Background and Hypotheses Research suggests that stress contributes to psychosis risk through an affective pathway, where heightened emotional responses to stressors lead to increased vulnerability. Specifically, individuals at clinical high-risk for psychosis (CHR-p) display more intense negative affect (NA) intensity, which is thought to exacerbate psychosis risk. The present study explored temporal dynamics between momentary NA intensity and delusional severity in CHR-p using ecological momentary assessment (EMA). Aims were to: (1) examine group differences in NA intensity and variability and (2) explore bidirectional associations between NA and attenuated delusions in the context of daily life. Study Design A sample of 120 CHR participants and 59 healthy controls completed 1 week of EMA surveys examining NA and attenuated delusions. Multilevel models examined time-lagged effects of NA reactivity on attenuated delusions and vice versa. Results Consistent with previous research, individuals at CHR displayed greater levels of NA intensity compared to healthy controls. Additionally, the CHR group exhibited variability affective changes throughout the day, suggesting a disrupted return to emotional homeostasis. Contrary to predictions, NA intensity did not predict subsequent delusional severity, highlighting potential complexities in the association that may be revealed by EMA methodologies. Instead, the study demonstrated that heightened attenuated delusional severity predicted subsequent increases in NA intensity. Conclusions These results demonstrated attenuated delusions exacerbate momentary elevations in NA intensity. Together with evidence from previous literature, findings underscore this relationship may be sensitive to the timescale of measurement, indicating the need for elucidating mechanisms underlying these associations to improve outcomes.

Importance:Cognition is impaired in people with schizophrenia, affecting quality of life and functioning. Therefore, it is important to understand and characterize this impairment. Objective:To update and revisit the evidence for a central processing speed impairment in people with schizophrenia and examine the factors that moderate this impairment. Data Sources:Articles were identified through the PubMed and PsycINFO databases from February 1, 2009, through November 2, 2023. Study Selection:Studies were included if they reported on a symbol coding test and at least 2 additional cognitive tests from 2 other cognitive domains, contrasted people with schizophrenia to controls, used contemporary diagnostic criteria, included sufficient detail to calculate Hedges g effect sizes, and were reported in English. Of 4530 identified articles, 115 studies met inclusion criteria. Data Extraction and Synthesis:This study followed the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) and Meta-Analysis of Observational Studies in Epidemiology (MOOSE) reporting guidelines. Means, SDs, and sample sizes were extracted for all cognitive tests that appeared in at least 3 of the 115 studies. Data were entered and visually checked by independent extractors. Data were generally pooled using random-effects models, except when specified. Measures of homogeneity (Q and I2) and publication bias (fail-safe N and funnel plots) were also examined. Main Outcomes and Measures:The primary outcome was the degree of cognitive impairment (Hedges g) observed for people with schizophrenia in 50 cognitive tests, focusing on symbol coding tests of processing speed. Further, this study aimed to identify clinical and study characteristics that moderate the degree of symbol coding impairment. Results:Data were available for 10 114 people with schizophrenia and 13 235 controls from 115 studies. Symbol coding tasks were among the most impaired (g = -1.52; 95% CI, -1.65 to -1.40) but did not reliably differ from 15 other tests. Intelligence quotient and age difference from controls, composition of sex assigned at birth, inpatient status, and whether the sample included schizoaffective and schizophreniform diagnoses all moderated the degree of symbol coding impairment. Conclusions and Relevance:This meta-analysis provides insight into the consistency of the processing speed impairment for people with schizophrenia. Findings support that this impairment may be central to global cognitive impairments, which might be a consequence of altered brain connectivity.

