Ultra-high Risk Criteria Research Articles

Beyond the "at risk mental state" concept: transitioning to transdiagnostic psychiatry.

The "at risk mental state" for psychosis approach has been a catalytic, highly productive research paradigm over the last 25 years. In this paper we review that paradigm and summarize its key lessons, which include the valence of this phenotype for future psychosis outcomes, but also for comorbid, persistent or incident non-psychotic disorders; and the evidence that onset of psychotic disorder can at least be delayed in ultra high risk (UHR) patients, and that some full-threshold psychotic disorder may emerge from risk states not captured by UHR criteria. The paradigm has also illuminated risk factors and mechanisms involved in psychosis onset. However, findings from this and related paradigms indicate the need to develop new identification and diagnostic strategies. These findings include the high prevalence and impact of mental disorders in young people, the limitations of current diagnostic systems and risk identification approaches, the diffuse and unstable symptom patterns in early stages, and their pluripotent, transdiagnostic trajectories. The approach we have recently adopted has been guided by the clinical staging model and adapts the original "at risk mental state" approach to encompass a broader range of inputs and output target syndromes. This approach is supported by a number of novel modelling and prediction strategies that acknowledge and reflect the dynamic nature of psychopathology, such as dynamical systems theory, network theory, and joint modelling. Importantly, a broader transdiagnostic approach and enhancing specific prediction (profiling or increasing precision) can be achieved concurrently. A holistic strategy can be developed that applies these new prediction approaches, as well as machine learning and iterative probabilistic multimodal models, to a blend of subjective psychological data, physical disturbances (e.g., EEG measures) and biomarkers (e.g., neuroinflammation, neural network abnormalities) acquired through fine-grained sequential or longitudinal assessments. This strategy could ultimately enhance our understanding and ability to predict the onset, early course and evolution of mental ill health, further opening pathways for preventive interventions.

F167. ACCESS, UNDERSTAND, APPRAISE AND APPLY TO / OF HEALTH INFORMATION AND HEALTH LITERACY IN INDIVIDUALS AT-RISK FOR PSYCHOSIS: A SYSTEMATIC REVIEW

BackgroundNumerous studies suggest that health literacy (HL) plays a crucial role in maintaining and improving individual health. Furthermore, empirical findings highlight the relation between levels of a person’s HL and clinical outcomes. So far, there are no reviews, which investigate HL in individuals at-risk for psychosis. The aim of the current review is to assess how individuals at risk of developing a first episode of psychosis gain access to, understand, evaluate and apply risk-related health information.MethodsA mixed-methods approach was used to analyze and synthesize a variety of study types including qualitative and quantitative studies. Search strategy, screening and data selection have been carried out according to the PRISMA criteria. The systematic search was applied on peer-reviewed literature in PUBMED, Cochrane Library, PsycINFO and Web of Science. Studies were included if participants met clinical high risk criteria (CHR), including the basic symptom criterion (BS) and the ultra-high risk (UHR) criteria. The UHR criteria comprise the attenuated psychotic symptom criterion (APS), the brief limited psychotic symptom criterion (BLIPS) and the genetic risk and functional decline criterion (GRDP) Furthermore, studies must have used validated HL measures or any operationalization of the HL’s subdimensions (access, understanding, appraisal, decision-making or action) as a primary outcome. A third inclusion criterion comprised that the concept of HL or one of the four dimensions was mentioned in title or abstract. Data extraction and synthesis was implemented according to existing recommendations for appraising evidence from different study types. The quality of the included studies was evaluated and related to the study results.ResultsThe search string returned 10587 papers. After data extraction 15 quantitative as well as 4 qualitative studies and 3 reviews were included. The Quality assessment evaluated 12 publications as “good”, 9 as “fair” and one paper as “poor”. Only one of the studies assessed HL with as primary outcome. In the other studies, the five different subdimensions of HL were investigated as a secondary outcome respectively mentioned in the paper. “Gaining Access” was examined in 18 of the 22 studies. “Understanding” has been assessed in 7 publications. “Appraise” was examined in 9 studies. “Apply decision making” and “Apply health behavior” were investigated in 1 of 8 studies. Since none of the included publications operationalized neither HL nor the subdimensions of HL with a validated measure, no explicit influencing factors could be found.DiscussionQuantitative and qualitative evidence indicates that subjects at-risk for psychosis describe a lack of understanding about their state and fear stigmatization that might lead to dysfunctional coping strategies, such as ignoring and hiding symptoms. Affected subjects are eager to be informed about their condition and describe favoured channels for obtaining information. The internet, family members, school personnel and GP’s play a crucial role in gain access to, understand, evaluate and apply risk-related health information. The results clearly highlight that more research should be dedicated to HL in individuals at risk of developing a psychosis. Further studies should explore the relation between HL and clinical outcomes in this target population by assessing the underlining constructs with validated tools.

