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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.

Psychotic-like experiences (PLEs) may reflect elevated risk for serious mental illness, including psychosis. Although some studies report an association between PLEs and increased service utilization, there is evidence of unmet need among individuals with PLEs, with few studies exploring the relation between PLEs and intent to seek treatment. Characterizing factors that underlie intent to seek treatment in individuals not otherwise engaged in treatment may assist in determining the role of PLEs and future intentions, and help prioritize symptoms of greatest significance. Non-help-seeking participants ages 16-30 years (nanalysis = 2529) in a multi-site study completed online questionnaires of PLEs (PRIME with distress), depression (CESD), anxiety (STAI), and intention to seek mental health treatment. Associations between PLEs and intent to seek treatment were analyzed through multiple linear regressions. PRIME scores predicted intent to seek treatment, and item-level analyses suggested that this association was driven by items 12 (going crazy), 7 (wondering if people may hurt me), 5 (confused if things are real or imagination/dreams), and 1 (odd/unusual things going on). When accounting for the effects of anxiety and depression, PLE sum scores as well as individual experiences remained statistically significant, although effect sizes were negligible. Findings suggest that PLEs can play a role in identifying individuals who intend to seek mental health services and warrant further research in independent samples.

BACKGROUND AND HYPOTHESES: Psychosis-risk inventories, like the Structured Interview for Psychosis-Risk Syndromes (SIPS), utilize symptom components and coalesce the information into a single-severity rating. These components include frequency, duration, in-the-moment conviction, retrospective insight, distress, and effect on social/role functioning. While combining components distills a great deal of important information into one practical symptom rating, this approach may mask important details of the greater clinical picture. STUDY DESIGN: Individuals at clinical high risk for psychosis (n = 115) were assessed with the SIPS Score Separable Components (SSSC) scale, created to accompany the SIPS positive items by dividing each item into the 7 components identified above. The latent structure of the SSSC was identified with an exploratory factor analysis (EFA). The factors were followed up with validation analyses including hypothesized cognitive, functioning, and symptom measures. Finally, clinical utility analyses were conducted to understand relationships between psychosis risk and common comorbidities. STUDY RESULTS: EFA revealed that the SSSC had 3 interpretable factors with the appropriate fit (rmsr = 0.018, TLI = 0.921): Conviction (in-the-moment conviction, retrospective insight), Distress-Impairment (distress, social/role functioning), and Frequency/Duration (frequency, duration). Conviction was minimally valid, Distress-Impairment had excellent validity, and Frequency/Duration was not related to any of the candidate validators. Conviction significantly predicted elevated psychosis risk. Distress-Impairment was related to common comorbid symptoms. Notably, the factors associated more strongly with clinical features than the traditional SIPS scores. CONCLUSIONS: The SSSC offers a supplemental approach to single-severity ratings, providing useful clinical insight, mechanistic understanding, and the potential for better capturing heterogeneity in this population.

BackgroundSince its inception, research in the clinical high-risk (CHR) phase of psychosis has included identifying and exploring the impact of relevant socio-demographic factors. Employing a narrative review approach and highlighting work from the United States, sociocultural and contextual factors potentially affecting the screening, assessment, and service utilization of youth at CHR were reviewed from the current literature.ResultsExisting literature suggests that contextual factors impact the predictive performance of widely used psychosis-risk screening tools and may introduce systemic bias and challenges to differential diagnosis in clinical assessment. Factors reviewed include racialized identity, discrimination, neighborhood context, trauma, immigration status, gender identity, sexual orientation, and age. Furthermore, racialized identity and traumatic experiences appear related to symptom severity and service utilization among this population.ConclusionsCollectively, a growing body of research from the United States and beyond suggests that considering context in psychosis-risk assessment can provide a more accurate appraisal of the nature of risk for psychosis, render more accurate results improving the field's prediction of conversion to psychosis, and enhance our understanding of psychosis-risk trajectories. More work is needed in the U.S. and across the globe to uncover how structural racism and systemic biases impact screening, assessment, treatment, and clinical and functional outcomes for those at CHR.

Suicide is a leading cause of death among youth on the psychosis spectrum. Internalized mental health stigma is one risk factor for suicide that may be particularly salient for youth with psychosis-risk syndromes and early psychosis. Among this population, Black youth may face exposure to racism-related stressors that may exacerbate the negative effects of internalized stigma. This study examined whether internalized stigma and race interact to predict suicidal thoughts and behaviors (STB) in a help-seeking sample of Black and White adolescents with psychosis-risk syndromes and early psychosis. Findings suggest that Black youth with early psychosis spectrum disorders may be particularly vulnerable to the negative effects of internalized stigma as they pertain to STB. Internalized stigma may therefore represent an important treatment target in suicide prevention efforts among this population.