QuestionIs there continued evidence of a central processing speed deficit for people with schizophrenia?FindingsIn this systematic review and meta-analysis of 115 studies, symbol coding tests of processing speed remained among the most impaired cognitive tests for people with schizophrenia. Of the 49 other cognitive tests examined, symbol coding was reliably more impaired than 34 of them.MeaningThis study suggests that processing speed continues to emerge as a particularly impaired cognitive domain, and findings indicate there may be an underlying mechanism driving global cognitive impairment, such as altered brain connectivity, that processing speed is especially sensitive to. This meta-analysis provides an updated review of the evidence for a central processing speed impairment in people with schizophrenia. ImportanceCognition is impaired in people with schizophrenia, affecting quality of life and functioning. Therefore, it is important to understand and characterize this impairment.ObjectiveTo update and revisit the evidence for a central processing speed impairment in people with schizophrenia and examine the factors that moderate this impairment.Data SourcesArticles were identified through the PubMed and PsycINFO databases from February 1, 2009, through November 2, 2023.Study SelectionStudies were included if they reported on a symbol coding test and at least 2 additional cognitive tests from 2 other cognitive domains, contrasted people with schizophrenia to controls, used contemporary diagnostic criteria, included sufficient detail to calculate Hedges g effect sizes, and were reported in English. Of 4530 identified articles, 115 studies met inclusion criteria.Data Extraction and SynthesisThis study followed the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) and Meta-Analysis of Observational Studies in Epidemiology (MOOSE) reporting guidelines. Means, SDs, and sample sizes were extracted for all cognitive tests that appeared in at least 3 of the 115 studies. Data were entered and visually checked by independent extractors. Data were generally pooled using random-effects models, except when specified. Measures of homogeneity (Q and I2) and publication bias (fail-safe N and funnel plots) were also examined.Main Outcomes and MeasuresThe primary outcome was the degree of cognitive impairment (Hedges g) observed for people with schizophrenia in 50 cognitive tests, focusing on symbol coding tests of processing speed. Further, this study aimed to identify clinical and study characteristics that moderate the degree of symbol coding impairment.ResultsData were available for 10 114 people with schizophrenia and 13 235 controls from 115 studies. Symbol coding tasks were among the most impaired (g = -1.52; 95% CI, -1.65 to -1.40) but did not reliably differ from 15 other tests. Intelligence quotient and age difference from controls, composition of sex assigned at birth, inpatient status, and whether the sample included schizoaffective and schizophreniform diagnoses all moderated the degree of symbol coding impairment.Conclusions and RelevanceThis meta-analysis provides insight into the consistency of the processing speed impairment for people with schizophrenia. Findings support that this impairment may be central to global cognitive impairments, which might be a consequence of altered brain connectivity.

Epistemically suspect beliefs (ESBs) have deleterious effects on public health, social policy, political processes, and consensual understandings of the world. Although distinct fields' independent attempts to document and intervene on ESBs have yielded progress, increased cross talk with disciplines less regularly included in discussions and initiatives could accelerate innovation and translation of acquired knowledge into effective interventions. To encourage a more interdisciplinary, efficient, and effective approach, this commentary highlights insights and research directions that become apparent when integrating field-specific approaches and findings with the unique but relatively neglected perspective on ESBs offered by clinical psychology and psychiatry. (PsycInfo Database Record (c) 2026 APA, all rights reserved).

BACKGROUND AND HYPOTHESIS:Processing speed and verbal learning are linked to functioning in people at clinical high-risk for psychosis (CHR-P). However, a clear understanding of these relationships has been limited by the use of single-value assessor ratings of functioning and limited incorporation of self-report and longitudinal functional assessments. This study aims to examine the effect of processing speed and verbal learning on longitudinal assessor-rated and self-reported functioning. STUDY DESIGN:Individuals at CHR-P (n = 1282) and community controls (n = 425) who participated in Accelerating Medicines Partnership-Schizophrenia were examined. Processing speed and verbal learning abilities were ascertained using the Penn Computerized Neurocognitive Battery. Assessor-rated functioning was measured using the Global Functioning Scales. Self-reported functioning was collected using Ecological Momentary Assessment. Analyses were linear models and mixed-effects models. STUDY RESULTS:Both processing speed and verbal learning were associated with assessor-rated functioning at baseline and through 2 months (Ps < 0.001). Processing speed abilities predicted changes in self-reported ability to function (P = .036), motivation (P = .040), and concentration (P = .020) over time. Verbal learning abilities predicted changes in self-reported loneliness (P = .044) over time. Processing speed and verbal learning were associated with assessor-rated and self-reported functioning over and above estimated intelligence quotient and positive symptoms. CONCLUSIONS:Processing speed and verbal learning are important predictors of short-term longitudinal functioning, and may be important targets for early recognition and mitigation of psychosis risk.

This Viewpoint explores the current methods of predicting conversion to a psychotic disorder among individuals who are at high risk for psychosis and suggests alternative approaches that more accurately reflect the dynamics of this population.