O10.8. A PLURIPOTENTIAL AT RISK MENTAL STATE: INITIAL RESULTS

BackgroundThe development of the ultra-high risk (UHR) criteria for psychosis over 20 years ago created a new framework for research into subthreshold states in psychiatry. Since (i) early clinical phenotypes are overlapping and non-specific, and (ii) prevention research faces the challenge of achieving adequate statistical power when focusing on low incidence syndromes such as schizophrenia, we introduce an extension of the UHR approach in order to encompass trans-diagnostic targets. The ‘CHARMS’ (Clinical High at Risk Mental State) study aims to validate a set of pluripotential criteria to prospectively identify help-seeking young people at risk of developing a range of serious mental disorders.MethodsThe CHARMS study is a cohort study of help-seeking young people aged 12–25 attending youth mental health services in Melbourne, Australia. New referrals meeting the CHARMS criteria are allocated to the CHARMS+ group; referrals under CHARMS threshold are allocated to CHARMS- (control) group. Transition status and clinical/functional outcomes are re-assessed at 6 and 12 months. The CHARMS criteria consist of subthreshold states for psychosis, mania, severe depression and borderline personality disorder. A range of clinical predictors, including anxiety, stress, sleep/circadian disturbance, and cognitive biases are being assessed as well.ResultsTo date, a sample of N=73 participants have been recruited: N=49 (67%) met CHARMS criteria (CHARMS+) at baseline with N=24 (33%) allocations to the control group (CHARMS-). Of these, N=48 participants have been followed up to 6 months and a sample of N=35 has been followed up to 12 months. At 6 months, 32% of the CHARMS+ group have transitioned to a full-threshold mental disorder which increased to 37% at 12 month follow-up. 0% of the CHARMS- control group has transitioned.DiscussionOur initial results indicate that the CHARMS criteria can be applied in the context of a youth mental health service and validly identify help-seeking young people at substantial risk of progressing to serious mental disorder over a short time frame (within 12 months). This study is the first to introduce and validate a set of clinical criteria to identify a broader ‘at risk’ patient population, and represents an important advance from the UHR for psychosis approach. It will foster understanding of risk factors and pathogenic mechanisms that drive the onset of severe mental disorder transdiagnostically and introduce a new case identification paradigm for the next generation of preventive intervention trials.

