the earlier suggested threshold, yet, at the cost of sensitivity that was below 0.5 in all but three, and below 0.3 in all but six cases. CONCLUSIONS: For the lack of sufficient validity and sensitivity, respectively, our findings suggest that both K10 and K6 would only be of limited use in a low-threshold transdiagnostic mental health service for young adults in Switzerland and likely other German-speaking countries.

Childhood Maltreatment and Its Association with Cognitive Ability in Young People Suspected to Be at Clinical High Risk of Psychosis.

INTRODUCTION: Childhood maltreatment is associated with both reduced cognitive functioning and the development of psychotic symptoms. However, the specific relationship between childhood maltreatment, cognitive abilities and (pre)psychotic symptoms remains unclear. Therefore, the aim of this study was to investigate the association between childhood maltreatment and tasks of verbal memory and processing speed in a help-seeking sample of an early detection of psychosis service. METHODS: A total of 274 participants consisting of 177 clinical high risk (CHR) for psychosis subjects and 97 clinical controls (CC) with subthreshold CHR underwent a battery of neurocognitive assessments measuring the latent variables verbal memory and processing speed. Additionally, the Trauma and Distress Scale (TADS) was administered to assess varying childhood maltreatment subtypes. Structural equation modeling (SEM) was used to examine associations between verbal memory, processing speed, and maltreatment subtypes. Other factors in the model were age, gender, clinical group (CHR or CC), and the presence of different CHR criteria. RESULTS: Physical abuse was associated with lower scores in verbal memory and processing speed. The explained variance in the SEM reached up to 9.5% for verbal memory and 24.9% for processing speed. Both latent variables were each associated with the presence of cognitive-perceptive basic symptoms. Lower verbal memory was additionally associated with the clinical high-risk group, and processing speed capacity was associated with higher age and female gender. CONCLUSION: Childhood physical abuse in particular was associated with poorer performance on verbal memory and processing speed across both groups of CHR and CC with subthreshold CHR symptoms. This adds to the current literature on reduced cognitive abilities when childhood maltreatment had occurred, albeit subtype dependent. Our findings, together with high prevalence rates of childhood maltreatment in patients with psychosis or CHR states, along with the presence of cognitive deficits in these patients, highlight the importance of not only assessing cognition but also childhood maltreatment in managing these patients. Future research should investigate the specific biological mechanisms of childhood maltreatment on verbal memory and processing speed in CHR subjects, as neurobiological alterations might explain the underlying mechanisms.

[Positive Psychotic Symptoms in Childhood and Adolescence]. / Positiv psychotische Symptome in Kindheit und Jugend.

In both classification systems, DSM-5 and ICD-11, the diagnostic criteria of schizophreniaspectrum disorders in minors are identical to those of adults. Nevertheless, recent studies have emphasized important differences in phenomenology and clinical impact of positive psychotic symptoms between children, adolescents and young adults. Among positive psychotic symptoms, hallucinations have a high prevalence in childhood, where they are often described as vivid, multisensory experiences, that mostly remit spontaneously. In children, these symptoms are not necessarily associated with the emergence of schizophrenia-spectrum disorders. However, they can indicate comorbid psychiatric disorders and cause significant stress or, in other cases, be transient symptoms without any significant pathological value. The article provides a review on recent epidemiological and phenomenological findings on positive psychotic symptoms in children and adolescents and proposes diagnostic and therapeutic strategies on the management of these symptoms in minors.

Neuroanatomical heterogeneity and homogeneity in individuals at clinical high risk for psychosis.

