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AIM: Basic self disturbance is a putative core vulnerability marker of schizophrenia spectrum disorders. The primary aims of the Self, Neuroscience and Psychosis (SNAP) study are to: (1) empirically test a previously described neurophenomenological self-disturbance model of psychosis by examining the relationship between specific clinical, neurocognitive, and neurophysiological variables in UHR patients, and (2) develop a prediction model using these neurophenomenological disturbances for persistence or deterioration of UHR symptoms at 12-month follow-up. METHODS: SNAP is a longitudinal observational study. Participants include 400 UHR individuals, 100 clinical controls with no attenuated psychotic symptoms, and 50 healthy controls. All participants complete baseline clinical and neurocognitive assessments and electroencephalography. The UHR sample are followed up for a total of 24 months, with clinical assessment completed every 6 months. RESULTS: This paper presents the protocol of the SNAP study, including background rationale, aims and hypotheses, design, and assessment procedures. CONCLUSIONS: The SNAP study will test whether neurophenomenological disturbances associated with basic self-disturbance predict persistence or intensification of UHR symptomatology over a 2-year follow up period, and how specific these disturbances are to a clinical population with attenuated psychotic symptoms. This may ultimately inform clinical care and pathoaetiological models of psychosis.

AIM: To harmonize two ascertainment and severity rating instruments commonly used for the clinical high risk syndrome for psychosis (CHR-P): the Structured Interview for Psychosis-risk Syndromes (SIPS) and the Comprehensive Assessment of At-Risk Mental States (CAARMS). METHODS: The initial workshop is described in the companion report from Addington et al. After the workshop, lead experts for each instrument continued harmonizing attenuated positive symptoms and criteria for psychosis and CHR-P through an intensive series of joint videoconferences. RESULTS: Full harmonization was achieved for attenuated positive symptom ratings and psychosis criteria, and modest harmonization for CHR-P criteria. The semi-structured interview, named Positive SYmptoms and Diagnostic Criteria for the CAARMS Harmonized with the SIPS (PSYCHS), generates CHR-P criteria and severity scores for both CAARMS and SIPS. CONCLUSIONS: Using the PSYCHS for CHR-P ascertainment, conversion determination, and attenuated positive symptom severity rating will help in comparing findings across studies and in meta-analyses.

This article describes the rationale, aims, and methodology of the Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ). This is the largest international collaboration to date that will develop algorithms to predict trajectories and outcomes of individuals at clinical high risk (CHR) for psychosis and to advance the development and use of novel pharmacological interventions for CHR individuals. We present a description of the participating research networks and the data processing analysis and coordination center, their processes for data harmonization across 43 sites from 13 participating countries (recruitment across North America, Australia, Europe, Asia, and South America), data flow and quality assessment processes, data analyses, and the transfer of data to the National Institute of Mental Health (NIMH) Data Archive (NDA) for use by the research community. In an expected sample of approximately 2000 CHR individuals and 640 matched healthy controls, AMP SCZ will collect clinical, environmental, and cognitive data along with multimodal biomarkers, including neuroimaging, electrophysiology, fluid biospecimens, speech and facial expression samples, novel measures derived from digital health technologies including smartphone-based daily surveys, and passive sensing as well as actigraphy. The study will investigate a range of clinical outcomes over a 2-year period, including transition to psychosis, remission or persistence of CHR status, attenuated positive symptoms, persistent negative symptoms, mood and anxiety symptoms, and psychosocial functioning. The global reach of AMP SCZ and its harmonized innovative methods promise to catalyze the development of new treatments to address critical unmet clinical and public health needs in CHR individuals.

OBJECTIVE: To develop targeted treatment for young people experiencing mental illness, a better understanding of the biological, psychological, and social changes is required, particularly during the early stages of illness. To do this, large datasets need to be collected using standardized methods. A harmonized data collection protocol was tested in a youth mental health research setting to determine its acceptability and feasibility. METHOD: Eighteen participants completed the harmonization protocol, including a clinical interview, self-report measures, neurocognitive measures, and mock assessments of magnetic resonance imaging (MRI) and blood. The feasibility of the protocol was assessed by recording recruitment rates, study withdrawals, missing data, and protocol deviations. Subjective responses from participant surveys and focus groups were used to examine the acceptability of the protocol. RESULTS: Twenty-eight young people were approached, 18 consented, and four did not complete the study. Most participants reported positive subjective impressions of the protocol as a whole and showed interest in participating in the study again, if given the opportunity. Participants generally perceived the MRI and neurocognitive tasks as interesting and suggested that the assessment of clinical presentation could be shortened. CONCLUSION: Overall, the harmonized data collection protocol appeared to be feasible and generally well-accepted by participants. With a majority of participants finding the assessment of clinical presentation too long and repetitive, the authors have made suggestions to shorten the self-reports. The broader implementation of this protocol could allow researchers to create large datasets and better understand how psychopathological and neurobiological changes occur in young people with mental ill-health.