T9. CROSS-SECTIONAL ASSOCIATION OF MEMBRANE FATTY ACID COMPOSITION AND PSYCHOPATHOLOGY IN THE NEURAPRO-E STUDY

BackgroundConverging evidence suggests that people at ultra-high risk (UHR) for psychosis have depleted levels of several fatty acids (FAs), and that changes in omega-3 (n-3) FA levels may indicate a higher risk for transition to psychosis. However, limited information is available on how FA deficiencies relate to psychopathology in individuals with UHR phenotypes. Here, we report the relationship between membrane FA levels and symptom severity in a study of individuals at UHR for psychosis.MethodsData from 280 of 304 (92%) of participants of the NEURAPRO study, a multi-centre randomized-controlled trial of omega-3 fatty acids versus placebo, were used for the present analysis. All participants were aged between 13 and 40 years and met criteria for UHR for psychosis. Blood samples were collected at study baseline and month 6 (end-of-intervention). Membrane fatty acids were analysed using mass spectrometry as percentage of total fatty acids in erythrocytes. Pearson correlation coefficients were calculated between baseline erythrocyte fatty acid levels and scores on the Scale for the Assessment of Negative Symptoms (SANS) and Brief Psychiatric Rating Scale (BPRS).ResultsNegative symptoms were positively correlated with one saturated FA (Tetracosanoic acid [24:0], R=0.272, p<0.0001), one n-3 FA (Eicosapentaenoic acid [20:5], R=0.142, p=0.017) and one n-9 FA (Nervonic acid [24:1], R=0.274, p<0.0001), and negatively correlated with one saturated FA (Palmitic acid [16:0], R=-0.224, p<0.0001), two n-6 FAs (Dihomo-y-linolenc acid [20:3], R=-0.201, p<0.001 and Linolelaidic acid [18:2], R=-0.333, p<0.0001), and one n-7 FA (Vaccenic acid [18:1], R=-0.172, p=0.004). BPRS scores were positively correlated with one saturated FA (Tetracosanoic acid [24:0], R=0.363, p<0.0001) and one n-9 fatty acid (Nervonic acid [24:1], R=-0.346, p<0.0001), and negatively correlated with two n-3 FAs (Dihomo-y-linolenc acid [20:3], R=-0.153, p=0.010 and Docosahexaenoic acid [22:6], R=-0.193, p<0.001), and two n-6 FAs (Arachidonic acid [20:4], R=-0.125, p=0.037 and Linoleic acid [18:2], R=-0.340, p<0.0001).DiscussionConsistent with a previous study, negative symptoms and general psychopathology were associated with levels of several classes of FAs in the present study. These findings support the relevance of membrane fatty acids for the onset of psychotic symptoms and indicate that FAs should be further evaluated as biomarkers in people at UHR for psychosis.

O11.8. PREVALENCE AND PREDICTORS OF INTERVIEW-ASSESSED CLINICAL HIGH-RISK SYMPTOMS IN THE GENERAL POPULATION

BackgroundIn clinical samples, symptomatic ultra-high risk criteria and the basic symptom criterion “cognitive disturbances” perform well in predicting psychosis, and best when both approaches are combined. However, little-to-nothing is known about the prevalence, clinical relevance, and moderators of these clinical high risk (CHR) criteria and their constituent symptoms in the community.MethodsRegression analyses involved 2683 community participants (age 16–40 years; response rate: 63.4%). Semi-structured telephone interviews were performed by well-trained psychologists.ResultsLifetime and current CHR symptoms were reported by 21.1% and 13.8% of interviewees. Frequency of symptoms was mostly low, only 2.4% met any CHR criterion. A stepwise relationship underlay the association of the two types of CHR symptoms and criteria with the presence of mental disorders and functional deficits, with odds ratios being highest (7.4–31.8) when ultra-high risk and basic symptoms occurred together. Report of a family history of mental disorder generally increased risk for CHR symptoms. While younger age increased risk for basic symptoms, lifetime substance misuse and trauma increased risk for ultra-high risk symptoms.DiscussionPrevalence of CHR criteria was within the range to be expected from the prevalence rates of psychoses. Clinical relevance of both CHR symptoms and criteria increased in a stepwise manner from basic symptoms via ultra-high risk symptoms to their combined presence, reinforcing the clinical utility of their combined use. The risk factors selectively associated with basic and ultra-high risk symptoms seem to support developmental models relating basic symptoms to neurobiological and ultra-high risk symptoms to psychological factors.

Neighbourhood deprivation is positively associated with detection of the ultra-high risk (UHR) state for psychosis in South East London

