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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.

BackgroundMalhi et al. in this issue critique the clinical high risk (CHR) syndrome for psychosis.MethodResponse to points of critique.ResultsWe agree that inconsistency in CHR nomenclature should be minimized. We respectfully disagree on other points. In our view: a) individuals with CHR and their families need help, using existing interventions, even though we do not yet fully understand disease mechanisms; b) substantial progress has been made in identification of biomarkers; c) symptoms used to identify CHR are specific to psychotic illnesses; d) CHR diagnosis is not "extremely difficult"; e) the pattern of progression, although heterogenous, is discernible; f) "psychosis-like symptoms" are common but are not used to identify CHR; and g) on the point described as 'the real risk,' CHR diagnosis does not frequently cause harmful stigma.DiscussionMalhi et al.'s arguments do not fairly characterize progress in the CHR field nor efforts to minimize stigma. That said, much work remains in areas of consistent nomenclature, mechanisms of disease, dissecting heterogeneity, and biomarkers. With regard to what the authors term the "real risk" of stigma associated with a CHR "label," however, our view is that avoiding words like "risk" and "psychosis" reinforces the stigma that both they and we mean to oppose. Moreover, patients and their families benefit from being given a term that describes what is happening to them.

Background: Enlarged pituitary gland volume could be a marker of psychotic disorders. However, previous studies report conflicting results. To better understand the role of the pituitary gland in psychosis, we examined a large transdiagnostic sample of individuals with psychotic disorders. Methods: The study included 751 participants (174 with schizophrenia, 114 with schizoaffective disorder, 167 with psychotic bipolar disorder, and 296 healthy controls) across six sites in the Bipolar-Schizophrenia Network on Intermediate Phenotypes consortium. Structural magnetic resonance images were obtained, and pituitary gland volumes were measured using the MAGeT brain algorithm. Linear mixed models examined between-group differences with controls and among patient subgroups based on diagnosis, as well as how pituitary volumes were associated with symptom severity, cognitive function, antipsychotic dose, and illness duration. Results: Mean pituitary gland volume did not significantly differ between patients and controls. No significant effect of diagnosis was observed. Larger pituitary gland volume was associated with greater symptom severity (F = 13.61, p = 0.0002), lower cognitive function (F = 4.76, p = 0.03), and higher antipsychotic dose (F = 5.20, p = 0.02). Illness duration was not significantly associated with pituitary gland volume. When all variables were considered, only symptom severity significantly predicted pituitary gland volume (F = 7.54, p = 0.006). Conclusions: Although pituitary volumes were not increased in psychotic disorders, larger size may be a marker associated with more severe symptoms in the progression of psychosis. This finding helps clarify previous inconsistent reports and highlights the need for further research into pituitary gland-related factors in individuals with psychosis. [ABSTRACT FROM AUTHOR]

Home-based psychosocial care has the potential to improving outcomes in patients with schizophrenia and related disorders (SCZ). There is lack of India data for such care in early psychosis. We developed the " Saksham " programme, a bespoke self-managed home-based psychosocial care model, available in two formats: manual-based and mobile-application based. With the anticipated success of recruitment of early psychosis cases in our setting, we plan to test the such intervention in this population in future trials. To assess the feasibility of the Saksham programme intervention in people with SCZ and its clinical efficacy as an adjunct to treatment as usual. Seventy-five patient-caregiver pairs (total n=150) were recruited. Patients received either: treatment-as-usual (TAU) (n=25), manual-based Saksham intervention+TAU (n=25), or app-based Saksham intervention+TAU (n=25). Feasibility (i.e. acceptability, practicality, demand, implementation and integration) was assessed at three-months. Participants were assessed for psychopathology, illness-severity, cognition, functioning, disability, and caregiver-coping at baseline, one-month, and three-month. The percentage changes over time were compared across three groups. More found the mobile application-based intervention acceptable and easy-to-use than the manual-based intervention (92 % vs 68 %, and 76 % vs 68 %, respectively). Psychopathology and caregiver-burden improved significantly in all three groups (p<0.05). Cognition, disability, functioning, and caregiver burden improved significantly in the two Saksham intervention groups, with greater improvement in the Saksham app group (p<0.05). Home-based intervention is feasible and acceptable in a low-resource setting, with preliminary evidence for effectiveness. These findings need corroboration with randomised controlled trials in early psychosis to ameliorate course of illness. [ABSTRACT FROM AUTHOR]