Social networks provide critical support, yet individuals at clinical high-risk for psychosis (CHR) often experience deficits in social functioning and have smaller networks compared to healthy controls (HCs). Cognitive impairment, a hallmark characteristic of this group, may be associated with these challenges. This study is the first investigation into the relationships between general and specific domains of cognition and social network and communication abilities in people at CHR. The sample included 91 participants (HC = 43, CHR = 48) with complete cognitive and social network assessments from the same visit, with additional analyses including guardian ratings of social responsiveness and communication. Cognitive ability was significantly associated with social network size in both groups (b = 0.38, p < .0001), with significant contributions from working memory (b = 0.29, p = .004), speed of processing (b = 0.23, p = 002), verbal learning (b = 0.24, p = .007), and social cognition (b = 0.25, p = .012). Higher scores on cognitive functioning correlated with better social reciprocity (b = 1.28, p = .009) and fewer communication difficulties (b = 0.25, p < .002). Processing speed was particularly relevant to both social responsiveness (b = 0.88, p < .022) and communication difficulties (b = 0.12, p < .03). An interaction effect revealed that associations between cognitive ability on communication skills were more pronounced in CHR individuals compared to HCs (b = 0.26, p < .037). These findings underscore the potential role of specific cognitive domains, such as processing speed, in social functioning among CHR individuals. Future research should examine the directionality of these relationships to better understand underlying mechanisms of social functioning impairments and inform treatment development.

Background:Social cognitive impairments are common in individuals at clinical high-risk (CHR) for psychosis. Emotion recognition, a key component of social cognition, has been extensively examined in the CHR population, primarily with facial emotion recognition tasks, which have consistently demonstrated impairments. However, we have a limited understanding of whether the perception of broad bodily movements, known as biological motion processing (BM), contributes to emotion recognition impairment in this population. Methods:All participants completed the Point Light Walker (PLW) task, a paradigm that isolates body movement, to assess performance on BM processing. This study included 63 participants (34 CHR, 29 healthy controls (HC)). Symptom severity and functioning was measured by the Structured Interview for Prodromal Syndromes (SIPS), and the Negative Symptoms Inventory-Psychosis Risk (NSI-PR). Accuracy and response times (RTs) on the PLW were compared between groups using independent t-tests. Results:Linear regressions were used to examine associations with symptom severity. CHR individuals showed reduced fear recognition (p = 0.015), longer RTs when responding to videos depicting fear (p = 0.022), and longer RTs for incorrect fear responses after controlling for sex (p = 0.046). Alogia showed a positive trending association with BM emotion recognition (p = 0.076), but performance did not otherwise relate to other symptoms. Additional analyses examined sex-specific patterns, revealing interaction effects for neutral accuracy and RTs to anger-related stimuli. Conclusion:These findings suggest that CHR individuals may experience subtle impairments in recognizing fear and processing threat/high-arousal emotions. Consequently, impaired BM recognition and processing of fear might serve as an early indicator of psychosis risk.

Alterations in emotional functioning are a characteristic symptom of psychotic disorders. The clinical high-risk (CHR) period provides an important time for investigating early mechanisms, and their relation to psychosis vulnerability. However, our understanding of subjective emotional experiences in this critical population, particularly contextualized within social interactions, is limited. To address this gap, the present study aimed to evaluate subjective emotional experiences in CHR youth (12-30) using an experimental dyadic interaction paradigm. The sample included 148 individuals, 36 CHR-Partner dyads and 41 Control-Partner dyads, who engaged in three 10-min dyadic interactions (i.e., neutral, conflict, and pleasant). Following each conversation, participants reported the intensity of their positive and negative emotional experiences. Participants also completed a series of structured clinical interviews. CHR youth reported greater negative emotional experiences following pleasant conversations than control youth (U(74) = 533.5, p = 0.035). In CHR youth, greater negative emotional experiences following neutral conversations were associated with greater positive (rs = 0.37,pcorr = 0.046) and negative (rs = 0.44, pcorr = 0.038) psychosis-risk symptoms. Significant differences between CHR and control dyads were found for youth-partner discrepancies in positive emotional experiences following neutral (U(72) = 883, pcorr = 0.014) and conflict (t(72) = 3.28, p < 0.005) conversations as well as negative emotional experiences following neutral (U(72) = 914, p < 0.005) and pleasant (U(71) = 855.5, p = 0.043) conversations. Greater discrepancies in negative emotional experiences between CHR youth and partners following the neutral conversation were associated with greater negative symptoms (rs = -0.42, p < 0.05). These results provide understanding into mechanisms driving socioemotional functioning in CHR individuals and can inform interventions that target close relationships to improve outcomes.