BackgroundIndividuals are defined as being at ultra-high risk (UHR) for psychosis based on a combination of attenuated psychotic symptoms, help-seeking behaviour, genetic risk, and social/occupational deterioration. Limited evidence is available on whether UHR detection differs by neighbourhood, and potential explanations. AimsTo examine neighbourhood distribution of detected UHR using cases from the OASIS service in South East London, investigating neighbourhood deprivation as an explanatory variable. MethodsGeographic data were collected on patients who met UHR criteria over a fourteen-year period, at the neighbourhood (lower super output area, LSOA) level. Rates were calculated based on cases and age-specific population estimates. Poisson regression assessed associations between UHR rate and neighbourhood deprivation, and with particular deprivation domains, adjusting for referrals for UHR assessment, population density, and proportions of non-White people, and young single people. ResultsRate of UHR detection was statistically related to neighbourhood deprivation, but referral rate was not: compared to the least deprived neighbourhoods, the most deprived neighbourhoods had a greater than two-fold increase in incidence rate of detected UHR (adjusted incidence rate ratio (IRR): 2.11, 95% confidence interval (CI): 1.21,3.67). In contrast, a small, imprecise association was observed for referral for assessment for UHR (adjusted IRR: 1.26 (95%CI: 0.84,1.89)). Evidence was also found for associations of UHR detection rate with domains of deprivation pertaining to health and barriers to services. ConclusionsThe distribution of UHR detection rates by neighbourhood is not random and may be explained in part by differences in the social environment between neighbourhoods.

Psychotic conversion of individuals at ultra-high risk for psychosis: The potential roles of schizotypy and basic symptoms.

To improve strategies for the early identification of individuals at a heightened risk for the development of psychosis, we investigated the relationships and interactions between 3 psychosis-proneness dimensions for the development of schizophrenia spectrum psychosis: schizotypy, basic symptoms and the ultra-high risk (UHR) criteria. Seventy-seven UHR individuals and 79 healthy controls were assessed for schizotypy and basic symptoms using self-report questionnaires at baseline. UHR participants were monthly assessed for conversion to psychosis over a mean period of 25.8 months. Sixteen UHR participants (20.8%) converted to schizophrenia spectrum psychosis. In stepwise Cox regression, the interaction between basic symptoms and physical anhedonia was selected as a sole predictor of conversion in UHR participants, whereby the self-reported number of the 8 basic symptoms significantly increased the risk for conversion in those with pronounced physical anhedonia. Our findings suggest that questionnaire-assessed basic symptoms, irrespective of their predictive validity, may predict a psychotic breakdown in pre-identified UHR individuals who are with genetic vulnerability to schizophrenia. Including all 3 psychosis-proneness dimensions into prediction models might help establish a more valid pathogenetic model of schizophrenia, and moreover, may provide some clues about course alteration strategies in hopes of preventing UHR individuals from converting to psychosis.

Validation of the Korean version of the 16-Item Prodromal Questionnaire in a Non-Help-Seeking College Population.

Objective To examine the reliability and validity of the Korean version of the 16-item Prodromal Questionnaire (KPQ-16) in non-help-seeking university students. Methods Among 2,246 university students participated in the initial screening, 257 subjects with KPQ-16 scores ≥4 were interviewed. The criteria for ultra-high risk (UHR) of psychosis of the Comprehensive Assessment of At-Risk Mental States (CAARMS) were the gold standard for diagnosis. An exploratory modified version of the questionnaire (mKPQ-16), to which three items from the Eppendorf Schizophrenia Inventory were added, was also used to compensate for items on thought and cognitive problems. Results Seventeen subjects met the CAARMS criteria for UHR of psychosis. The area under the receiver operating characteristic curve (AUROC) was highest for the mKPQ-16 total score (AUROC=0.831, p<0.001). The use of cutoff total scores of 7 for the mKPQ-16 and 6 for the KPQ-16 resulted in the best balance of sensitivity (76.5% and 64.7%, respectively) and specificity (75.4% and 71.2%, respectively). Conclusion The Korean versions of the PQ-16 are good instruments for screening for psychosis risk in university students. This validation of a questionnaire version with a small number of items may make it feasible to screen large numbers of young adults in the community.

Dopamine in high-risk populations: A comparison of subjects with 22q11.2 deletion syndrome and subjects at ultra high-risk for psychosis