Aim: To compare social, recreational and independent functioning among persons with psychosis across two geo‐cultural contexts, we adapted the well‐established Social Functioning Scale (SFS) and translated it into French and Tamil. We present the development and psychometric testing of this adaptation, the SFS‐Early Intervention. Methods: Sixteen items were added to reflect contemporary youth activities (e.g., online games) and 31 items adapted to enhance applicability and/or include context‐specific examples (e.g., 'church activity' replaced with 'religious/spiritual activity'). Psychometric properties and participant feedback were evaluated. Results: Test–retest reliability (ICCs) ranged from 0.813 to 0.964. Internal consistency (Cronbach's α) ranged from.749 to.936 across sites and languages. Correlations with original subscales were high. The scale was rated easy to complete and understand. Conclusions: The SFS‐Early Intervention is a promising patient‐reported measure of social, recreational and independent functioning. Our approach shows that conceptually sound existing measures are adaptable to different times and contexts. [ABSTRACT FROM AUTHOR]

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Copyright of Sante Mentale au Quebec is the property of Revue Sante Mentale au Quebec and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Prospective population studies suggest that psychotic syndromes may be an emergent phenomenon—a function of severity and complexity of more common mental health presentations and their nonpsychotic symptoms. Examining the relationship between nonpsychotic and subthreshold psychotic symptoms in individuals who later developed the ultimate outcome of interest, a first episode of psychosis (FEP), could provide valuable data to support or refute this conceptualization of how psychosis develops. We therefore conducted a detailed follow-back study consisting of semistructured interviews with 430 patients and families supplemented by chart reviews in a catchment-based sample of affective and nonaffective FEP. The onset and sequence of 27 pre-onset nonpsychotic (NPS) or subthreshold psychotic (STPS) symptoms was systematically characterized. Differences in proportions were analyzed with z -tests, and correlations were assessed with negative binomial regressions. Both the first psychiatric symptom (86.24% NPS) and the first prodromal symptom (66.51% NPS) were more likely to be NPS than STPS. Patients reporting pre-onset STPS had proportionally more of each NPS than did those without pre-onset STPS. Finally, there was a strong positive correlation between NPS counts (reflecting complexity) and STPS counts (β = 0.34, 95% CI [0.31, 0.38], P < 2 e-16). Prior to a FEP, NPS precede STPS, and greater complexity of NPS is associated with the presence and frequency of STPS. These findings complement recent arguments that the emergence of psychotic illness is better conceptualized as part of a continuum—with implications for understanding pluripotential developmental trajectories and strengthening early intervention paradigms. [ABSTRACT FROM AUTHOR]

Background: In the 1990s criteria were developed to detect individuals at high and imminent risk of developing a psychotic disorder. These are known as the at risk mental state, ultra high risk or clinical high risk criteria. Individuals meeting these criteria are symptomatic and help-seeking. Services for such individuals are now found worldwide. Recently Psychological Medicine published two articles that criticise these services and suggest that they should be dismantled or restructured. One paper also provides recommendations on how ARMS services should be operate. Methods: In this paper we draw on the existing literature in the field and present the perspective of some ARMS clinicians and researchers. Results: Many of the critics' arguments are refuted. Most of the recommendations included in the Moritz et al. paper are already occurring. Conclusions: ARMS services provide management of current problems, treatment to reduce risk of onset of psychotic disorder and monitoring of mental state, including attenuated psychotic symptoms. These symptoms are associated with a range of poor outcomes. It is important to assess them and track their trajectory over time. A new approach to detection of ARMS individuals can be considered that harnesses broad youth mental health services, such as headspace in Australia, Jigsaw in Ireland and ACCESS Open Minds in Canada. Attention should also be paid to the physical health of ARMS individuals. Far from needing to be dismantled we feel that the ARMS approach has much to offer to improve the health of young people. [ABSTRACT FROM AUTHOR]

