In vivo structural connectivity of the reward system along the hippocampal long axis.

Recent work has identified a critical role for the hippocampus in reward-sensitive behaviors, including motivated memory, reinforcement learning, and decision-making. Animal histology and human functional neuroimaging have shown that brain regions involved in reward processing and motivation are more interconnected with the ventral/anterior hippocampus. However, direct evidence examining gradients of structural connectivity between reward regions and the hippocampus in humans is lacking. The present study used diffusion MRI (dMRI) and probabilistic tractography to quantify the structural connectivity of the hippocampus with key reward processing regions in vivo. Using a large sample of subjects (N = 628) from the human connectome dMRI data release, we found that connectivity profiles with the hippocampus varied widely between different regions of the reward circuit. While the dopaminergic midbrain (ventral tegmental area) showed stronger connectivity with the anterior versus posterior hippocampus, the ventromedial prefrontal cortex showed stronger connectivity with the posterior hippocampus. The limbic (ventral) striatum demonstrated a more homogeneous connectivity profile along the hippocampal long axis. This is the first study to generate a probabilistic atlas of the hippocampal structural connectivity with reward-related networks, which is essential to investigating how these circuits contribute to normative adaptive behavior and maladaptive behaviors in psychiatric illness. These findings describe nuanced structural connectivity that sets the foundation to better understand how the hippocampus influences reward-guided behavior in humans.

Developmental changes in the endorsement of psychotic-like experiences from middle childhood through young adulthood.

BACKGROUND: Children tend to endorse psychotic-like experiences (PLEs) at higher rates than adults, although little is known about how specific symptom endorsement changes across the span of development. Here we take an observational approach to examine trends in PLE endorsement by age in two non-clinical samples: one of school-aged children and another of late adolescents and early adults. METHODS: Prodromal Questionnaire-Brief (child and adult versions) responses were investigated in individuals ages 9-13 (n = 11865) and 16-24 (n = 3209) from the Adolescent Brain and Cognitive Development Study (ABCD) and the Multisite Assessment of Psychosis-risk Study (MAP), respectively. Item-level endorsement and distressing item frequencies were examined by age throughout both cohorts. RESULTS: Unusual perceptual experiences were generally endorsed more heavily in childhood, while other PLEs were endorsed in adolescents and adults up to 4.8 times more frequently than in children. Additionally, certain experiences were endorsed by as many as 73 percent of the older sample. CONCLUSIONS: Considerations for the measurement of PLEs in childhood and adolescence are underscored. Findings from these two samples provide a window into the course of these PLEs and may serve as a scaffold for future research investigating normative versus risk-related experiences during development.

Prenatal maternal Inflammation, childhood cognition and adolescent depressive symptoms.

BACKGROUND: Accumulating evidence indicates that higher prenatal maternal inflammation is associated with increased depression risk in adolescent and adult-aged offspring. Prenatal maternal inflammation (PNMI) may increase the likelihood for offspring to have lower cognitive performance, which, in turn, may heighten risk for depression onset. Therefore, this study explored the potential mediating role of childhood cognitive performance in the relationship between PNMI and adolescent depressive symptoms in offspring. METHODS: Participants included 696 mother-offspring dyads from the Child Health and Development Studies (CHDS) cohort. Biomarkers of maternal inflammation [interleukin (IL)-6, IL-8, IL-1 receptor antagonist (IL-1RA) and soluble TNF receptor-II (sTNF-RII)] were assayed from first (T1) and second trimester (T2) sera. Childhood (ages 9-11) cognitive performance was assessed via standardized Peabody Picture Vocabulary Test (PPVT), a measure of receptive vocabulary correlated with general intelligence. Adolescent (ages 15-17) depressive symptoms were assessed via self-report. RESULTS: There were no significant associations between T1 biomarkers and childhood PPVT or adolescent depressive symptoms. Higher T2 IL1-RA was directly associated with lower childhood PPVT (b = -0.21, SE = 0.08, t = -2.55, p = 0.01), but not with adolescent depressive symptoms. T2 IL-6 was not directly associated with childhood PPVT, but higher T2 IL-6 was directly associated at borderline significance with greater depressive symptoms in adolescence (b = 0.05, SE = 0.03, t = 1.96, p = 0.05). Lower childhood PPVT predicted significantly higher adolescent depressive symptoms (b = -0.07, SE = 0.02, t = -2.99, p < 0.01). There was a significant indirect effect of T2 IL-1RA on adolescent depressive symptoms via childhood PPVT (b = 0.03, 95 % CI = 0.002-0.03) indicating a partially mediated effect. No significant associations were found with T2 sTNF-RII nor IL-8. CONCLUSIONS: Lower childhood cognitive performance, such as that indicated by a lower PPVT score, represents a potential mechanism through which prenatal maternal inflammation contributes to adolescent depression risk in offspring.

