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.

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.

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).

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.

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.

[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.

Basic symptoms and gray matter volumes of patients at clinical high risk for psychosis.

BACKGROUND: Clinical high-risk (CHR) for psychosis is indicated by ultra-high risk (UHR) and basic symptom (BS) criteria; however, conversion rates are highest when both UHR and BS criteria are fulfilled (UHR&BS). While BSs are considered the most immediate expression of neurobiological aberrations underlying the development of psychosis, research on neurobiological correlates of BS is scarce. METHODS: We investigated gray matter volumes (GMV) of 20 regions of interest (ROI) previously associated with UHR criteria in 90 patients from the Bern early detection service: clinical controls (CC), first-episode psychosis (FEP), UHR, BS and UHR&BS. We expected lowest GMV in FEP and UHR&BS, and highest volume in CC with UHR and BS in-between. RESULTS: Significantly, lower GMV was detected in FEP and UHR&BS patients relative to CC with no other significant between-group differences. When ROIs were analyzed separately, seven showed a significant group effect (FDR corrected), with five (inferior parietal, medial orbitofrontal, lateral occipital, middle temporal, precuneus) showing significantly lower GM volume in the FEP and/or UHR&BS groups than in the CC group (Bonferroni corrected). In the CHR group, only COGDIS scores correlated negatively with cortical volumes. CONCLUSIONS: This is the first study to demonstrate that patients who fulfill both UHR and BS criteria - a population that has been associated with higher conversion rates - exhibit more severe GMV reductions relative to those who satisfy BS or UHR criteria alone. This result was mediated by the BS in the UHR&BS group, as only the severity of BS was linked to GMV reductions.

Predictors of help-seeking behaviour in people with mental health problems: a 3-year prospective community study.

BACKGROUND: The majority of people with mental illness do not seek help at all or only with significant delay. To reduce help-seeking barriers for people with mental illness, it is therefore important to understand factors predicting help-seeking. Thus, we prospectively examined potential predictors of help-seeking behaviour among people with mental health problems (N = 307) over 3 years. METHODS: Of the participants of a 3-year follow-up of a larger community study (response rate: 66.4%), data of 307 (56.6%) persons with any mental health problems (age-at-baseline: 16-40 years) entered a structural equation model of the influence of help-seeking, stigma, help-seeking attitudes, functional impairments, age and sex at baseline on subsequent help-seeking for mental health problems. RESULTS: Functional impairment at baseline was the strongest predictor of follow-up help-seeking in the model. Help-seeking at baseline was the second-strongest predictor of subsequent help-seeking, which was less likely when help-seeking for mental health problems was assumed to be embarrassing. Personal and perceived stigma, and help-seeking intentions had no direct effect on help-seeking. CONCLUSIONS: With only 22.5% of persons with mental health problems seeking any help for these, there was a clear treatment gap. Functional deficits were the strongest mediator of help-seeking, indicating that help is only sought when mental health problems have become more severe. Earlier help-seeking seemed to be mostly impeded by anticipated stigma towards help-seeking for mental health problems. Thus, factors or beliefs conveying such anticipated stigma should be studied longitudinally in more detail to be able to establish low-threshold services in future.

[Psychotic disorders in ICD-11: the revisions]. / Psychotische Störungen in der ICD-11: Die Revisionen.

Psychotic disorders in ICD-11: the revisions Abstract. This article provides an overview of the main changes to the chapter "Schizophrenia or Other Primary Psychotic Disorders" (6A2) from ICD-10 to ICD-11 and compares them with the psychosis chapter of DSM-5. These changes include abandoning the classical subtypes of Schizophrenia as well as of the special significance of Schneider's first-rank symptoms, resulting in the general requirement of two key features (one must be a positive symptom) in the definition of "Schizophrenia" (6A20) and the allowance for bizarre contents in "Delusional Disorder" (6A24), which now includes "Induced Delusional Disorder" (F24). Further introduced are the focus on the current episode, the restriction of "Acute and Transient Psychotic Disorder" (6A23) to the former Polymorphic Disorder Without Schizophrenic Symptoms (F23.0), the diagnosis of delusional "Obsessive-Compulsive or Related Disorders" (6B2) exclusively as Obsessive-Compulsive Disorders, the specification of "Schizoaffective Disorder" (6A21), and the formulation of a distinct subchapter "Catatonia" (6A4) for the assessment of catatonic features in the context of several disorders. In analogy to DSM-5, ICD-11 now includes the optional category "Symptomatic Manifestations of Primary Psychotic Disorders" (6A25) for the dimensional quantification of symptoms. Again, developmental aspects remain unattended in in the ICD-11-definitions of psychotic disorders.

Age effects on basic symptoms in the community: A route to gain new insight into the neurodevelopment of psychosis?