Cette boîte à outils explore les enjeux politiques et techniques à considérer lors de la planification d'une serre communautaire urbaine. Vous y trouverez les faits saillants, des fiches techniques sur l'efficacité énergétique des enveloppes de serre, sur le potentiel de la géothermie, sur la gestion des eaux de pluie et lessivées et un calculateur de GES. Vous trouverez également des études de cas des serres communautaires des Jardins Gamelin, du Bâtiment 7, de Santropol Roulant, des Jardins des Patriotes et Emily-de-Witt, puis une exploration des enjeux de gentrification verte, de financement, de partenariats et d'inclusion à l'égard des multiples missions que peuvent remplir les serres.

Understanding longitudinal cognitive performance in individuals at ultra-high risk for psychosis (UHR) is important for informing theoretical models and treatment. A vital step in this endeavor is to determine whether there are UHR subgroups that have similar patterns of cognitive change over time. The aims were to: i) identify latent class trajectories of cognitive performance over 12-months in UHR individuals, ii) identify baseline demographic and clinical predictors of the resulting classes, and iii) determine whether trajectory classes were associated with transition to psychosis or functional outcomes. Cognition was assessed using the Brief Assessment of Cognition in Schizophrenia (BACS) at baseline, 6- and 12-months (N = 288). Using Growth Mixture Modeling, a single unimpaired improving trajectory class was observed for motor function, speed of processing, verbal fluency, and BACS composite. A two-class solution was observed for executive function and working memory, showing one unimpaired and a second impaired class. A three-class solution was found for verbal learning and memory: unimpaired, mildly impaired, and initially extremely impaired, but improved ("caught up") to the level of the mildly impaired. IQ, omega-3 index, and premorbid adjustment were associated with class membership, whereas clinical variables (symptoms, substance use), including transition to psychosis, were not. Working memory and verbal learning and memory trajectory class membership was associated with functioning outcomes. These findings suggest there is no short-term progressive cognitive decline in help-seeking UHR individuals, including those who transition to psychosis. Screening of cognitive performance may be useful for identifying UHR individuals who may benefit from targeted cognitive interventions.

Purpose: Migrant status is one of the most replicated and robust risk factors for developing a psychotic disorder. This study aimed to determine whether migrant status in people identified as Ultra-High Risk for Psychosis (UHR) was associated with risk of transitioning to a full-threshold psychotic disorder. Methods: Hazard ratios for the risk of transition were calculated from five large UHR cohorts (n = 2166) and were used to conduct a meta-analysis using the generic inverse-variance method using a random-effects model. Results: 2166 UHR young people, with a mean age of 19.1 years (SD ± 4.5) were included, of whom 221 (10.7%) were first-generation migrants. A total of 357 young people transitioned to psychosis over a median follow-up time of 417 days (I.Q.R.147–756 days), representing 17.0% of the cohort. The risk of transition to a full-threshold disorder was not increased for first-generation migrants, (HR = 1.08, 95% CI 0.62–1.89); however, there was a high level of heterogeneity between studies The hazard ratio for second-generation migrants to transition to a full-threshold psychotic disorder compared to the remainder of the native-born population was 1.03 (95% CI 0.70–1.51). Conclusions: This meta-analysis did not find a statistically significant association between migrant status and an increased risk for transition to a full-threshold psychotic disorder; however, several methodological issues could explain this finding. Further research should focus on examining the risk of specific migrant groups and also ensuring that migrant populations are adequately represented within UHR clinics.