Hippocampal circuitry has been posited to be fundamental to positive symptoms in psychosis, but its contributions to other factors important for outcome remains unclear. We hypothesized that longitudinal changes in the hippocampal circuit and concomitant changes of intracortical microstructure are altered in first episode psychosis (FEP) patients and that such changes are associated with negative symptoms and verbal memory. Longitudinal brain scans (2–4 visits over 3–15 months) were acquired for 27 FEP and 29 age‐ and sex‐matched healthy controls. Quantitative T1 maps, sensitive to myelin content, were used to sample the microstructure of the hippocampal subfields and output circuitry (fimbria, alveus, fornix, mammillary bodies), and intracortical regions. Dynamic anatomical covariance in pair‐wise regional trajectories were assessed for each subject, and graph theory was used to calculate a participation coefficient metric that quantifies the similarity/divergence between hippocampal and intracortical microstructure. The mean participation coefficient of the hippocampus was significantly reduced in FEP patients compared with controls, reflecting differences in output hippocampal regions. Importantly, lower participation coefficient of the hippocampal circuit was associated with worse negative symptoms, a relationship that was mediated by changes in verbal memory. This study provides evidence for reduced hippocampal centrality in FEP and concomitant changes in intracortical anatomy. Myelin‐rich output regions of the hippocampus may be an important biological trigger in early psychosis, with cascading effects on broader cortical networks and resultant clinical profiles. [ABSTRACT FROM AUTHOR]

Background: The first rate-limiting step for improving outcomes of psychosis through preventive interventions in people at clinical high risk for psychosis (CHR-P) is the ability to accurately detect individuals who are at risk for the development of this disorder. Currently, this detection power is sub-optimal. Methods: This is a conceptual and nonsystematic review of the literature, focusing on the work conducted by leading research teams in the field. The results will be structured in the following sections: understanding the CHR-P assessment, validity of the CHR-P as a universal risk state for psychosis, and improving the detection of at-risk individuals in secondary mental health care, in primary care, and in the community. Results: CHR-P instruments can provide adequate prognostic accuracy for the prediction of psychosis provided that they are employed in samples who have undergone risk enrichment during recruitment. This substantially limits their detection power in real-world settings. Furthermore, there is initial evidence that not all cases of psychosis onset are preceded by a CHR-P stage. A transdiagnostic individualized risk calculator could be used to automatically screen secondary mental health care medical notes to detect those at risk of psychosis and refer them to standard CHR-P assessment. Similar risk estimation tools for use in primary care are under development and promise to boost the detection of patients at risk in this setting. To improve the detection of young people who may be at risk of psychosis in the community, it is necessary to adopt digital and/or sequential screening approaches. These solutions are based on recent scientific evidence and have potential for implementation internationally. Conclusions: The best strategy to improve the detection of patients at risk for psychosis is to implement a clinical research program that integrates different but complementary detection approaches across community, primary, and secondary care. These solutions are based on recent scientific advancements in the development of risk estimation tools and e-health approaches and have the potential to be applied across different clinical settings. [ABSTRACT FROM AUTHOR]

Aim: While the course of psychopathology has been explored from an index mental health diagnosis onwards, there are few detailed, prospective studies of the occurrence of clinical psychopathology in youth with familial risk for severe mental illnesses such as psychosis. We sought to describe the appearance of Axis I psychopathology in a unique sample of adolescents with a family history of schizophrenia (FHR). Methods: One hundred and sixty two first‐ and second‐degree relatives (mean age 15.7 ± 3.6; range 8‐25) of probands with schizophrenia or schizoaffective disorder were assessed at baseline and annual intervals for up to 3 years, focusing on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM‐IV‐TR) Axis I psychopathology. Results: Fourteen individuals (8.6%) developed a psychotic disorder. One hundred and five subjects (65%) met criteria for an Axis I disorder over the course of the study, the most common of which was a depressive episode (40 subjects; 25%). Of the 148 individuals who did not develop psychosis, 91 (61%) had one or more Axis I disorders compared with 10/14 converters who had a comorbid Axis I disorder (71%). Ordered by increasing age of onset, diagnoses included cognitive and externalizing disorders, anxiety disorders, affective disorders, substance use disorders and psychotic disorders. Conclusions: In addition to an elevated risk of psychosis, young FHR relatives manifest a broad range of non‐psychotic Axis I psychopathology in childhood and adolescence. This breadth of diagnoses has implications for the structure and function of mental health services for young people. [ABSTRACT FROM AUTHOR]