AIM: Outcomes for individuals with psychotic disorders can be improved through early intervention services; however, identification continues to be a major problem in connecting individuals with these services. Social workers form a vast majority of the human service and mental health workforce in the United States and therefore have the potential to play a unique role in identifying and referring those who may benefit from specialty early intervention services. METHODS: The current article describes the methodological design, implementation, and participant recruitment procedures of a large-scale, web-based training program for social workers promoting identification and referral of individuals with emerging symptoms of a mental illness with psychosis in the context of a randomized clinical trial. RESULTS: The web-based study enrolled 1384 individuals. More than half of study participants enrolled within the first 3 months of the 14-month recruitment period. Completion of all study components was achieved by 959 individuals (69% of total enrolled), and completion status did not vary significantly by gender, ethnicity, or facility at which the individual was employed. Completion rates varied by race, such that participants identifying as White were more likely to complete the study, while those identifying as Black were less likely. DISCUSSION: The results suggest the feasibility of using a web-based training program to engage social workers in early psychosis identification practices. Challenges related to encouraging participants to complete the training and lessons learned during the study recruitment are discussed.

Dysfunction in the neural circuits underlying salience signaling is implicated in symptoms of psychosis and may predict conversion to a psychotic disorder in youth at clinical high risk (CHR) for psychosis. Additionally, negative symptom severity, including consummatory and anticipatory aspects of anhedonia, may predict functional outcome in individuals with schizophrenia-spectrum disorders. However, it is unclear whether anhedonia is related to the ability to attribute incentive salience to stimuli (through reinforcement learning [RL]) and whether measures of anhedonia and RL predict functional outcome in a younger, help-seeking population. We administered the Salience Attribution Test (SAT) to 33 participants who met criteria for either CHR or a recent-onset psychotic disorder and 29 help-seeking youth with nonpsychotic disorders. In the SAT, participants must identify relevant and irrelevant stimulus dimensions and be sensitive to different reinforcement probabilities for the 2 levels of the relevant dimension ("adaptive salience"). Adaptive salience attribution was positively related to both consummatory pleasure and functioning in the full sample. Analyses also revealed an indirect effect of adaptive salience on the relation between consummatory pleasure and both role (αβ = .22, 95% CI = 0.02, 0.48) and social functioning (αβ = .14, 95% CI = 0.02, 0.30). These findings suggest a distinct pathway to poor global functioning in help-seeking youth, via impaired reward sensitivity and RL.

The authors examine U.S.-based evidence that connects characteristics of the social environment with outcomes across the psychosis continuum, from psychotic experiences to schizophrenia. The notion that inequitable social and economic systems of society significantly influence psychosis risk through proxies, such as racial minority and immigrant statuses, has been studied more extensively in European countries. While there are existing international reviews of social determinants of psychosis, none to the authors' knowledge focus on factors in the U.S. context specifically-an omission that leaves domestic treatment development and prevention efforts incomplete and underinformed. In this review, the authors first describe how a legacy of structural racism in the United States has shaped the social gradient, highlighting consequential racial inequities in environmental conditions. The authors offer a hypothesized model linking structural racism with psychosis risk through interwoven intermediary factors based on existing theoretical models and a review of the literature. Neighborhood factors, cumulative trauma and stress, and prenatal and perinatal complications were three key areas selected for review because they reflect social and environmental conditions that may affect psychosis risk through a common pathway shaped by structural racism. The authors describe evidence showing that Black and Latino people in the United States suffer disproportionately from risk factors within these three key areas, in large part as a result of racial discrimination and social disadvantage. This broad focus on individual and community factors is intended to provide a consolidated space to review this growing body of research and to guide continued inquiries into social determinants of psychosis in U.S. contexts.

People with schizophrenia often experience a profound lack of motivation for social affiliation-a facet of negative symptoms that detrimentally impairs functioning. However, the mechanisms underlying social affiliative deficits remain poorly understood, particularly under realistic social contexts. Here, we investigated subjective reports and electroencephalography (EEG) functional connectivity in schizophrenia during a live social interaction. Individuals with schizophrenia (n = 16) and healthy controls (n = 29) completed a face-to-face interaction with a confederate while having EEG recorded. Participants were randomly assigned to either a Closeness condition designed to elicit feelings of closeness through self-disclosure or a Small-Talk condition with minimal disclosure. Compared to controls, patients reported lower positive emotional experiences and feelings of closeness across conditions, but they showed comparably greater subjective affiliative responses for the Closeness (vs. Small-Talk) condition. Additionally, patients in the Closeness (vs. Small-Talk) condition displayed a global increase in connectivity in theta and alpha frequency bands that was not observed for controls. Importantly, greater theta and alpha connectivity was associated with greater subjective affiliative responding, greater negative symptoms, and lower disorganized symptoms in patients. Collectively, findings indicate that patients, because of pronounced negative symptoms, utilized a less efficient, top-down mediated strategy to process social affiliation.