Mapping Psychosis Risk States onto the Hierarchical Taxonomy of Psychopathology Using Hierarchical Symptom Dimensions.

Clinical high risk for psychosis (CHR) is a transdiagnostic risk state. However, it is unclear how risk states such as CHR fit within broad transdiagnostic models such as the Hierarchical Taxonomy of Psychopathology (HiTOP). In this study, a hierarchical dimensional symptom structure was defined by unfolding factor analysis of self-report data from 3,460 young adults (mage=20.3). A subsample (n=436) completed clinical interviews, 85 of whom met CHR criteria. Regression models examined relationships between symptom dimensions, CHR status, and clinician-rated symptoms. CHR status was best explained by a reality distortion dimension, with contributions from internalizing dimensions. Positive and negative attenuated psychotic symptoms were best explained by multiple psychotic and nonpsychotic symptom dimensions including reality distortion, distress, fear, detachment, and mania. Attenuated psychotic symptoms are a complex presenting problem warranting comprehensive assessment. HiTOP can provide both diagnostic precision and broad transdiagnostic coverage, making it a valuable resource for use with at-risk individuals.

Different learning aberrations relate to delusion-like beliefs with different contents.

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 on two different cognitive tasks, probabilistic reversal learning (PRL) 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 behavioral results on the PRL task but that an individual's level of paranoia is associated with excessive switching behavior. 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 behavioral 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 on the PRL task as well as the blocking task. Non-paranoid delusion-like belief conviction was 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 - may have differential utility in predicting psychosis.

Factors impacting intent to seek treatment within youth at clinical high risk for psychosis.

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.

Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ): Rationale and Study Design of the Largest Global Prospective Cohort Study of Clinical High Risk for Psychosis.

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.

Chronic inflammation is associated with worsening working memory performance: Preliminary evidence from a diverse, longitudinal cohort of adolescents and young adults.

Many depressed individuals experience cognitive difficulties that persist when depression is in remission. Inflammation is hypothesized to play a role in cognitive dysfunction in depression; however, many aspects of this relationship are not well characterized. The current study examined whether inflammation is associated with specific cognitive deficits in individuals with a history of depression and with progressively worsening working memory over time. Adolescents who participated in a prospective, longitudinal study of adolescent-onset depression were recruited to complete a follow-up cognitive assessment. The sample was comprised of 82 participants (52.4% female; 37.8% white; 42.7% low socioeconomic status) who were aged 22.61 years (SD = 1.50) at the time of the follow-up cognitive assessment. Prior to the follow-up cognitive assessment, they had completed an average of 6.24 (SD = 1.80) prior annual assessments over 6.24 years (SD = 2.08) as part of the parent longitudinal study in which C-reactive protein (CRP), depressive symptoms, and working memory were assessed repeatedly. First, using linear regression, we tested whether individuals exhibiting inflammation (CRP ≥3 mg/L) at multiple timepoints and a history of likely depression (Children's Depression Inventory ≥19) exhibited differentially worse executive functioning, episodic memory, or psychomotor speed. Second, using hierarchical linear modeling, we tested whether the combination of inflammation and likely past depression was associated with poorer working memory over time. Chronic inflammation was associated with worsening working memory over time, but no significant associations were observed in cross-sectional analyses. These preliminary data indicate that chronic inflammation may lead to progressive decline in working memory over time.

Sex-Specific Pathways From Prenatal Maternal Inflammation to Adolescent Depressive Symptoms.