Objective: Given the benefits of early intervention for psychosis and the social disengagement of youths not in education, employment, or training (NEET), this study sought to examine how being vocationally inactive (NEET) affects engagement in early intervention services. Both baseline vocational status and vocational trajectory in the first year of treatment were analyzed.Methods: Data from 394 patients of a Canadian early intervention service were analyzed using time-to-event and Cox proportional hazards regression analyses. Two-year disengagement rates were compared between patients who were vocationally inactive and active at baseline and between those who remained vocationally inactive until month 12 and those who were vocationally inactive only at baseline. Pertinent sociodemographic (age, sex, visible minority status, social and material deprivation indices, and family involvement), and clinical (duration of untreated psychosis, substance use disorder, medication nonadherence, and baseline positive and negative symptoms) factors were considered.Results: There was no statistically significant difference between the disengagement rates of those who were vocationally inactive (N=154) and those who were vocationally active (N=240) at baseline. Those who remained vocationally inactive at month 12 (N=77) were likelier to disengage in the second year than those who were vocationally inactive only at baseline (N=48) (χ2=5.44, df=1, p<0.05). This comparison remained significant in the regression analysis (hazard ratio [HR]=8.52, 95% confidence interval [95% CI]=1.54-47.1). The association of disengagement from services with lack of family contact with the treatment team (HR=3.91, 95% CI=0.98-15.6) and with greater material deprivation (HR=1.03, 95% CI=1.00-1.07) trended toward significance.Conclusions: The functional recovery of youths who are vocationally inactive when they enter services can affect their long-term service engagement and merits targeting by evidence-based interventions. [ABSTRACT FROM AUTHOR]

In this article, the authors discuss the need to improve the engagement of immigrant and ethnocultural minority population in Canada in early intervention services for psychosis. Topics include the move by the Mental Health Commission of Canada to prioritize the mental health of immigrants, refugees, ethnocultural groups, and racialized groups and the challenges confronted by mental health care system and service providers in fully engaging the said population groups.

Background: Young relatives of individuals with schizophrenia (i.e. youth at familial high-risk, FHR) are at increased risk of developing psychotic disorders, and show higher rates of psychiatric symptoms, cognitive and neurobiological abnormalities than non-relatives. It is not known whether overall exposure to environmental risk factors increases risk of conversion to psychosis in FHR subjects.Methods: Subjects consisted of a pilot longitudinal sample of 83 young FHR subjects. As a proof of principle, we examined whether an aggregate score of exposure to environmental risk factors, which we term a 'polyenviromic risk score' (PERS), could predict conversion to psychosis. The PERS combines known environmental risk factors including cannabis use, urbanicity, season of birth, paternal age, obstetric and perinatal complications, and various types of childhood adversity, each weighted by its odds ratio for association with psychosis in the literature.Results: A higher PERS was significantly associated with conversion to psychosis in young, familial high-risk subjects (OR=1.97, p=0.009). A model combining the PERS and clinical predictors had a sensitivity of 27% and specificity of 96%.Conclusion: An aggregate index of environmental risk may help predict conversion to psychosis in FHR subjects. [ABSTRACT FROM AUTHOR]