Striatal dopamine (DA) dysfunction has been consistently reported in psychotic disorders. Differences and similarities in the pathogenesis between populations at clinical and genetic risk for developing psychosis are yet to be established. Here we explored markers of dopamine (DA) function in subjects meeting clinically ultra-high risk criteria for psychosis (UHR) and in subjects with 22q11.2 deletion syndrome (22q11DS), a genetic condition associated with significant risk for developing psychotic disorders.Single Photon Emission Computed Tomography (SPECT) with 123I-labelled iodobenzamide ([123I]IBZM) was used to measure striatal DA D2/3 receptor binding potential (D2R BPND). Also, peripheral DAergic markers were assessed in serum and urine (plasma prolactin (pPRL), plasma homovanillic acid (pHVA) and urine DA(uDA)).No significant difference in striatal D2R BPND was found between UHR and 22q11DS subjects. Compared to UHR subjects, pPRL and pHVA were lower and uDA levels were higher in the 22q11DS subjects. However, after correcting for age and gender, only pPRL as significantly lower in the 22q11DS patients.These results may suggest that there are differences in DAergic markers between subjects with UHR and with 22q11DS that may reflect differences in the pathways to psychosis. However, bigger samples are needed to replicate these findings.

Adolescents at ultra-high risk of psychosis in Italian neuropsychiatry services: prevalence, psychopathology and transition rate.

Studies in adolescents on ultra-high risk (UHR) and basic symptoms (BS) criteria for psychosis prediction are scarce. In Italy, early interventions in psychosis are less widespread than in other European countries. In the present study, we (1) assessed the clinical relevance of a UHR diagnosis [according to the comprehensive assessment of at-risk mental states (CAARMS) criteria] to promote the implementation of specific services for UHR adolescents into the Italian health care system; (2) described severity of positive, negative, general, and basic symptoms in UHR adolescents compared to adolescents with first-episode psychosis (FEP) and non-UHR adolescents (i.e., individuals who did not meet CAARMS criteria for UHR or FEP); and (3) investigated the predictive validity of UHR criteria in relation to BS criteria. Seventy-nine adolescents (aged 13-18years) were assessed with the CAARMS, the positive and negative syndrome scale (PANSS), and the schizophrenia proneness instrument, child and youth version (SPI-CY). Both UHR (n=25) and FEP (n=11) had significantly higher PANSS subscale scores compared to non-UHR (n=43). UHR had significantly lower PANSS-positive symptom scores than FEP, but similar global functioning and PANSS-negative symptoms and general psychopathology scores. Compared to non-UHR, both FEP and UHR had more severe thought and perception BS disturbances, and significantly more often met BS criteria. After 12months, 2 of 20 (10%) UHR had transitioned to psychosis. They also met both BS criteria. Given the uncertain outcome of UHR adolescents, future research is needed to determine whether the combined assessment of BS with UHR symptoms can improve the accuracy of psychosis prediction in adolescence.

The Ultra-High-Risk for psychosis groups: Evidence to maintain the status quo

Individuals are considered Ultra-High-Risk (UHR) for psychosis if they meet a set of standardised criteria including presumed genetic vulnerability (Trait), or a recent history of Attenuated Psychotic Symptoms (APS) or Brief Limited Intermittent Psychotic Symptoms (BLIPS). Recent calls to revise these criteria have arisen from evidence that Trait, APS and BLIPS groups may transition to psychosis at different rates. Concurrently, it has become clear that the UHR status confers clinical risk beyond transition to psychosis. Specifically, most UHR individuals will not develop psychosis, but will experience high rates of non-psychotic disorders, persistent APS and poor long-term functional outcomes. Rather than focus on transition, the present study investigated whether UHR groups differ in their broader clinical risk profile by examining baseline clinical characteristics and long-term outcomes other than transition to psychosis. Four UHR groups were defined: Trait-only, APS-only, Trait+APS, and any BLIPS. Participants (N=702) were recruited upon entry to early intervention services and followed-up over a period of up to 13years (mean=4.53, SD=3.84). The groups evidenced similar symptom severity (SANS for negative symptoms, BPRS for positive and depression/anxiety symptoms) and psychosocial functioning (SOFAS, GAF, QLS) at baseline and follow-up as well as similar prevalence of non-psychotic disorders at follow-up. Our findings demonstrate that UHR groups evidence a similar clinical risk profile when we expand this beyond transition to psychosis, and consequently support maintaining the existing UHR criteria.

Broad clinical high-risk mental state (CHARMS): Methodology of a cohort study validating criteria for pluripotent risk.