Importance: Prenatal maternal inflammation has been associated with major depressive disorder in offspring in adulthood as well as with internalizing and externalizing symptoms in childhood; however, the association between prenatal inflammation and offspring depression in adolescence has yet to be examined. Objective: To determine whether maternal levels of inflammatory biomarkers during pregnancy are associated with depressive symptomatology in adolescent-aged offspring and to examine how gestational timing, offspring sex, and childhood psychiatric symptoms impact these associations. Design, Setting, and Participants: This was an observational study of a population-based birth cohort from the Child Health and Development Studies (CHDS), which recruited almost all mothers receiving obstetric care from the Kaiser Foundation Health Plan (KFHP) in Alameda County, California, between June 1959 and September 1966. Pregnancy data and blood sera were collected from mothers, and offspring psychiatric symptom data were collected in childhood (ages 9-11 years) and adolescence (ages 15-17 years). Mother-offspring dyads with available maternal prenatal inflammatory biomarkers during first and/or second trimesters and offspring depressive symptom data at adolescent follow-up were included. Data analyses took place between March 2020 and June 2023. Exposures: Levels of inflammatory biomarkers (interleukin 6 [IL-6], IL-8, IL-1 receptor antagonist [IL-1RA], and soluble tumor necrosis factor receptor-II) assayed from maternal sera in the first and second trimesters of pregnancy. Main Outcomes and Measures: Self-reported depressive symptoms at adolescent follow-up. Results: A total of 674 mothers (mean [SD] age, 28.1 [5.9] years) and their offspring (350 male and 325 female) were included in this study. Higher second trimester IL-6 was significantly associated with greater depressive symptoms in offspring during adolescence (b, 0.57; SE, 0.26); P = .03). Moderated mediation analyses showed that childhood externalizing symptoms significantly mediated the association between first trimester IL-6 and adolescent depressive symptoms in male offspring (b, 0.18; 95% CI, 0.02-0.47), while childhood internalizing symptoms mediated the association between second trimester IL-1RA and adolescent depressive symptoms in female offspring (b, 0.80; 95% CI, 0.19-1.75). Conclusions and Relevance: In this study, prenatal maternal inflammation was associated with depressive symptoms in adolescent-aged offspring. The findings of the study suggest that pathways to adolescent depressive symptomatology from prenatal risk factors may differ based on both the timing of exposure to prenatal inflammation and offspring sex.

Ethnoracial Risk Variation Across the Psychosis Continuum in the US: A Systematic Review and Meta-Analysis.

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.

Comparing a Computerized Digit Symbol Test to a Pen-and-Paper Classic.

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.

The influence of psychotic-like experiences on intent to seek treatment: Findings from a multi-site community survey of mental health experiences.

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.

Working memory performance is related to childhood trauma but not psychotic-like experiences in a nonpsychiatric sample.

OBJECTIVE: This project seeks to clarify the impact of childhood trauma and psychotic-like experiences (PLEs) on working memory (WM) and explore gender differences in these relationships. The effect of childhood trauma on WM performance has yet to be explored in individuals with PLEs, despite consistent associations between trauma, psychosis spectrum symptoms, and WM performance. METHOD: In 466 undergraduates, positive PLEs (Prodromal Questionnaire) and trauma (Childhood Trauma Questionnaire) were examined to determine contributions to WM performance on a spatial n-back task. We conducted hierarchical linear regressions on the total sample and stratified by gender to examine the effects of childhood trauma, positive PLEs, and their interaction on WM performance. Supplemental analyses explored attenuated negative and disorganized symptoms. RESULTS: Controlling for age, there were no significant main effects of positive PLEs, childhood trauma, their interaction, or three-way interaction including gender in predicting WM. After stratifying by gender, childhood trauma was significantly associated with poorer WM in females only. Post hoc analyses revealed that in the full sample, physical neglect predicted WM performance and was a trend for females, while sexual abuse trended toward predicting WM in males. Supplemental analyses of attenuated negative and disorganized symptoms revealed childhood trauma significantly predicted WM in the full sample and females only for negative symptoms. CONCLUSIONS: Females who have experienced childhood trauma may be at greater risk for WM problems, irrespective of co-occurring PLEs, suggesting that cognitive difficulties may be partially attributable to history of trauma. These findings have potential implications for intervention strategies in trauma-exposed individuals. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Reward and Immune Systems in Emotion (RISE) prospective longitudinal study: Protocol overview of an integrative reward-inflammation model of first onset of major depression in adolescence.