Reports of limited clinical significance of attenuated psychotic symptoms before age 15/16 indicate an important role of neurodevelopment in the early detection of psychoses. Therefore, we examined if age also exerts an influence on the prevalence and clinical significance of the 14 cognitive and perceptive basic symptoms (BS) used in psychosis-risk criteria and conceptualized as the most direct self-experienced expression of neurobiological aberrations. A random representative general population sample of the Swiss canton Bern (N = 689, age 8-40 years, 06/2011-05/2014) was interviewed for BS, psychosocial functioning, and current mental disorder. BS were reported by 18% of participants, mainly cognitive BS (15%). In regression analyses, age affected perceptive and cognitive BS differently, indicating an age threshold for perceptive BS in late adolescence (around age 18) and for cognitive BS in young adulthood (early twenties)-with higher prevalence, but a lesser association with functional deficits and the presence of mental disorder in the below-threshold groups. Thereby, interaction effects between age and BS on functioning and mental disorder were commonly stronger than individual effects of age and BS. Indicating support of the proposed "substrate-closeness" of BS, differential age effects of perceptual and cognitive BS seem to follow normal brain maturation processes, in which they might occur as infrequent and temporary non-pathological disturbances. Their persistence or occurrence after conclusion of main brain maturation processes, however, might signify aberrant maturation or neurodegenerative processes. Thus, BS might provide important insight into the pathogenesis of psychosis and into differential neuroprotective or anti-inflammatory targets.

Prevalence and clinical relevance of interview-assessed psychosis-risk symptoms in the young adult community.

BACKGROUND: An efficient indicated prevention of psychotic disorders requires valid risk criteria that work in both clinical and community samples. Yet, ultra-high risk and basic symptom criteria were recently recommended for use in clinical samples only. Their use in the community was discouraged for lack of knowledge about their prevalence, clinical relevance and risk factors in non-clinical, community settings when validly assessed with the same instruments used in the clinic. METHODS: Using semi-structured telephone interviews with established psychosis-risk instruments, we studied the prevalence of psychosis-risk symptoms and criteria, their clinical relevance (using presence of a non-psychotic mental disorder or of functional deficits as proxy measures) and their risk factors in a random, representative young adult community sample (N=2683; age 16-40 years; response rate: 63.4%). RESULTS: The point-prevalence of psychosis-risk symptoms was 13.8%. As these mostly occurred too infrequent to meet frequency requirements of psychosis-risk criteria, only 2.4% of participants met psychosis-risk criteria. A stepwise relationship underlay the association of ultra-high risk and basic symptoms with proxy measures of clinical relevance, this being most significant when both occurred together. In line with models of their formation, basic symptoms were selectively associated with age, ultra-high risk symptoms with traumatic events and lifetime substance misuse. CONCLUSIONS: Psychosis-risk criteria were uncommon, indicating little risk of falsely labelling individuals from the community at-risk for psychosis. Besides, both psychosis-risk symptoms and criteria seem to possess sufficient clinical relevance to warrant their broader attention in clinical practice, especially if ultra-high risk and basic symptoms occur together.

Course of clinical high-risk states for psychosis beyond conversion.

BACKGROUND: The main focus of research on clinical high-risk states for psychosis (CHR) has been the development of algorithms to predict psychosis. Consequently, other outcomes have been neglected, and little is known about the long-term diagnostic and functional outcome among those not converting to psychosis. METHODS: In a naturalistic study, incidence, persistence, and remission rates of CHR states according to symptomatic ultra-high risk or cognitive disturbances criteria were investigated in 160 of 246 outpatients of an early detection of psychoses service (21.1% CHR negative and 78.9% CHR positive at baseline) who had not converted to psychosis within follow-up (median 53.7 months, range 13.9-123.7 months). RESULTS: Remission rate of CHR status was 43.3% of all 194 CHR-positive cases, including converters, or 72.4% if only the 116 non-converters were considered, persistence rate was 27.6%, and new occurrence rate in initially CHR-negative patients was 9.1%. At follow-up, 54.5% of the non-converters met criteria of at least one Axis-I diagnosis, mainly affective and anxiety disorders, and had functional problems. The severity of risk at baseline was not associated with a higher presence of Axis-I diagnosis at follow-up. CONCLUSIONS: During follow-up, CHR symptoms remitted in one-third of initially CHR-positive patients, while almost 10% met CHR criteria newly in CHR-negative adults presenting at early detection services. The presence of CHR criteria seems to maintain the risk for lower functioning and mental disorders, particularly for affective disorders. Thus, therapeutic efforts targeting CHR patients should also focus on the current mental disorders as well as social and role functions to improve the long-term outcome.

What Is the Incidence of Implant Malpositioning and Revision Surgery After Orbital Repair?