PURPOSE: Migrant status is one of the most replicated and robust risk factors for developing a psychotic disorder. This study aimed to determine whether migrant status in people identified as Ultra-High Risk for Psychosis (UHR) was associated with risk of transitioning to a full-threshold psychotic disorder. METHODS: Hazard ratios for the risk of transition were calculated from five large UHR cohorts (n = 2166) and were used to conduct a meta-analysis using the generic inverse-variance method using a random-effects model. RESULTS: 2166 UHR young people, with a mean age of 19.1 years (SD ± 4.5) were included, of whom 221 (10.7%) were first-generation migrants. A total of 357 young people transitioned to psychosis over a median follow-up time of 417 days (I.Q.R.147-756 days), representing 17.0% of the cohort. The risk of transition to a full-threshold disorder was not increased for first-generation migrants, (HR = 1.08, 95% CI 0.62-1.89); however, there was a high level of heterogeneity between studies The hazard ratio for second-generation migrants to transition to a full-threshold psychotic disorder compared to the remainder of the native-born population was 1.03 (95% CI 0.70-1.51). CONCLUSIONS: This meta-analysis did not find a statistically significant association between migrant status and an increased risk for transition to a full-threshold psychotic disorder; however, several methodological issues could explain this finding. Further research should focus on examining the risk of specific migrant groups and also ensuring that migrant populations are adequately represented within UHR clinics.

AIM: Investigating biological processes in at-risk individuals may help elucidate the aetiological mechanisms underlying psychosis development, refine prediction models and improve intervention strategies. This study examined the associations between sleep disturbances, chronotype, depressive and psychotic symptoms in individuals at ultra-high risk for psychosis. METHODS: A sample of 81 ultra-high risk patients completed clinical interviews and self-report assessments of chronotype and sleep during the Neurapro clinical trial. Mixed regression was used to investigate the cross-sectional associations between symptoms and sleep disturbances/chronotype. RESULTS: Sleep disturbances were significantly associated with increased depressive and attenuated positive psychotic symptoms. Greater preference for eveningness was significantly associated with increased negative symptoms, but not with depressive or attenuated positive psychotic symptoms. CONCLUSION: Sleep disturbances and chronotype may impact the emerging psychopathology experienced by ultra-high risk individuals. Further, the preliminary relationship observed between greater preference for eveningness and negative symptoms offers a unique opportunity to treat negative symptoms through chronobiological approaches.

AIM: Several prediction models have been introduced to identify young people at greatest risk of transitioning to psychosis. To date, none has examined the possibility of developing a clinical prediction model of outcomes other than transition. The aims of this study were to examine the association between baseline clinical predictors and outcomes including, but not limited to, transition to psychosis in young people at risk for psychosis, and to develop a prediction model for these outcomes. METHODS: Several evidence-based variables previously associated with transition to psychosis and some important clinical comorbidities experienced by ultra-high risk (UHR) individuals were identified in 202 UHR individuals. Secondary analysis of the Neurapro clinical trial were conducted to investigate the associations between these variables and favourable (remission and recovery) or unfavourable (transition to psychosis, no remission, any recurrence and relapse) clinical outcomes. Logistic regression, best subset selection, Akaike Information Criterion and receiver operating characteristic curves were used to seek the best prediction model for clinical outcomes from all combinations of possible predictors. RESULTS: When considered individually, only higher general psychopathology levels (P = .023) was associated with the unfavourable outcomes. Prediction models suggest that general psychopathology and functioning are predictive of unfavourable outcomes. CONCLUSION: The predictive performance of the resulting models was modest and further research is needed. Nonetheless, when designing early intervention centres aiming to support individuals in the early phases of a mental disorder, the proper assessment of general psychopathology and functioning should be considered in order to inform interventions and length of care provided.

BACKGROUND: The integration of various domains or levels of analysis (clinical, neurobiological, genetic, etc.) has been a challenge in schizophrenia research. A promising approach is to use the core phenomenological features of the disorder as an organising principle for other levels of analysis. Minimal self-disturbance (fragility in implicit first-person perspective, presence and agency) is emerging as a strong candidate to play this role. This approach was adopted in a previously described theoretical neurophenomenological model that proposed that source monitoring deficits and aberrant salience may be neurocognitive/neurobiological processes that correlate with minimal self-disturbance on the phenomenological level, together playing an aetiological role in the onset of schizophrenia spectrum disorders. The current paper presents full cross-sectional data from the first empirical test of this model.METHODS: Fifty ultra-high risk for psychosis patients, 39 first episode psychosis patients and 34 healthy controls were assessed with a variety of clinical measures, including the Examination of Anomalous Self-Experience (EASE), and neurocognitive and neurophysiological (EEG) measures of source monitoring deficits and aberrant salience.RESULTS: Linear regression indicated that source monitoring (composite score across neurocognitive and neurophysiological measures), with study group as an interaction term, explained 39.8% of the variance in EASE scores (R2 = 0.41, F(3,85) = 14.78, p < 0.001), whereas aberrant salience (composite score) explained only 6% of the variance in EASE scores (R2 = 0.06, F(3,85) = 1.44, p = 0.93). Aberrant salience measures were more strongly related to general psychopathology measures, particularly to positive psychotic symptoms, than to EASE scores.DISCUSSION: A neurophenomenological model of minimal self-disturbance in schizophrenia spectrum disorders may need to be expanded from source monitoring deficits to enco