Aim Accurate prediction of which high-risk individuals will go on to develop psychosis would assist early intervention and prevention paradigms. We sought to review investigations of prospective psychosis prediction based on markers and variables examined in longitudinal familial high-risk ( FHR) studies. Methods We performed literature searches in Med Line, Pub Med and PsycINFO for articles assessing performance characteristics of predictive clinical tests in FHR studies of psychosis. Studies were included if they reported on one or more predictive variables in subjects at FHR for psychosis. We complemented this search strategy with references drawn from articles, reviews, book chapters and monographs. Results Across generations of FHR projects, predictive studies have investigated behavioural, cognitive, psychometric, clinical, neuroimaging and other markers. Recent analyses have incorporated multivariate and multi-domain approaches to risk ascertainment, with generally modest results. Conclusions Although a broad range of risk factors has been identified, no individual marker or combination of markers can at this time enable accurate prospective prediction of emerging psychosis for individuals at FHR. We outline the complex and multi-level nature of psychotic illness, the myriad of factors influencing its development, and methodological hurdles to accurate and reliable prediction. Prospects and challenges for future generations of FHR studies are discussed in the context of early detection and intervention strategies. [ABSTRACT FROM AUTHOR]

Abstract: Background: Accurate prediction of psychosis development in high-risk populations is an important but thus far elusive goal. Of the many diverse etiologic and risk factors identified thus far, few have been combined into prospective multivariate risk ascertainment models. We tested the predictive power of familial, neurobiological, socioenvironmental, cognitive and clinical risk factors through an integrative biopsychosocial model for emerging psychosis in young relatives at familial risk for schizophrenia. Methods: 96 young first- and second- degree relatives of schizophrenia probands were followed for an average of 2.38 (SD=0.98) years to examine their trajectory towards psychosis. Iterative structural equation modelling utilizing multiple etiologic and risk factors was employed to estimate their joint contribution to prediction of psychosis development. Results: The rate of conversion to psychosis over the study period was 12.5%. In the final model, clinical measures of schizotypy were directly predictive of conversion, with early (familial, biological, socioenvironmental) and cognitive risk factors indirectly predictive of psychosis through increased baseline clinical symptomatology. Our model provided an excellent fit to the observed data, with sensitivity of 0.17, specificity of 0.99, positive predictive value of 0.67 and negative predictive value of 0.89. Conclusions: Integrative modeling of multivariate data from familial, neurobiological, socioenvironmental, cognitive and clinical domains represents a powerful approach to prediction of psychosis development. The high specificity and low sensitivity found using a combination of such variables suggests that their utility may be in confirmatory testing among already selected high-risk individuals, rather than for initial screening. These findings also highlight the importance of data from a broad array of etiologic and risk factors, even within a familial high-risk population. With further refinement and validation, such methods could form key components of early detection, intervention and prevention programs. [Copyright &y& Elsevier]

Hallucinations are a core feature of psychosis, and their severity during the acute phase of illness is associated with a range of poor outcomes. Various clinical and sociodemographic factors may predict hallucinations and other positive psychotic symptoms in first episode psychosis (FEP). Despite this, the precise factors associated with hallucinations at first presentation to an early intervention service have not been extensively researched. Through detailed interviews and chart reviews, we investigated sociodemographic and clinical predictors in 636 minimally-medicated patients who entered PEPP-Montréal, an early intervention service for FEP, between 2003 and 2018. Hallucinations were measured using the Scale for the Assessment of Positive Symptoms (SAPS), while negative symptoms were assessed using the Scale for the Assessment of Negative symptoms (SANS). Depressive symptoms were evaluated through the Calgary Depression Scale for Schizophrenia (CDSS), and anxiety symptoms via the Hamilton Rating Scale for Anxiety (HAS). A majority (n = 381, 59.9 %) of the sample presented with clinically significant hallucinations (SAPS global hallucinations score ≥ 3) at program entry. These patients had an earlier age at onset, fewer years of education, and a higher severity of delusions, depression and negative symptoms than those without clinical-level hallucinations. These results suggest that individuals with clinically significant hallucinations at admission tend to be younger and have a greater overall symptom burden. This makes it especially important to monitor hallucinations alongside delusions, depression and negative symptoms in order to identify who might benefit from targeted interventions. The implications of these findings for early intervention and person-centered care are discussed. [ABSTRACT FROM AUTHOR]