Individuals at Clinical High Risk for Psychosis (CHR-P) demonstrate heterogeneity in clinical profiles and outcome features. However, the extent of neuroanatomical heterogeneity in the CHR-P state is largely undetermined. We aimed to quantify the neuroanatomical heterogeneity in structural magnetic resonance imaging measures of cortical surface area (SA), cortical thickness (CT), subcortical volume (SV), and intracranial volume (ICV) in CHR-P individuals compared with healthy controls (HC), and in relation to subsequent transition to a first episode of psychosis. The ENIGMA CHR-P consortium applied a harmonised analysis to neuroimaging data across 29 international sites, including 1579 CHR-P individuals and 1243 HC, offering the largest pooled CHR-P neuroimaging dataset to date. Regional heterogeneity was indexed with the Variability Ratio (VR) and Coefficient of Variation (CV) ratio applied at the group level. Personalised estimates of heterogeneity of SA, CT and SV brain profiles were indexed with the novel Person-Based Similarity Index (PBSI), with two complementary applications. First, to assess the extent of within-diagnosis similarity or divergence of neuroanatomical profiles between individuals. Second, using a normative modelling approach, to assess the 'normativeness' of neuroanatomical profiles in individuals at CHR-P. CHR-P individuals demonstrated no greater regional heterogeneity after applying FDR corrections. However, PBSI scores indicated significantly greater neuroanatomical divergence in global SA, CT and SV profiles in CHR-P individuals compared with HC. Normative PBSI analysis identified 11 CHR-P individuals (0.70%) with marked deviation (>1.5 SD) in SA, 118 (7.47%) in CT and 161 (10.20%) in SV. Psychosis transition was not significantly associated with any measure of heterogeneity. Overall, our examination of neuroanatomical heterogeneity within the CHR-P state indicated greater divergence in neuroanatomical profiles at an individual level, irrespective of psychosis conversion. Further large-scale investigations are required of those who demonstrate marked deviation.

Clinical, Brain, and Multilevel Clustering in Early Psychosis and Affective Stages.

Importance: Approaches are needed to stratify individuals in early psychosis stages beyond positive symptom severity to investigate specificity related to affective and normative variation and to validate solutions with premorbid, longitudinal, and genetic risk measures. Objective: To use machine learning techniques to cluster, compare, and combine subgroup solutions using clinical and brain structural imaging data from early psychosis and depression stages. Design, Setting, and Participants: A multisite, naturalistic, longitudinal cohort study (10 sites in 5 European countries; including major follow-up intervals at 9 and 18 months) with a referred patient sample of those with clinical high risk for psychosis (CHR-P), recent-onset psychosis (ROP), recent-onset depression (ROD), and healthy controls were recruited between February 1, 2014, to July 1, 2019. Data were analyzed between January 2020 and January 2022. Main Outcomes and Measures: A nonnegative matrix factorization technique separately decomposed clinical (287 variables) and parcellated brain structural volume (204 gray, white, and cerebrospinal fluid regions) data across CHR-P, ROP, ROD, and healthy controls study groups. Stability criteria determined cluster number using nested cross-validation. Validation targets were compared across subgroup solutions (premorbid, longitudinal, and schizophrenia polygenic risk scores). Multiclass supervised machine learning produced a transferable solution to the validation sample. Results: There were a total of 749 individuals in the discovery group and 610 individuals in the validation group. Individuals included those with CHR-P (n = 287), ROP (n = 323), ROD (n = 285), and healthy controls (n = 464), The mean (SD) age was 25.1 (5.9) years, and 702 (51.7%) were female. A clinical 4-dimensional solution separated individuals based on positive symptoms, negative symptoms, depression, and functioning, demonstrating associations with all validation targets. Brain clustering revealed a subgroup with distributed brain volume reductions associated with negative symptoms, reduced performance IQ, and increased schizophrenia polygenic risk scores. Multilevel results distinguished between normative and illness-related brain differences. Subgroup results were largely validated in the external sample. Conclusions and Relevance: The results of this longitudinal cohort study provide stratifications beyond the expression of positive symptoms that cut across illness stages and diagnoses. Clinical results suggest the importance of negative symptoms, depression, and functioning. Brain results suggest substantial overlap across illness stages and normative variation, which may highlight a vulnerability signature independent from specific presentations. Premorbid, longitudinal, and genetic risk validation suggested clinical importance of the subgroups to preventive treatments.