Background: The integration of various domains or levels of analysis (clinical, neurobiological, genetic, etc.) has been a challenge in schizophrenia research. A promising approach is to use the core phenomenological features of the disorder as an organising principle for other levels of analysis. Minimal self-disturbance (fragility in implicit first-person perspective, presence and agency) is emerging as a strong candidate to play this role. This approach was adopted in a previously described theoretical neurophenomenological model that proposed that source monitoring deficits and aberrant salience may be neurocognitive/neurobiological processes that correlate with minimal self-disturbance on the phenomenological level, together playing an aetiological role in the onset of schizophrenia spectrum disorders. The current paper presents full cross-sectional data from the first empirical test of this model. Methods: Fifty ultra-high risk for psychosis patients, 39 first episode psychosis patients and 34 healthy controls were assessed with a variety of clinical measures, including the Examination of Anomalous Self-Experience (EASE), and neurocognitive and neurophysiological (EEG) measures of source monitoring deficits and aberrant salience. Results: Linear regression indicated that source monitoring (composite score across neurocognitive and neurophysiological measures), with study group as an interaction term, explained 39.8% of the variance in EASE scores (R2 = 0.41, F(3,85) = 14.78, p < 0.001), whereas aberrant salience (composite score) explained only 6% of the variance in EASE scores (R2 = 0.06, F (3,85) = 1.44, p = 0.93). Aberrant salience measures were more strongly related to general psychopathology measures, particularly to positive psychotic symptoms, than to EASE scores. Discussion: A neurophenomenological model of minimal self-disturbance in schizophrenia spectrum disorders may need to be expanded from source monitoring deficits to encompass other relevant co

This study examined whether distress in relation to attenuated psychotic symptoms (DAPS) is associated with clinical outcomes in an ultra-high-risk (UHR) for psychosis sample. We also investigated whether DAPS is associated with cognitive style (attributional style and cognitive biases) and whether amount of psychosocial treatment provided is associated with reduction in DAPS. The study was a secondary analysis of the 'Neurapro' clinical trial of omega-3 fatty acids. 304 UHR patients were recruited across ten early intervention services. Data from baseline assessment, regular assessments over 12 months and medium term follow up (mean=3.4 years) were used for analysis. Findings indicated: a positive association between DAPS assessed over time and transition to psychosis; a significant positive association between baseline and longitudinal DAPS and transdiagnostic clinical and functional outcomes; a significant positive association between baseline and longitudinal DAPS and non-remission of UHR status. There was no relationship between severity of DAPS and cognitive style. A greater amount of psychosocial treatment (cognitive-behavioural case management) was associated with an increase in DAPS scores. The study indicates that UHR patients who are more distressed by their attenuated psychotic symptoms are more likely to have a poorer clinical trajectory transdiagnostically. Assessment of DAPS may therefore function as a useful marker of risk for a range of poor outcomes. The findings underline the value of repeated assessment of variables and incorporation of dynamic change into predictive modelling. More research is required into mechanisms driving distress associated with symptoms and the possible bidirectional relationship between symptom severity and associated distress.