Background and Hypothesis In accordance with the Cognitive Model of Negative Symptoms, defeatist performance beliefs (DPBs) are an important psychosocial mechanism of negative symptoms in schizophrenia-spectrum groups. DPBs are also mediators of negative symptom improvement in clinical trials. Despite the clinical significance of DPBs and their inclusion as a mechanism of change measure in clinical trials, the psychometric properties of the DPB scale have not been examined in any schizophrenia-spectrum group. Study Design This study evaluated the factor structure, reliability, and validity of the DPB scale in 943 schizophrenia and 250 clinical high-risk for psychosis (CHR) participants from multiple US sites. Confirmatory factor analyses tested competing factor structures: a unidimensional model—consistent with how DPBs are currently assessed—and multifactorial models with up to 4 factors identified with exploratory factor analyses. Study Results Models with 3 and 4 factors provided superior fit compared to the unidimensional model, with an advantage for the 3-factor model. The 3-factor model, consisting of Overvaluing Success, Overvaluing Failure, and Overvaluing Social Evaluation factors, demonstrated good replicability, temporal stability, and measurement invariance in schizophrenia and CHR samples. Convergent validity was demonstrated via significant correlations with negative symptoms and functioning, but limited associations were present with neurocognition. Discriminant validity was supported by low correlations with positive symptoms. Conclusions Findings support the validity and reliability of the 3-factor structure of the DPB scale across phases of psychosis. Use of a 3-factor structure may clarify the most critical DPB targets for negative symptom treatment and early prevention and intervention.

Spite sensitivity, or the fear that a person is willing to intentionally take a loss to ensure that another person will as well, may be a key component in understanding persecutory ideation (the belief that others want to harm you). We implemented a co-twin control design to examine potentially causal relationships among persecutory ideation, spite sensitivity, and neural activity and connectivity. Sixty-nine participants (23 monozygotic twin pairs and an additional 23 unpaired monozygotic twins) completed the Minnesota Trust Game-a social decision-making game played asynchronously with an anonymous partner that targets spite sensitivity by varying the incentives of the partner. Participants with more self-reported persecutory ideation (relative to those with lower persecutory ideation) trusted less even when the partner was incentivized to be fair. Similarly, computational modeling showed that increased persecutory ideation was associated with greater beliefs of a partner's spitefulness. Twins with greater beliefs of a partner's spitefulness (relative to their co-twins) also reported higher persecution. In addition, twin differences in left lateral OFC activation during the task were associated with spite sensitivity. These results point towards a potentially causal role of the lateral OFC on spite sensitivity, and in turn effects of spite sensitivity on persecutory ideation.

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.

Existing work indicates that there is unmet need for care in those at clinical high risk (CHR) for psychosis. However, research on the factors that drive treatment seeking behaviors in this population is limited. Further, it is unknown how help-seeking behavior in CHR individuals compares to those seen in mood disorders, who have a higher rate of treatment seeking behavior. Participants (n = 559) completed an assessment of their intent to seek mental health treatment, attenuated psychosis-risk symptoms, and psychiatric symptoms and diagnoses. Participants were divided into CHR (n = 91), Mood Disorders (MD) (n = 72), or Community Controls (CC) groups (n = 396), whose intent to seek treatment was compared. Associations between intent to seek treatment with past treatment, depression, anxiety, positive and negative symptoms, distress from symptoms, intelligence quotient (IQ) estimates, and insight were assessed in CHR individuals. Further, it was assessed how this differs for the MD group. The MD group reported higher intent to seek treatment than CHR individuals, which reported higher intent to seek treatment than the CC group. In those at CHR, previous treatment, greater depression and anxiety severity, and higher distress all independently predicted higher intent to seek treatment. Depression predicted intent to seek treatment in both MD and CHR individuals. Previous treatment predicted intent to seek treatment in those at CHR. Our findings suggest that depression and past treatment utilization are critical factors in increasing intent to seek treatment in those at CHR, potentially serving as important targets for engaging this population in treatment.