Background: Depression is associated with a reduced sensitivity to rewards and low reward-related brain function in cortico-striatal circuitry. A separate literature documents elevated peripheral inflammation in depression. Recently, integrated reward-inflammation models of depression have been proposed. These models draw on work indicating that peripheral inflammatory proteins access the brain, where they lower reward responsiveness. This blunted reward responsiveness is proposed to initiate unhealthy behaviors (substance use, poor diet), as well as sleep disruption and stress generation, which further heighten inflammation. Over time, dysregulation in reward responsiveness and immune signaling may synergize in a positive feedback loop, whereby dysregulation in each system exacerbates dysregulation in the other. Project RISE (Reward and Immune Systems in Emotion) provides a first systematic test of reward-immune dysregulation as a synergistic and dynamic vulnerability for first onset of major depressive disorder and increases in depressive symptoms during adolescence. Methods: This NIMH-funded R01 study is a 3-year prospective, longitudinal investigation of approximately 300 community adolescents from the broader Philadelphia area, United States of America. Eligible participants must be 13-16 years old, fluent in English, and without a prior major depressive disorder. They are being selected along the entire dimension of self-reported reward responsiveness, with oversampling at the low tail of the dimension in order to increase the likelihood of major depression onsets. At Time 1 (T1), T3, and T5, each a year apart, participants complete blood draws to quantify biomarkers of low-grade inflammation, self-report and behavioral measures of reward responsiveness, and fMRI scans of reward neural activity and functional connectivity. At T1-T5 (with T2 and T4 six months between the yearly sessions), participants also complete diagnostic interviews and measures of depressive symptoms, reward-relevant life events, and behaviors that increase inflammation. Adversity history is assessed at T1 only. Discussion: This study is an innovative integration of research on multi-organ systems involved in reward and inflammatory signaling in understanding first onset of major depression in adolescence. It has the potential to facilitate novel neuroimmune and behavioral interventions to treat, and ideally prevent, depression.

Development of the PSYCHS: Positive SYmptoms and Diagnostic Criteria for the CAARMS Harmonized with the SIPS.

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

Development and Validation of the Negative Symptom Inventory-Psychosis Risk.

BACKGROUND AND HYPOTHESES: Early identification and prevention of psychosis is limited by the availability of tools designed to assess negative symptoms in those at clinical high-risk for psychosis (CHR). To address this critical need, a multi-site study was established to develop and validate a clinical rating scale designed specifically for individuals at CHR: The Negative Symptom Inventory-Psychosis Risk (NSI-PR). STUDY DESIGN: The measure was developed according to guidelines recommended by the NIMH Consensus Conference on Negative Symptoms using a transparent, iterative, and data-driven process. A 16-item version of the NSI-PR was designed to have an overly inclusive set of items and lengthier interview to support the ultimate intention of creating a new briefer measure. Psychometric properties of the 16-item NSI-PR were evaluated in a sample of 218 CHR participants. STUDY RESULTS: Item-level analyses indicated that men had higher scores than women. Reliability analyses supported internal consistency, inter-rater agreement, and temporal stability. Associations with measures of negative symptoms and functioning supported convergent validity. Small correlations with positive, disorganized, and general symptoms supported discriminant validity. Structural analyses indicated a 5-factor structure (anhedonia, avolition, asociality, alogia, and blunted affect). Item response theory identified items for removal and indicated that the anchor range could be reduced. Factor loadings, item-level correlations, item-total correlations, and skew further supported removal of certain items. CONCLUSIONS: These findings support the psychometric properties of the NSI-PR and guided the creation of a new 11-item NSI-PR that will be validated in the next phase of this multi-site scale development project.

Self-reported Gesture Interpretation and Performance Deficits in Individuals at Clinical High Risk for Psychosis.