The development of the ultra-high risk (UHR) criteria for psychosis created a new paradigm for the prevention research in psychiatry. Since (1) prevention research faces the challenge of achieving adequate statistical power when focusing on single low-incidence syndromes and (2) early clinical phenotypes are overlapping and non-specific, this study broadens the UHR state beyond psychosis as an outcome. The CHARMS (clinical high at-risk mental state) study aims to prospectively validate a set of trans-diagnostic criteria to identify help-seeking young people at risk of developing a range of serious mental illnesses. This paper describes the methodology of the CHARMS study, which involves applying the CHARMS criteria to a cohort of help-seeking young people aged 12 to 25 attending youth mental health services in Melbourne. New referrals meeting the CHARMS criteria are allocated to the CHARMS+ group; referrals not meeting CHARMS threshold are allocated to CHARMS- group (control group); referrals meeting criteria for a full-threshold disorder are excluded. Transition status and clinical and functional outcomes are re-assessed at 6 and 12 months. This study will be the first to introduce and validate clinical criteria to identify a broader at-risk patient population, which may facilitate young people's access to clinical services and early treatment by reducing the reliance on "caseness" defined according to current diagnostic categories being required for service entry. These criteria may introduce a new, trans-diagnostic approach for understanding risk factors and pathogenic mechanisms that drive the onset of severe mental illness and the next generation of preventive intervention trials.

Pre-onset risk characteristics for mania among young people at clinical high risk for psychosis

IntroductionPsychosis and mania share conceptual, genetic and clinical features, which suggest the possibility that they have common antecedents. Participants identified to be at-risk for psychosis might also be at-risk for mania. We aimed to identify the rate and predictors of transition to mania in a cohort of youth with clinical or familial risk for psychosis. MethodsAmong a cohort of 416 young people with an at-risk mental state for psychosis defined using the Ultra-High-Risk (UHR) criteria, 74.7% were followed up between 5 and 13years from their baseline assessment. We undertook a matched case-control examination of those who developed mania over the follow-up period compared to those who did not develop mania or psychosis. Transition to mania was determined using either a structured clinical interview, or diagnoses from a state-wide public mental health contact registry. Clinical characteristics and risk factors were examined at baseline using information from structured interviews, clinical file notes, rating scales and unstructured assessments. ResultsEighteen participants developed mania (UHR-Manic transition or UHR-M, 4.3%). In comparison with participants matched on age, gender and baseline-study who developed neither mania nor psychosis, more UHR-M participants had subthreshold manic symptoms or were prescribed antidepressants at baseline. They also had lower global functioning. DiscussionIn addition to the UHR criteria, features such as subthreshold manic symptoms and antidepressant use may help identify at-risk groups that predict the onset of mania in addition to transition to psychosis. Presence of manic symptoms may also indicate syndrome specificity early in the prodromal phase.

Why transition risk to psychosis is not declining at the OASIS ultra high risk service: The hidden role of stable pretest risk enrichment

BackgroundThe reason for declining risk to psychosis across individuals assessed and meeting Ultra High Risk (UHR) criteria is still unclear. No studies have investigated the potential substantial role of the underlying risk enrichment across all the individuals undergoing an UHR assessment. MethodsCohort study including all non-psychotic subjects who were assessed on suspicion of psychosis risk by the OASIS UHR service in the period 2001 to 2015. Posttest (after UHR assessment) and pretest risk (before UHR assessment) of psychosis were stratified and compared across three time periods (2001–2005, 2006–2010, 2011–2015) with Cox analysis and modulating factors were investigated. ResultsThe posttest risk of psychosis at the OASIS service has increased from the initial pilot years of the service (2001–2005) and then stabilised and not declined over the following decade (2006–2010 and 2011–2015). This was paralleled by a similar course of pretest risk for psychosis. Stability of pretest risk for psychosis over the past decade was associated with a lack of change in ethnicity and to counterweighting changes in the type of referral sources over different time periods. ConclusionsThe time course of transition risk to psychosis in UHR services is strictly associated with the time course of pretest risk enrichment. If the latter remains stable over time, as for the OASIS service, no declining transition risk is observed over the most recent years. Pretest risk enrichment is determined by recruitment and sampling strategies. This study confirms the need to control these factors in the UHR field.