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.

Evidence supports the use of brief psychosis-spectrum screening tools for identifying individuals at an increased risk of developing a psychotic disorder. Screening has not been well studied in general mental health settings that serve young adults in the age range associated with highest risk for psychosis. This study explored the feasibility of psychosis-risk screening and assessment among help-seeking students at a university counseling center. The PRIME Screen-Revised was administered to students at clinic intake. Participants who screened positively were offered a follow-up assessment using the Structured Interview for Psychosis-risk Syndromes (SIPS). At intake, 510 students completed the PRIME Screen-Revised, with 132 (25.9%) screening positive. Comprehensive psychosis-spectrum evaluations were completed with 38 participants, and 22 met criteria for a psychosis-spectrum disorder, representing 57.9% of this subsample. Findings suggest that psychosis-risk screening in a college clinic is a promising approach to identifying those at high risk for or in the early stages of psychosis.

Objective: Untreated mental health (MH) concerns have significant implications for college students. This study examined the efficacy of a video contact intervention targeting students' intentions to seek counseling. Participants: One-hundred and sixty-three college students (M[superscript age] = 21.05, SD = 2.20) from a Mid-Atlantic university participated. The sample was predominantly female (74%). Method: Students were randomly assigned to view a student-targeted contact video (ie, clips from college students who share their mental health experiences), a MH comparison contact video, or a non-MH comparison video. Intentions to seek counseling and psychological distress were measured pretest and post-test. Results: Intentions to seek counseling significantly increased from pretest to post-test in the student-targeted contact video condition (F[1, 156] = 22.75, p < 0.001, partial [eta][superscript 2] = 0.13), but not in the comparison conditions. Further, this effect was only observed among participants who reported preexisting psychological distress (F[1, 153] = 28.00, p < 0.001, partial [eta][superscript 2] = 0.16). Conclusions: This study provides initial support for the utility of a student-targeted contact intervention video for increasing help-seeking intentions among those reporting current psychological distress.

Early detection and prevention of psychosis has become an international priority. Much of this work has focused on youth presenting with attenuated symptoms of psychosis-those at Clinical High Risk for psychosis (CHR)-given their elevated probability of developing the full disorder in subsequent years. Individuals at CHR may be prone to exacerbated psychological distress during the COVID-19 pandemic and its subsequent physical isolation measures, due to heightened stress sensitivity and comorbid mental health problems. Telepsychotherapy holds promise for reaching this population, especially during the current COVID-19 outbreak. However, there are limited evidence-based guidelines or interventions for use of telepsychotherapy with this population. In this paper, we review common clinical issues for individuals at CHR and how they might be exacerbated by the COVID-19 pandemic; best practices for treatment and adaptations for telepsychotherapy for individuals at CHR; and highlight real clinical issues that we are currently experiencing in a United States-based specialized CHR clinic as we conduct telepsychotherapy via videoconferencing. We conclude with questions for those in the field to contemplate, as well as potential challenges and benefits in using telepsychotherapy with individuals at CHR and their families.

The prediction error account of delusions has had success. However, its explanation of delusions with different contents has been lacking. Persecutory delusions and paranoia are the common unfounded beliefs that others have harmful intentions towards us. Other delusions include believing that one's thoughts or actions are under external control or that events in the world have specific personal meaning. We compare learning in two different cognitive tasks, probabilistic reversal learning and Kamin blocking, that have relationships to paranoid and non-paranoid delusion-like beliefs, respectively. We find that clinical high-risk status alone does not result in different behavioural results in the probabilistic reversal learning task but that an individual's level of paranoia is associated with excessive switching behaviour. During the Kamin blocking task, paranoid individuals learned inappropriately about the blocked cue. However, they also had decreased learning about the control cue, suggesting more general learning impairments. Non-paranoid delusion-like belief conviction (but not paranoia) was associated with aberrant learning about the blocked cue but intact learning about the control cue, suggesting specific impairments in learning related to cue combination. We fit task-specific computational models separately to behavioural data to explore how latent parameters vary within individuals between tasks and how they can explain symptom-specific effects. We find that paranoia is associated with low learning rates in the probabilistic reversal learning task and the blocking task. Non-paranoid delusion-like belief conviction is instead related to parameters controlling the degree and direction of similarity between cue updating during simultaneous cue presentation. These results suggest that paranoia and other delusion-like beliefs involve dissociable deficits in learning and belief updating, which, given the transdiagnostic status of paranoia, might have differential utility in predicting psychosis. [ABSTRACT FROM AUTHOR]