Across subthreshold psychotic and nonpsychotic syndromes, symptoms experienced before the onset of a first episode of psychosis (FEP) may index distinct illness trajectories. We aimed to examine the associations between three types of pre-onset symptoms (self-harm, suicide attempts, and subthreshold psychotic) and outcome trajectories during FEP. Participants with FEP were recruited from PEPP-Montreal, a catchment-based early intervention service. Pre-onset symptoms were systematically assessed through interviews with participants (and their relatives) and reviews of health and social records. Over 2 years of follow-up at PEPP-Montreal, 3–8 repeated measures were collected for positive, negative, depressive, and anxiety symptoms, as well as functioning. We applied linear mixed models to examine associations between pre-onset symptoms and outcome trajectories. We found that on average over follow-up, participants with pre-onset self-harm had more severe positive, depressive, and anxiety symptoms compared with other participants (standardized mean differences: 0.32–0.76), while differences in negative symptoms and functioning were not significant. Associations did not differ by gender and remained similar after adjusting for the duration of untreated psychosis, substance use disorder, or baseline diagnosis of affective psychosis. Over time, depressive and anxiety symptoms improved among individuals with pre-onset self-harm, such that they converged with other individuals by the end of the follow-up. Similarly, pre-onset suicide attempts were associated with elevated depressive symptoms that improved over time. Pre-onset subthreshold psychotic symptoms were not associated with outcomes, except for a slightly different trajectory of functioning. Individuals with pre-onset self-harm or suicide attempts may benefit from early interventions that target their transsyndromic trajectories. General Scientific Summary: This study suggests that self-harm and suicide attempts before the onset of psychosis are associated with a more severe course of psychotic illness. Independently of their primary diagnoses, individuals with these pre-onset symptoms, relative to those without, seem to experience higher levels of depression and anxiety which then improve over the course of early intervention for psychosis. [ABSTRACT FROM AUTHOR]

Schizophrenia is an illness characterized by positive symptoms, negative symptoms, and cognitive impairments. Cognitive impairments occur before the onset of psychosis and could reflect glutamatergic dysregulation. Thus, identifying associations between genetic variations in genes coding for glutamatergic receptors and cognitive impairment in schizophrenia may help in understanding the basis of these deficits and in identifying potential drug targets. In a discovery cohort of 144 first-episode of psychosis patients (FEP), we genotyped 58 candidate Single Nucleotide Polymorphisms (SNPs) located in NMDA and metabotropic glutamatergic receptors. These SNPs were selected according to the results from the Psychiatric Genomic Consortium and were tested for association with intellectual quotient (IQ) as assessed with the Wechsler Intelligence Scales. For replication, we used the ICAAR cohort including 121 ultra-high-risk patients (UHR) with the same cognitive assessment. A polymorphism located in GRM7, rs1396409, was significantly associated with performance IQ in the discovery cohort of FEP. This association was replicated in the UHR cohort. This polymorphism is also associated with total IQ and verbal IQ in the merged dataset, with a predominant effect on the arithmetic subtest. The rs1396409 polymorphism is significantly associated with cognitive impairment during the onset of psychosis. This genetic association highlights the possible impact of glutamatergic genes in cognitive deficits in the early phases of psychosis and enforces the interest for new therapeutic interventions targeting the glutamatergic pathway. [ABSTRACT FROM AUTHOR]

Abstract: Background: Efforts to predict psychosis in individuals at high risk for schizophrenia have focused on the identification of sub-threshold clinical criteria and neurobiological markers, including neuropsychological assessment, structural and functional brain imaging, and psychophysiological testing. We sought to evaluate the relative utility of “psychosis-proneness” measures for prospective prediction of psychotic disorders in a group of young relatives at familial risk for schizophrenia. Methods: We examined the receiver operating characteristics of sub-threshold symptoms in predicting conversion to psychosis in a group of 97 young first- and second- degree relatives of persons with schizophrenia over a 2-year period. Towards this end, we utilized the Structured Interview of Prodromal Symptoms to derive measures of two of the four Scale of Prodromal Symptoms subscales (positive and disorganized) and the Chapman Magical Ideation and Perceptual Aberration scales. These four measures were, together, taken to reflect a putative index of psychosis-proneness. Results: Eleven of the 97 subjects developed a psychotic disorder over 2 years of follow-up. Seventeen of the 97 subjects tested positive on this index of psychosis-proneness at baseline and of these 10 converted to psychosis. The sensitivity and specificity of the test were 91 percent and 92 percent respectively. The positive predictive value of the test was 59 percent and its negative predictive value was 99 percent. Addition of measures of cognitive or social function to the index decreased its predictive ability, reducing its specificity and/or sensitivity. Conclusions: A relatively simple set of clinical measures can be utilized to prospectively identify familial high risk individuals who convert to psychosis with high specificity and sensitivity. Implications for the proposed addition of an “Attenuated Psychosis Syndrome” in DSM-5 are discussed. [Copyright &y& Elsevier]