BACKGROUND AND HYPOTHESIS: Deficits in performing and interpreting communicative nonverbal behaviors, such as gesture, have been linked to varied psychopathology and dysfunction. Some evidence suggests that individuals at risk for psychosis have deficits in gesture interpretation and performance; however, individuals with internalizing disorders (eg, depression) may have similar deficits. No previous studies have examined whether gesture deficits in performance and interpretation are specific to those at risk for psychosis. Additionally, the underlying mechanisms (eg, cognition) and consequences (eg, functioning) of these deficits are poorly understood. STUDY DESIGN: This study examined self-reported gesture interpretation (SRGI) and performance (SRGP) in those at clinical high risk for psychosis (CHR; N = 88), those with internalizing disorders (INT; N = 51), and healthy controls (HC; N = 53). Participants completed questionnaires, clinical interviews, and neurocognitive tasks. STUDY RESULTS: Results indicated that the CHR group was characterized by significantly lower SRGI scores than the HC or INT groups (d = 0.41); there were no differences among groups in SRGP. Within CHR participants, greater deficits in SRGP were associated with lower verbal learning and memory (r = -.33), but not general intelligence or processing speed. Furthermore, gesture deficits were associated with higher cross-sectional risk for conversion to a full psychotic disorder in the CHR group. CONCLUSIONS: Overall, these findings suggest that specific subdomains of gesture may reflect unique vulnerability for psychosis, self-report may be a viable assessment tool in understanding these phenomena, and gesture dysfunction may signal risk for transition to psychosis.

The reliability and validity of the revised Green et al. paranoid thoughts scale in individuals at clinical high-risk for psychosis.

INTRODUCTION: Paranoia is a common and impairing psychosis symptom, which exists along a severity continuum that extends into the general population. Individuals at clinical high-risk for psychosis (CHR) frequently experience paranoia and this may elevate their risk for developing full psychosis. Nonetheless, limited work has examined the efficient measurement of paranoia in CHR individuals. The present study aimed to validate an often-used self-report measure, the revised green paranoid thoughts scale (RGPTS), in this critical population. METHOD: Participants were CHR individuals (n = 103), mixed clinical controls (n = 80), and healthy controls (n = 71) who completed self-report and interview measures. Confirmatory factor analysis (CFA), psychometric indices, group differences, and relations to external measures were used to evaluate the reliability and validity of the RGPTS. RESULTS: CFA replicated a two-factor structure for the RGPTS and the associated reference and persecution scales were reliable. CHR individuals scored significantly higher on both reference and persecution, relative to both healthy (ds = 1.03, 0.86) and clinical controls (ds = 0.64, 0.73). In CHR participants, correlations between reference and persecution and external measures were smaller than expected, though showed evidence of discriminant validity (e.g., interviewer-rated paranoia, r = 0.24). When examined in the full sample, correlation magnitude was larger and follow-up analyses indicated that reference related most specifically to paranoia (ß = 0.32), whereas persecution uniquely related to poor social functioning (ß = -0.29). CONCLUSION: These results demonstrate the reliability and validity of the RGPTS, though its scales related more weakly to severity in CHR individuals. The RGPTS may be useful in future work aiming to develop symptom-specific models of emerging paranoia in CHR individuals.

Review of factors resulting in systemic biases in the screening, assessment, and treatment of individuals at clinical high-risk for psychosis in the United States.

Background: Since 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. Results: Existing 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. Conclusions: Collectively, 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.

The Impact of Early and Recent Life Stress on Trajectories of Inflammatory Biomarkers in a Diverse Sample of Adolescents.

Elevated inflammatory activity is one possible pathway through which exposure to childhood adversity engenders risk for physical and psychiatric illnesses. Limited research has investigated the compounding effects of childhood and adolescent stress exposure on changes in circulating levels of inflammatory biomarkers. This study assessed whether childhood adversity interacted with chronic or acute stress during adolescence to affect the temporal trajectories of five inflammatory biomarkers across at least three blood draws in a diverse sample of adolescents (N = 134; observations = 462). Using multilevel modeling, the interaction of childhood adversity, time, and within-person variance of acute stressors significantly predicted trajectories of higher interleukin-10 levels, controlling for demographics, medication use, and body mass index. Adolescents with high levels of childhood adversity who were exposed to a higher frequency of acute stressors compared to their own average rate of stress exposure consistently had higher levels of IL-10 as they got older, but those with average and below frequency of acute stressors had decreasing trajectories of log IL-10 as they matured. The results demonstrate how events early in life shape biological responses to the adolescent environment. This study also highlights the importance of developmental timing on the body's enhanced reactivity to acute and sustained stressors following childhood adversity.