Clinical high-risk criteria of psychosis in 8-17-year-old community subjects and inpatients not suspected of developing psychosis.

BACKGROUND: In children and adolescents compared to adults, clinical high-risk of psychosis (CHR) criteria and symptoms are more prevalent but less psychosis-predictive and less clinically relevant. Based on high rates of non-converters to psychosis, especially in children and adolescents, it was suggested that CHR criteria were: (1) Pluripotential; (2) A transdiagnostic risk factor; and (3) Simply a severity marker of mental disorders rather than specifically psychosis-predictive. If any of these three alternative explanatory models were true, their prevalence should differ between persons with and without mental disorders, and their severity should be associated with functional impairment as a measure of severity. AIM: To compare the prevalence and severity of CHR criteria/symptoms in children and adolescents of the community and inpatients. METHODS: In the mainly cross-sectional examinations, 8-17-year-old community subjects (n = 233) randomly chosen from the population register of the Swiss Canton Bern, and inpatients (n = 306) with primary diagnosis of attention-deficit/hyperactivity disorder (n = 86), eating disorder (n = 97), anxiety including obsessive-compulsive disorder (n = 94), or autism spectrum disorder (n = 29), not clinically suspected to develop psychosis, were examined for CHR symptoms/criteria. Positive items of the Structured Interview for Psychosis-Risk Syndromes (SIPS) were used to assess the symptomatic ultra-high-risk criteria, and the Schizophrenia Proneness Instrument, Child and Youth version (SPI-CY) was used to assess the 14 basic symptoms relevant to basic symptom criteria. We examined group differences in frequency and severity of CHR symptoms/criteria using χ 2 tests and nonparametric tests with Cramer's V and Rosenthal's r as effect sizes, and their association with functioning using correlation analyses. RESULTS: The 7.3% prevalence rate of CHR criteria in community subjects did not differ significantly from the 9.5% rate in inpatients. Frequency and severity of CHR criteria never differed between the community and the four inpatient groups, while the frequency and severity of CHR symptoms differed only minimally. Group differences were found in only four CHR symptoms: suspiciousness/persecutory ideas of the SIPS [χ 2 (4) = 9.425; P = 0.051, Cramer's V = 0.132; and Z = -4.281, P < 0.001; Rosenthal's r = 0.184], and thought pressure [χ 2 (4) = 11.019; P = 0.026, Cramer's V = 0.143; and Z = -2.639, P = 0.008; Rosenthal's r = 0.114], derealization [χ 2 (4) = 32.380; P < 0.001, Cramer's V = 0.245; and Z = -3.924, P < 0.001; Rosenthal's r = 0.169] and visual perception disturbances [χ 2 (4) = 10.652; P = 0.031, Cramer's V = 0.141; and Z = -2.822, P = 0.005; Rosenthal's r = 0.122] of the SPI-CY. These were consistent with a transdiagnostic risk factor or dimension, i.e., displayed higher frequency and severity in inpatients, in particular in those with eating, anxiety/obsessive-compulsive and autism spectrum disorders. Low functioning, however, was at most weakly related to the severity of CHR criteria/symptoms, with the highest correlation yielded for suspiciousness/persecutory ideas (Kendall's tau = -0.172, P < 0.001). CONCLUSION: The lack of systematic differences between inpatients and community subjects does not support suggestions that CHR criteria/symptoms are pluripotential or transdiagnostic syndromes, or merely markers of symptom severity.

Positive psychotic symptoms in childhood and adolescence.