Checking the predictive accuracy of basic symptoms against ultra high-risk criteria and testing of a multivariable prediction model: Evidence from a prospective three-year observational study of persons at clinical high-risk for psychosis

BackgroundThe aim of this study was to critically examine the prognostic validity of various clinical high-risk (CHR) criteria alone and in combination with additional clinical characteristics. MethodsA total of 188 CHR positive persons from the region of Zurich, Switzerland (mean age 20.5 years; 60.2% male), meeting ultra high-risk (UHR) and/or basic symptoms (BS) criteria, were followed over three years. The test battery included the Structured Interview for Prodromal Syndromes (SIPS), verbal IQ and many other screening tools. Conversion to psychosis was defined according to ICD-10 criteria for schizophrenia (F20) or brief psychotic disorder (F23). ResultsAltogether n=24 persons developed manifest psychosis within three years and according to Kaplan–Meier survival analysis, the projected conversion rate was 17.5%. The predictive accuracy of UHR was statistically significant but poor (area under the curve [AUC]=0.65, P<.05), whereas BS did not predict psychosis beyond mere chance (AUC=0.52, P=.730). Sensitivity and specificity were 0.83 and 0.47 for UHR, and 0.96 and 0.09 for BS. UHR plus BS achieved an AUC=0.66, with sensitivity and specificity of 0.75 and 0.56. In comparison, baseline antipsychotic medication yielded a predictive accuracy of AUC=0.62 (sensitivity=0.42; specificity=0.82). A multivariable prediction model comprising continuous measures of positive symptoms and verbal IQ achieved a substantially improved prognostic accuracy (AUC=0.85; sensitivity=0.86; specificity=0.85; positive predictive value=0.54; negative predictive value=0.97). ConclusionsWe showed that BS have no predictive accuracy beyond chance, while UHR criteria poorly predict conversion to psychosis. Combining BS with UHR criteria did not improve the predictive accuracy of UHR alone. In contrast, dimensional measures of both positive symptoms and verbal IQ showed excellent prognostic validity. A critical re-thinking of binary at-risk criteria is necessary in order to improve the prognosis of psychotic disorders.

Increased Striatal and Reduced Prefrontal Cerebral Blood Flow in Clinical High Risk for Psychosis.

Increased striatal dopaminergic activity and decreased prefrontal functioning have been reported in individuals at clinical high risk (CHR) for psychosis. Abnormal metabolic rate might affect resting-state cerebral blood flow (rCBF) in the respective regions. Here, we examined if striatal and prefrontal rCBF differ between patients with CHR, first-episode psychosis (FEP), chronic schizophrenia-spectrum disorder (SZ) and controls. Two cohorts with a total of 122 participants were included and analyzed separately: 32 patients with SZ and 31 healthy controls (HC) from the University Hospital of Psychiatry, and 59 patients from the Bern Early Recognition and Intervention Center (29 with CHR, 12 with FEP, and 18 clinical controls [CC]). Ultra-high risk criteria were assessed with the Structured Interview for Psychosis-Risk Syndromes, basic symptom criteria with the Schizophrenia Proneness Instrument. rCBF was measured with pseudo-continuous arterial spin labeling 3T-Magnetic Resonance Imaging. Striatal rCBF was significantly increased and prefrontal rCBF significantly decreased in the SZ group compared to HC group and in the CHR and FEP groups compared to CC group. Striatal rCBF correlated significantly with positive symptom scores in SZ and CHR. An inverse correlation between striatal and frontal rCBF was found in controls (HC, CC), but not in patient groups (SZ, FEP, CHR). This is the first study to demonstrate increased neuronal activity within the striatum, but reduced prefrontal activity in patients with CHR, FEP, and SZ compared to the respective controls. Our results indicate that alterations in striatal and prefrontal rCBF are reflecting metabolic abnormalities preceding the onset of frank psychosis.