Reward processing is impaired in people with schizophrenia, which may begin in the clinical high-risk (CHR) for psychosis period. The Monetary Incentive Delay (MID) task has been important in understanding the neural correlates of reward processing deficits in various psychiatric disorders. Previous research has found that CHR individuals have an imprecise mental representation of rewards, which leads to a diminished differentiation between rewards, though this has not been observed behaviorally. A total of 19 CHR individuals and 20 controls were given a novel variant of the MID task, designed to examine how modulating reward context may impact responses to reward cues, a process often referred to as "adaptive coding." Both groups appeared to update their behavior in response to the rewards available in this adaptive task. However, when compared to controls who showed a more graded decrease in response time to increasing reward contexts, CHR individuals appeared to have a sharp decrease in response time in the low reward context that is nearly stable across higher reward contexts. This is largely driven by the exponential component of the response time distribution, which is often interpreted to be more cognitively or effortfully influenced. Response times are related to negative symptoms, but not positive symptoms, disorganized symptoms, or estimated intelligence. Although an adaptive coding effect was not observed, these results provide novel insight into the reward processing mechanisms and volitional processes in the CHR population, as this was the first study to observe the diminished differentiation of rewards behaviorally.

The clinical-high-risk for psychosis (CHR-P) syndrome is heterogeneous in terms of clinical presentation and outcomes. Identifying more homogenous subtypes of the syndrome may help clarify its etiology and improve the prediction of psychotic illness. This study applied latent class cluster analysis (LCCA) to symptom ratings from the North American Prodrome Longitudinal Studies 1 and 2 (NAPLS 1 and 2). These analyses produced evidence for three to five subgroups within the CHR-P syndrome. Differences in negative and disorganized symptoms distinguished among the subgroups. Subgroup membership was found to predict conversion to psychosis. The authors contrast the methods employed within this study with previous attempts to identify more homogenous subgroups of CHR-P individuals and discuss how these results could be tested in future samples of CHR-P individuals.

Background and Hypothesis:Processing speed dysfunction is a core feature of psychosis and predictive of conversion in individuals at clinical high risk (CHR) for psychosis. Although traditionally measured with pen-and-paper tasks, computerized digit symbol tasks are needed to meet the increasing demand for remote assessments. Therefore we: (1) assessed the relationship between traditional and computerized processing speed measurements; (2) compared effect sizes of impairment for progressive and persistent subgroups of CHR individuals on these tasks; and (3) explored causes contributing to task performance differences. Study Design:Participants included 92 CHR individuals and 60 healthy controls who completed clinical interviews, the Brief Assessment of Cognition in Schizophrenia Symbol Coding test, the computerized TestMyBrain Digit Symbol Matching Test, a finger-tapping task, and a self-reported motor abilities measure. Correlations, Hedges' g, and linear models were utilized, respectively, to achieve the above aims. Study Results:Task performance was strongly correlated (r = 0.505). A similar degree of impairment was seen between progressive (g = -0.541) and persistent (g = -0.417) groups on the paper version. The computerized task uniquely identified impairment for progressive individuals (g = -477), as the persistent group performed similarly to controls (g = -0.184). Motor abilities were related to the computerized version, but the paper version was more related to symptoms and psychosis risk level. Conclusions:The paper symbol coding task measures impairment throughout the CHR state, while the computerized version only identifies impairment in those with worsening symptomatology. These results may be reflective of sensitivity differences, an artifact of existing subgroups, or evidence of mechanistic differences.

BACKGROUND: Spite sensitivity provides a valuable construct to understand persecutory ideation and its underlying neural mechanisms. We examined the relationship between persecution and spite sensitivity in psychosis to identify their neural substrates. METHODS: In a 3T magnetic resonance imaging scanner, 49 participants with psychosis played the Minnesota Trust Game, in which they decided whether to take a small amount of money or trust a partner to choose between fair and unfair distributions of money. In some conditions, the partner benefited from the unfair option, while in others, the partner lost money. Participants who were untrusting in the second condition (suspiciousness) showed heightened sensitivity to spite. Behavioral measures included mistrust during the 2 conditions of the game, which were compared with Brief Psychiatric Rating Scale persecution and computational modeling. Functional connectivity and blood oxygen level-dependent analyses were also conducted on a priori regions during spite-sensitive decisions. RESULTS: Behavioral results replicated previous findings; participants who experienced more persecutory ideation trusted less, specifically in the suspiciousness condition. Functional connectivity findings showed that decreased connectivity between the orbitofrontal cortex-insula and the left frontoparietal network was associated with increased persecutory ideation and estimated spite-guilt (a marker of spite sensitivity). Additionally, we found differences between conditions in caudate nucleus, medial prefrontal cortex, and lateral orbitofrontal cortex activation. CONCLUSIONS: These findings provide a new perspective on the origin of positive symptoms by identifying primary brain circuits that are related to both spite sensitivity and persecutory ideation.

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.