There has been limited research into the predictive value of basic symptoms and their relationship with other psychopathology in patients identified using the 'ultra high risk' (UHR) for psychosis approach. The current study investigated whether basic symptoms, specifically cognitive disturbances (COGDIS), were associated with a greater risk of transition to psychotic disorder and persistent attenuated psychotic symptoms (APS) at medium term follow-up (mean = 3.4 years) in UHR patients, as well as with general psychopathology at baseline. The sample included 304 UHR participants (mean age = 19.12 years) involved in an international multicenter trial of omega-3 fatty acids. UHR individuals who also met the COGDIS criteria (basic symptoms risk criteria) did not have a greater risk of transition than those who met the UHR criteria alone. However, meeting COGDIS risk criteria was associated with a greater likelihood of meeting the UHR attenuated psychotic symptoms risk group (i.e., having persistent attenuated psychotic symptoms) at 12-month follow-up (odds ratio = 1.85; 95% CI = 1.03, 3.32). Greater severity of cognitive basic symptoms was also independently associated with more severe general psychopathology at study entry. The findings do not support the notion that combined risk identification approaches (UHR and basic symptoms) aid in the identification of individuals at greatest risk of psychosis, although this interpretation is limited by the modest transition to psychosis rate (13%) and the time of follow up. However, the findings indicate that basic symptoms may be a clinically useful marker of more severe general psychopathology in UHR groups and risk for persistent attenuated psychotic symptoms.

The Ultra-High Risk (UHR) for psychosis group is known to be heterogeneous with diverse outcomes. This study aimed to: 1. Identify subclasses of UHR individuals based on trajectories of symptomatic and functional change over time, 2. Identify predictors of these trajectories. A sample of 304 UHR individuals participating in the Neurapro trial were followed over an average of 40 months. All participants received cognitive-behavioural case management (CBCM). Symptomatic and functional profiles were investigated using latent class growth analysis. Multinomial regression was employed to investigate predictors of classes. Identified trajectories showed mostly parallel slopes (i.e. improving symptoms/functioning over time), which were primarily distinct regarding the severity of symptomatology/level of functioning at baseline (i.e. the intercept). Higher symptomatic/lower functioning classes were predicted by higher substance use, older age, female gender, and lower cognitive functioning. No divergent trajectories were identified as all classes improved over time. This may reflect effective treatment through CBCM, natural illness course, or effective engagement with mental health services. Nonetheless, classes highest in symptoms/lowest in functioning still showed considerable impairment during follow-up, highlighting the need for targeted intervention in these subgroups. The study emphasizes the need for more clinical attention directed towards UHR patients being female or using substances.

OBJECTIVE: The current international trend is to create large datasets with existing data and/or deposit newly collected data into repositories accessible to the scientific community. These practices lead to more efficient data sharing, better detection of small effects, modelling of confounders, establishment of sample generalizability and identification of differences between any given disorders. In Australia, to facilitate such data-sharing and collaborative opportunities, the Neurobiology in Youth Mental Health Partnership was created. This initiative brings together specialised researchers from around Australia to work towards a better understanding of the cross-diagnostic neurobiology of youth mental health and the translation of this knowledge into clinical practice. One of the mandates of the partnership was to develop a protocol for harmonised prospective collection of data across research centres in the field of youth mental health in order to create large datasets. METHODS: Four key research modalities were identified: clinical assessments, brain imaging, neurocognitive assessment and collection of blood samples. This paper presents the consensus set of assessments/data collection that has been selected by experts in each domain. CONCLUSION: The use of this core set of data will facilitate the pooling of psychopathological and neurobiological data into large datasets allowing researchers to tackle important questions requiring very large numbers. The aspiration of this transdiagnostic approach is a better understanding of the mechanisms underlying mental illnesses.

BACKGROUND AND AIMS: The notion of basic self-disturbance has been proposed as a core feature of schizophrenia-spectrum disorders and as an indicator of future transition to psychosis in high-risk populations. However, the relation of this notion to many clinical characteristics has not been explored. The aim of this study was: (a) to investigate the distribution of self-disturbance and other symptoms dimensions in ultra-high risk (UHR), first-episode psychosis (FEP) and healthy control groups; and (b) to explore the association of self-disturbance with a history of self-harm, suicidal attempt, eating disorder symptomatology, school bullying victimization and sexual or physical abuse. METHODS: Patients with UHR status (n = 38) or FEP (n = 26) and healthy controls (n = 33) were assessed with the Examination of Anomalous Self-Experience (EASE) and the Comprehensive Assessment of at Risk Mental States (CAARMS). The clinical-historical variables were assessed through medical records. RESULTS: The FEP group scored significantly higher on the EASE than the UHR group, which scored significantly higher than the healthy control group, which had a very low score. Multivariate logistic regression analyses revealed that higher EASE score was significantly associated with a history of self-harm, disordered eating and bullying victimization (but not with suicide attempts or sexual/physical abuse) after controlling for positive, negative and depressive symptoms. CONCLUSION: These novel findings suggest that self-disturbance may be related to a history of school bullying victimization, self-harm and eating disorder symptomatology in patients with or at-risk of psychosis. If further confirmed, these findings are potentially relevant to clinical risk assessment and therapy.