Based on the assumption of a universal neurodevelopmental model of psychosis, especially of the schizophrenia spectrum, the diagnosis (and treatment) of psychosis in minors commonly follows those in adults. Yet, as our review demonstrates, recent years have seen an emergence of studies of minors indicating that developmental aspects may play a crucial role in the prevalence and appraisal of diagnostically relevant positive psychotic symptoms in their full-blown and subthreshold forms, including neurobiogenetic and other risk factors, such as migration. Thus, caution is advised to not overpathologize potentially transient and clinically irrelevant occurrence of (subthreshold) positive psychotic symptoms in the diagnosis and treatment of psychotic disorders and their clinical high-risk states in minors. More studies on developmental aspects are urgently needed.

The Important Role of Stereotypes in the relation between Mental Health Literacy and Stigmatization of Depression and Psychosis in the Community.

Increased mental health literacy (MHL) has not reduced stigmatization of people with mental disorder. Thus, we examined the role of stereotypes in the interplay of MHL (correct labelling, causal explanations) and the wish for social distance (WSD) from people with depressive and psychotic symptoms in a community sample of 1526 German-speaking participants in the Swiss 'Bern Epidemiological At-Risk' study (age 16-40 years; response rate: 60.1%). Following the presentation of an unlabelled case vignette of depression or psychosis, MHL, stereotypes and WSD were assessed in a questionnaire survey. Their interrelations were studied using structural equation modelling. MHL was not directly linked to WSD, only the psychosocial causal model was directly negatively associated with WSD. Perceived dangerousness particularly increased WSD, this was increased by a biogenetic causal model and decreased by a psychosocial causal model. Awareness-campaigns that, next to biological causes, emphasize psychosocial causes of mental disorders might better reduce stigmatization.

The Bern Early Recognition and Intervention Centre for mental crisis (FETZ Bern)-An 8-year evaluation.

AIM: Early detection of, and intervention for, psychosis during its prodromal phase has the potential to alter the course of the disease and has therefore become a major objective of modern clinical psychiatry. An increasing number of early detection and intervention services have been established in Europe and worldwide. This study aims to describe and evaluate an early detection and intervention service for children, adolescents and adults (FETZ Bern) aged from eight to 40 years with a population catchment area of 1.035 million in Bern, Switzerland. METHODS: Routine demographic, diagnostic and service usage data were collected upon admission to the service. Using a retrospective, descriptive and naturalistic study design, data was analysed for different age groups (children, adolescents and adults) and where available, outcome data after 12 and 24 months was evaluated. RESULTS: The FETZ Bern has received 827 referrals with full diagnostic data available for 353 patients. The majority of the assessed patients were young males. While 40% met criteria for a clinical high-risk state of psychosis, 20% were diagnosed with fully manifest psychosis at time of admission, and another 40% had one or more non-psychotic axis-I diagnoses. CONCLUSIONS: The FETZ Bern is the first early detection centre worldwide assessing children aged younger than 12 years, as well as adolescents and young adults in one service. Given that developmental peculiarities are important in understanding and ultimately treating psychosis, the FETZ Bern, with its emphasis on developmental peculiarities, should be considered as a model for other similar services.

Introducing a Group Therapy Program (PLAN D) for Young Outpatients with Derealization and Depersonalization: A Pilot Study.

Depersonalization and derealization (DD) cause significant distress and are associated with poor role and social functional outcomes. Despite the relatively high prevalence of DD symptoms and the chronic course in those suffering from a DD disorder, there still exists a need for effective interventions. Preliminary evidence indicates that cognitive behavioral therapy (CBT) delivered in an individual setting demonstrates some positive intervention effects for patients with DD regarding their symptom levels. By considering DD-specific treatment needs, a group therapy program was developed as an add-on therapy based on CBT techniques called PLAN D comprising the following elements: psychoeducation, lifestyle interventions, acceptance and mindfulness training, and new patterns of DD-related cognitions. In a pilot study, we present an 8-week group intervention for adolescents and young adults with DD disorder. To our knowledge, no standardized group intervention program for DD exists so far. Thus, this novel intervention represents a promising opportunity to positively influence long-term outcomes and course of DD.