Autism and psychosis share overlapping clinical features and can occur comorbidly. Given growing recognition that early identification of psychosis risk symptoms may lead to better functional outcomes, the field needs valid tools for use in the assessment of psychosis risk symptoms within autism. This study employed a multi-method approach to evaluate the utility of a psychosis risk assessment tool, the Structured Interview for Psychosis-Risk Syndromes, for use with adolescents with autism. A total of 43 adolescents (N=21 with autism, N=22 typically developing) were interviewed using the positive symptom domain of the Structured Interview for Psychosis-Risk Syndromes. Study participant answers to interview questions were coded for verbal and behavioral responses, and error rates were compared between groups. Results indicate that adolescents with autism (all of whom had intact language skills) did not significantly differ from typically developing peers when answering questions about positive psychosis risk symptoms. A majority of verbal responses (93%) and behavioral responses (89%) to Structured Interview for Psychosis-Risk Syndrome items were rated as adequate for both groups, suggesting that the positive domain items from the Structured Interview for Psychosis-Risk Syndromes can be used with adolescents with autism. Regardless of diagnosis, higher rates of response errors were significantly correlated with greater difficulty understanding ambiguous language and increased interview times. Structured Interview for Psychosis-Risk Syndrome interviewers are cautioned to use follow-up probes to clarify items that might be confusing to participants and/or have higher response error rates for all adolescents, irrespective of autism status, to prevent false-positive responses for people with and without autism.

This systematic review and meta-analysis investigates if ethnoracial groups in the US differ in risk of schizophrenia and other psychotic disorders, clinical high risk for psychosis, and psychotic symptoms and experiences. Key Points: Question: Do ethnoracial groups in the US differ in risk of schizophrenia and other psychotic disorders, clinical high risk for psychosis (CHR-P), and psychotic symptoms (PSs) and experiences (PEs)? Findings: In this systematic review and meta-analysis including 64 studies of which 47 studies were included in the meta-analysis, risk of schizophrenia diagnosis was significantly increased among Black individuals and those categorized as other ethnoracial group compared with White individuals, and risk of PSs/PEs was significantly increased among both Black and Latinx groups. Findings regarding CHR-P were equivocal. Meaning: Ethnoracial risk variation in the US is present across multiple psychosis-related outcomes, suggesting that factors other than diagnostic bias alone underlie these disparities. Importance: Studies suggest a higher risk of schizophrenia diagnoses in Black vs White Americans, yet a systematic investigation of disparities that include other ethnoracial groups and multiple outcomes on the psychosis continuum is lacking. Objective: To identify ethnoracial risk variation in the US across 3 psychosis continuum outcomes (ie, schizophrenia and other psychotic disorders, clinical high risk for psychosis [CHR-P], and psychotic symptoms [PSs] and psychotic experiences [PEs]). Data Sources: PubMed, PsycINFO and Embase were searched up to December 2022. Study Selection: Observational studies on ethnoracial differences in risk of 3 psychosis outcomes. Data Extraction and Synthesis: Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed. Using a random-effects model, estimates for ethnoracial differences in schizophrenia and PSs/PEs were pooled and moderation by sampling and setting was determined, along with the assessment of heterogeneity and risk of bias. Main Outcomes and Measures: Risk of schizophrenia and other psychotic disorder, CHR-P, and conversion to psychosis among CHR-P and PSs/PEs. Results: Of 64 studies in the systematic review, 47 were included in the meta-analysis comprising 54 929 people with schizophrenia and 223 097 with data on PSs/PEs. Compared with White individuals, Black individuals had increased risk of schizophrenia (pooled odds ratio [OR], 2.07; 95% CI, 1.64-2.61) and PSs/PEs (pooled standardized mean difference [SMD], 0.10; 95% CI, 0.03-0.16), Latinx individuals had higher risk of PSs/PEs (pooled SMD, 0.15; 95% CI, 0.08-0.22), and individuals classified as other ethnoracial group were at significantly higher risk of schizophrenia than White individuals (pooled OR, 1.81; 95% CI, 1.31-2.50). The results regarding CHR-P studies were mixed and inconsistent. Sensitivity analyses showed elevated odds of schizophrenia in Asian individuals in inpatient settings (pooled OR, 1.84; 95% CI, 1.19-2.84) and increased risk of PEs among Asian compared with White individuals, specifically in college samples (pooled SMD, 0.16; 95% CI, 0.02-0.29). Heterogeneity across studies was high, and there was substantial risk of bias in most studies. Conclusions and Relevance: Findings of this systematic review and meta-analysis revealed widespread ethnoracial risk variation across multiple psychosis outcomes. In addition to diagnostic, measurement, and hospital bias, systemic influences such as structural racism should be considered as drivers of ethnoracial disparities in outcomes across the psychosis continuum in the US. [ABSTRACT FROM AUTHOR]