There has been limited research into the predictive value of basic symptoms and their relationship with other psychopathology in patients identified using the ‘ultra high risk’ (UHR) for psychosis approach. The current study investigated whether basic symptoms, specifically cognitive disturbances (COGDIS), were associated with a greater risk of transition to psychotic disorder and persistent attenuated psychotic symptoms (APS) at medium term follow-up (mean = 3.4 years) in UHR patients, as well as with general psychopathology at baseline. The sample included 304 UHR participants (mean age = 19.12 years) involved in an international multicenter trial of omega-3 fatty acids. UHR individuals who also met the COGDIS criteria (basic symptoms risk criteria) did not have a greater risk of transition than those who met the UHR criteria alone. However, meeting COGDIS risk criteria was associated with a greater likelihood of meeting the UHR attenuated psychotic symptoms risk group (i.e., having persistent attenuated psychotic symptoms) at 12-month follow-up (odds ratio = 1.85; 95% CI = 1.03, 3.32). Greater severity of cognitive basic symptoms was also independently associated with more severe general psychopathology at study entry. The findings do not support the notion that combined risk identification approaches (UHR and basic symptoms) aid in the identification of individuals at greatest risk of psychosis, although this interpretation is limited by the modest transition to psychosis rate (13%) and the time of follow up. However, the findings indicate that basic symptoms may be a clinically useful marker of more severe general psychopathology in UHR groups and risk for persistent attenuated psychotic symptoms.

AIM: The Inventory of Psychotic-Like Anomalous Self-Experiences (IPASE) is a self-report measure of minimal self-disturbance. The aim of the current report was to assess the construct validity of the scale by examining its convergent validity with the gold-standard measure of minimal self-disturbance, the Examination of Anomalous Self-Experience (EASE), and its discriminant validity. METHOD: The sample consisted of 46 participants (21 ultra-high risk for psychosis patients, 14 first episode psychosis patients, 11 healthy controls). Correlations between the clinical instruments were examined. RESULTS: The IPASE correlated strongly with general psychopathology and positive psychotic symptoms, moderately with negative symptoms, and weakly with manic symptoms. The strongest correlation (r = 0.92) was apparent between IPASE and EASE total scores. CONCLUSION: These preliminary data indicate construct validity of the IPASE, demonstrating both convergent and discriminant validity. The IPASE may be suitable as a screener measure for minimal self-disturbance, but should not be used as a replacement to measure the construct of minimal self-disturbance, which requires considerable psychopathological sophistication.

AIM: Clinical staging in psychiatry aims to classify patients according to the severity of their symptoms, from stage 0 (increased risk, asymptomatic) to stage 4 (severe illness), enabling adapted treatment at each stage of the illness. The staging model would gain specificity if one or more quantifiable biological markers could be identified. Several biomarkers reflecting possible causal mechanisms and/or consequences of the pathophysiology are candidates for integration into the clinical staging model of psychiatric illnesses. METHODS: This review covers the evolution (from stage 0 to stage 4) of the most important brain functioning impairments as measured with electroencephalography (EEG), in psychosis spectrum and in severe mood disorders. RESULTS: The present review of the literature demonstrates that it is currently not possible to draw any conclusion with regard to the state or trait character of any of the EEG impairments in both major depressive disorder and bipolar disorder. As for schizophrenia, the most promising markers of the stage of the illness are the pitch mismatch negativity as well as the p300 event-related potentials, as these components seem to deteriorate with increasing severity of the illness. CONCLUSIONS: Given the complexity of major psychiatric disorders, and that not a single impairment can be observed in all patients, future research should most likely consider combinations of markers in the quest for a better identification of the stages of the psychiatric illnesses.

The XXL survey currently covers two 25 deg(2) patches with XMM observations of similar to 10 ks. We summarize the scientific results associated with the first release of the XXL dataset, which occurred in mid-2016. We review several arguments for increasing the survey depth to 40 ks during the next decade of XMM operations. X-ray (z < 2) cluster, (z < 4) active galactic nuclei (AGN), and cosmic background survey science will then benefit from an extraordinary data reservoir. This, combined with deep multi-lambda observations, will lead to solid standalone cosmological constraints and provide a wealth of information on the formation and evolution of AGN, clusters, and the X-ray background. In particular, it will offer a unique opportunity to pinpoint the z > 1 cluster density. It will eventually constitute a reference study and an ideal calibration field for the upcoming eROSITA and Euclid missions.