Objective: Although early intervention (EI) programs for psychosis invest in clients remaining engaged in treatment, disengagement remains a concern. It is not entirely clear whether immigrants are likelier to disengage. The rates and predictors of disengagement for immigrant vis-à-vis non-immigrant clients in a Canadian EI setting were analyzed.Method: 297 clients were included in a time-to-event analysis with Cox Proportional Hazards regression models. Immigrant status (first- or second-generation immigrant or non-immigrant), age, gender, education, substance abuse, family contact, social and material deprivation and medication non-adherence were tested as predictors of service disengagement.Results: 24.2% (n=72) of the clients disengaged from services before completing two years. Disengagement rates did not differ between first-generation immigrants (23.3%), second-generation immigrants (22.7%) and non-immigrants (25.3%). For all clients, only medication non-adherence predicted disengagement (HR=3.81, 95% CI 2.37-6.14). For first-generation immigrants, age (HR=1.17, 95% CI 1.02-1.34) and medication non-adherence (HR=2.92, 95% CI 1.09-7.85) were significant predictors. For second-generation immigrants, material deprivation (HR=1.03, 95% CI 1.00-1.05) and medication non-adherence (HR=11.07, 95% CI 3.20-38.22) were significant.Conclusion: Disengagement rates may be similar between immigrants and non-immigrants, but their reasons for disengagement may differ. Medication adherence was an important predictor for all, but the role of various sociodemographic factors differed by group. Sustaining all clients' engagement in EI programs may therefore require multi-pronged approaches. [ABSTRACT FROM AUTHOR]

• This is the first study applying clinical high at-risk state criteria in an external site. • We show that help-seeking adolescents and young adults meet multiple CHARMS categories. • We show that depressive symptoms and functioning worsen when meeting criteria for multiple conmitant CHARMS categories, but not psychotic symptoms. • Psychotic symptoms explain poor functioning, and not depressive symptoms or CHARMS categories. We aim to assess how functioning, depressive symptoms, and psychotic symptoms are associated with different numbers of Clinical High At-Risk Mental State (CHARMS) categories. In this cross-sectional study, we assessed 62 help-seeking subjects aged 15-24 with a drop in functioning, with Structured Clinical Interview for DSM-5, Social and Occupational Functioning Assessment Scale (SOFAS), Comprehensive Assessment of At-Risk Mental State to define risk for psychosis, Hamilton Depression Rating scale (HAM-D), Positive and Negative Symptoms Scale, 6 items (PANSS-6). CHARMS criteria were assessed via retrospective chart review. Overall, 30.6% did not meet any CHARMS component criteria at baseline (CHARMS-), 27.4%, 33.9% and 8.1% met one, two, and three or more CHARMS groups. Overall, 48.8% met criteria for ultra-high risk for psychosis (17.7% without other CHARMS categories), 25.8% risk of borderline personality disorder (3.2% alone), 35.5% mild depression (8.1% alone), 11.3% risk of bipolar disorder (1.6% alone). SOFAS score and HAM-D score worsened from CHARMS- to three or more CHARMS categories, whilst PANSS-6 score did not. In a multivariate regression only PANSS-6 (beta=-1.105, p<0.001) was associated with SOFAS (R2=0.385). Help-seeking youth with poor functioning present symptoms meeting CHARMS criteria. Meeting criteria for multiple CHARMS categories is associated with increased depressive, but not psychotic symptoms, while psychotic symptoms play a prominent role in determining functional impairment. Results should be interpreted within the limitations of the study including the small sample size and the cross-sectional design, and need further replications. [ABSTRACT FROM AUTHOR]