Developmental Aspects in the Early Detection and Intervention in Clinical High Risk States for Psychosis

Developmental Aspects in the Early Detection and Intervention in Clinical High Risk States for Psychosis The early detection and intervention in psychoses, which are a main source of disability-adjusted life years already in children and adolescents, have made good progress within the past years. In particular the attenuated and transient positive symptoms of the ultra-high risk criteria and the basic symptom criterion "Cognitive Disturbances" open promising routes to an indicated prevention and have recently been considered as diagnostic criteria of a psychosis-risk syndrome by the European Psychiatric Association (EPA). However, because their association with a development of psychosis has been weaker in children and adolescents than in adults, only the assessment and monitoring of these risk symptoms was recommended for children and adolescents, while interventions aiming at the prevention of psychoses were discouraged. Furthermore, treatment of comorbid current mental disorders and psychosocial problems over the prevention of a potential future disorder also characterizes the intervention recommendations of the EPA. Furthermore, these give primacy to psychological, in particular cognitive-behavioral interventions over psychopharmacological treatments. Yet, also with regard to an early intervention, current evidence indicates that children and adolescents might benefit less than adults. Overall, age-related or developmental peculiarities in the early detection and intervention in psychoses become more and more apparent and should be more focused in future research in this field.

Treatment of people at ultra-high risk for psychosis.

Treatment of people at ultra-high risk for psychosis.

The effect of cognitive remediation in individuals at ultra-high risk for psychosis: a systematic review

Cognitive deficits are prominent features of the ultra-high risk state for psychosis that are known to impact functioning and course of illness. Cognitive remediation appears to be the most promising treatment approach to alleviate the cognitive deficits, which may translate into functional improvements. This study systematically reviewed the evidence on the effectiveness of cognitive remediation in the ultra-high risk population. The electronic databases MEDLINE, PsycINFO, and Embase were searched using keywords related to cognitive remediation and the UHR state. Studies were included if they were peer-reviewed, written in English, and included a population meeting standardized ultra-high risk criteria. Six original research articles were identified. All the studies provided computerized, bottom-up-based cognitive remediation, predominantly targeting neurocognitive function. Four out of five studies that reported a cognitive outcome found cognitive remediation to improve cognition in the domains of verbal memory, attention, and processing speed. Two out of four studies that reported on functional outcome found cognitive remediation to improve the functional outcome in the domains of social functioning and social adjustment. Zero out of the five studies that reported such an outcome found cognitive remediation to affect the magnitude of clinical symptoms. Research on the effect of cognitive remediation in the ultra-high risk state is still scarce. The current state of evidence indicates an effect of cognitive remediation on cognition and functioning in ultra-high risk individuals. More research on cognitive remediation in ultra-high risk is needed, notably in large-scale trials assessing the effect of neurocognitive and/or social cognitive remediation on multiple outcomes.

Impairment in Social Functioning differentiates youth meeting Ultra-High Risk for psychosis criteria from other mental health help-seekers: A validation of the Italian version of the Global Functioning: Social and Global Functioning: Role scales

Social and occupational impairments are present in the schizophrenia prodrome, and poor social functioning predicts transition to psychosis in Ultra-High Risk (UHR) individuals. We aimed to: 1) validate the Italian version of the Global Functioning: Social (GF: S) and Global Functioning: Role (GF: S) scales; 2) evaluate their association with UHR criteria. Participants were 12–21-years-old (age, mean=15.2, standard deviation=2.1, male/female ratio=117/120) nonpsychotic help-seekers, meeting (N=39) or not (N=198) UHR criteria. Inter-rater reliability was excellent for both scales, which also showed good to excellent concurrent validity, as measured by correlation with Global Assessment of Functioning (GAF) scores. Furthermore, GF:S and GF: R were able to discriminate between UHRs and non-UHRs, with UHRs having lower current scores. After adjusting for current GAF scores, only current GF:S scores independently differentiated UHR from non-UHR (OR=1.33, 95%CI: 1.02–1.75, p=0.033). Finally, UHR participants showed a steeper decrease from highest GF:S and GF: R scores in the past year to their respective current scores, but not from highest past year GAF scores to current scores. GF:S/GS: R scores were not affected by age or sex. GF:S/GF: R are useful functional level and outcome measures, having the advantage over the GAF to not confound functioning with symptom severity. Additionally, the GF:S may be helpful in identifying UHR individuals.