PURPOSE: Postoperative radiographic examinations are the gold standard in maxillofacial surgery, except in orbital reconstruction. Therefore, the purpose of this study was to estimate the frequency of implant malposition and revision operation after orbital repair. MATERIALS AND METHODS: This retrospective cohort study was conducted in a level I trauma center at the University Hospital in Bern, Switzerland. To assess the incidence of malpositioning, a qualitative analysis of postoperative computed tomography scans, as well as comparative volumetric measurements of the orbits, was conducted. Furthermore, the incidence of and reason for secondary revision procedures were evaluated. RESULTS: From September 2008 to December 2015, a total of 71 emergency patients (73 implants) were treated at the Department of Cranio-Maxillofacial Surgery with a titanium mesh (48 male patients; mean age, 56 years). The implant position was rated as poor in 17 cases (23%) by the qualitative analysis. The volumetric assessment showed no significant results. Revision intervention was needed in 12 patients (17%) because of an unsuccessful treatment outcome causing relevant clinical symptoms. CONCLUSIONS: Patients with large orbital defects who require surgical treatment with a titanium mesh are at risk of implant malposition. Because in this study, poor positioning of the implant is the main reason for surgical revision, we postulate that a postoperative radiographic control should be obtained routinely. Only then can long-term sequelae due to inadequate reconstruction be avoided.

Age effect on prevalence of ultra-high risk for psychosis symptoms: replication in a clinical sample of an early detection of psychosis service.

Higher frequencies of perceptual and lesser clinical significance of non-perceptual attenuated psychotic symptoms (APS) have been reported by 8- to 15-year-old of the general population compared to 16- to 40-year-old. We examined if such an age-effect can also be detected in a clinical never-psychotic sample (N = 133) referred to a specialized service for clinical suspicion of developing psychosis. APS and brief intermittent psychotic symptoms (BIPS) were assessed using items P1-P3 and P5 (non-perceptual), and P4 (perceptual) of the Structured Interview for Psychosis-Risk Syndromes, current axis-I disorders with the Mini-International Neuropsychiatric Interview, and psychosocial functioning with the Social and Occupational Functioning Assessment Scale. In the sample, 64% reported APS (61%) or BIPS (7%); any perceptual APS/BIPS was reported by 43% and any non-perceptual APS/BIPS by 44%. In correspondence to the results in the general population sample, perceptual but not non-perceptual APS/BIPS were significantly more frequent in younger age groups below the age of 16 (8-12 years: odds ratio (OR) = 4.7 (1.1-19.5); 13-15 years: OR = 2.7 (0.9-7.7); 20-24-year-old as reference group). An age-effect of APS/BIPS on the presence of any current axis-I disorder (59%) or functional difficulties (67%) was not detected. However, when onset requirements of APS criteria (onset/worsening in past year) were met, the likelihood of a psychiatric diagnosis increased significantly with advancing age. Overall, the replicated age-effect on perceptual APS/BIPS in this clinical sample highlights the need to examine ways to distinguish clinically relevant perceptual APS/BIPS from perceptual aberrations likely remitting over the course of adolescence.

Duration of unspecific prodromal and clinical high risk states, and early help-seeking in first-admission psychosis patients.

PURPOSE: Prevention of psychosis requires both presence of clinical high risk (CHR) criteria and early help-seeking. Previous retrospective studies of the duration of untreated illness (i.e. prodrome plus psychosis) did not distinguish between prodromal states with and without CHR symptoms. Therefore, we examined the occurrence of CHR symptoms and first help-seeking, thereby considering effects of age at illness-onset. METHODS: Adult patients first admitted for psychosis (n = 126) were retrospectively assessed for early course of illness and characteristics of first help-seeking. RESULTS: One-hundred and nine patients reported a prodrome, 58 with CHR symptoms. In patients with an early illness-onset before age 18 (n = 45), duration of both illness and psychosis were elongated, and CHR symptoms more frequent (68.9 vs. 33.3 %) compared to those with adult illness-onset. Only 29 patients reported help-seeking in the prodrome; this was mainly self-initiated, especially in patients with an early illness-onset. After the onset of first psychotic symptoms, help-seeking was mainly initiated by others. State- and age-independently, mental health professionals were the main first point-of-call (54.0 %). CONCLUSIONS: Adult first-admission psychosis patients with an early, insidious onset of symptoms before age 18 were more likely to recall CHR symptoms as part of their prodrome. According to current psychosis-risk criteria, these CHR symptoms, in principle, would have allowed the early detection of psychosis. Furthermore, compared to patients with an adult illness-onset, patients with an early illness-onset were also more likely to seek help on their own account. Thus, future awareness strategies to improve CHR detection might be primarily related to young persons and self-perceived subtle symptoms.

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.

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.

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.

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.