A high proportion of individuals deemed at elevated risk for psychosis will actually never progress to develop the illness. Pharmaceutical intervention may not be necessary in these cases, and may in fact be damaging depending on the invasiveness of the treatment strategy. This highlights the need for biomarkers that are better able to reliably differentiate between at-risk individuals who will subsequently transition to psychosis and those who will not. Low glutathione (GSH) levels have been observed in schizophrenia and in patients with first-episode psychosis. The aim of this study was to determine the predictive value of erythrocyte GSH levels on the transition to psychosis in individuals at risk of developing the illness. Erythrocyte GSH levels were measured in 36 at-risk individuals, 15 of whom had transitioned to psychosis at the 7-year follow-up. Univariate Cox regression analysis showed that transition to psychosis at the 7-year time point was significantly associated with low GSH levels at baseline. The area under the receiving operating characteristic curve was 0.819, indicating that GSH can be considered a good predictor of outcome. Although these results need to be replicated, adding the criterion 'low erythrocyte GSH' to the set of criteria used to identify individuals at risk of psychosis may be indicated.

Current criteria identifying patients with ultra-high risk of psychosis (UHR) have low specificity, and less than one-third of UHR cases experience transition to psychosis within 3 years of initial assessment. We explored whether a Bayesian probabilistic multimodal model, combining baseline historical and clinical risk factors with biomarkers (oxidative stress, cell membrane fatty acids, resting quantitative electroencephalography (qEEG)), could improve this specificity. We analyzed data of a UHR cohort (n=40) with a 1-year transition rate of 28%. Positive and negative likelihood ratios were calculated for predictor variables with statistically significant receiver operating characteristic curves (ROCs), which excluded oxidative stress markers and qEEG parameters as significant predictors of transition. We clustered significant variables into historical (history of drug use), clinical (Positive and Negative Symptoms Scale positive, negative and general scores and Global Assessment of Function) and biomarker (total omega-3, nervonic acid) groups, and calculated the post-test probability of transition for each group and for group combinations using the odds ratio form of Bayes' rule. Combination of the three variable groups vastly improved the specificity of prediction (area under ROC=0.919, sensitivity=72.73%, specificity=96.43%). In this sample, our model identified over 70% of UHR patients who transitioned within 1 year, compared with 28% identified by standard UHR criteria. The model classified 77% of cases as very high or low risk (P>0.9, <0.1) based on history and clinical assessment, suggesting that a staged approach could be most efficient, reserving fatty-acid markers for 23% of cases remaining at intermediate probability following bedside interview.

Glutathione (GSH) deficits have been observed in several mental or degenerative illness, and so has the metabolic syndrome. The impact of a decreased glucose metabolism on the GSH system is well-known, but the effect of decreased GSH levels on the energy metabolism is unclear. The aim of the present study was to investigate the sensitivity to insulin in the mouse knockout (KO) for the modulatory subunit of the glutamate cysteine ligase (GCLM), the rate-limiting enzyme of GSH synthesis. Compared to wildtype (WT) mice, GCLM-KO mice presented with reduced basal plasma glucose and insulin levels. During an insulin tolerance test, GCLM-KO mice showed a normal fall in glycemia, indicating normal insulin secretion. However, during the recovery phase, plasma glucose levels remained lower for longer in KO mice despite normal plasma glucagon levels. This is consistent with a normal counterregulatory hormonal response but impaired mobilization of glucose from endogenous stores. Following a resident-intruder stress, during which stress hormones mobilize glucose from hepatic glycogen stores, KO mice showed a lower hyperglycemic level despite higher plasma cortisol levels when compared to WT mice. The lower hepatic glycogen levels observed in GCLM-KO mice could explain the impaired glycogen mobilization following induced hypoglycemia. Altogether, our results indicate that reduced liver glycogen availability, as observed in GCLM-KO mice, could be at the origin of their lower basal and challenged glycemia. Further studies will be necessary to understand how a GSH deficit, typically observed in GCLM-KO mice, leads to a deficit in liver glycogen storage.